Electrospinning And Nanofibers - Building Drug Delivery Systems And Potential In Pesticide Delivery (Wenjie Shangguan).Pdf

Electrospinning and nanofibers Building drug delivery systems and potential in pesticide delivery Materials Today Communications 33 (2022) 104399 Available online 8 September 2022 2352 4928/© 2022 Els[.]

Available online 8 September 2022

2352-4928/© 2022 Elsevier Ltd All rights reserved

Electrospinning and nanofibers: Building drug delivery systems and

potential in pesticide delivery

aEngineering Research Center of Pesticide of Heilongjiang Province, College of Advanced Agriculture and Ecological Environment, Heilongjiang University, 150080

Harbin, China

bKey Laboratory of Integrated Pest Management in Crops, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, 100193

Beijing, China

cHeilongjiang Plant Quarantine and Protection Station, 150080 Harbin, China

A R T I C L E I N F O

Keywords:

Electrospinning

Nanofiber

Drug release system

Nanoformulation processing

Controlled release

A B S T R A C T Flexible and efficient electrospinning technology is favored in pharmaceutical processing Nanocarriers obtained

in this way have high drug loading capacity, encapsulation, and excellent mechanical properties, thus enriching the equipment library of drug delivery systems It is also noteworthy that the superior performance of nanofiber carriers has attracted the attention of the pesticide nanoformulation field, this technology is gradually promoting pesticide delivery systems moving to the nanoscale, which will increase the application scenarios and safety of traditional pesticides It is a mainstream trend to obtain multi-structured fiber carriers at the microscopic level through needle modification of electrospinning equipment In this paper, electrospinning technology and elec-trospun nanofiber are introduced in detail, included drug nanocarriers and multiple electrospinning methods, these are necessary and comprehensive for the expansion and translation of nanotechnology applications More importantly, the development and challenges of electrospinning in pesticide micro/nano formulation are reviewed, and prospects were also prospected from the perspective of nanoscale pesticide formulation processing and application, all to improve the combination of electrospinning nanotechnology and plant protection

1 Introduction

Drug delivery systems can solve the traditional drug dilemma [1–5]

The use of polymers as drug delivery vehicles can provide practical

properties such as controlled and sustained release, enhancement and

protection of drug activity, safety, and others, besides studies have

shown that these composite systems can be effective in clinical

treat-ment [6] The developtreat-ment of carrier materials down to the nanoscale

further enhances the targeting and intracellular penetration of the

complexes and allows for continuous circulation in the body, improving

the overall therapeutic effect of the enhanced delivery mechanism [7,8]

Stimulus-responsive nanocarriers can also make drug delivery systems

more intelligent and flexible for different therapeutic scenarios, and

nanocarrier-assisted drug delivery systems are rapidly becoming a

research hotspot [9] Initially, a template method based on "membrane

synthesis" allowed for size-controlled nanofiber carriers to be obtained

[10] Nanofibers have the advantages of small diameter, high porosity,

large specific surface area, and mechanical properties compared to

conventional fibrous materials [11] Thus, these properties allow nanofibers to be used with a wide range of drugs and in novel drug delivery systems However, the question of how to improve the prepa-ration efficiency and average product quality of nanocarriers to reach the standard of scale-up and industrialization has been one of the most pressing problems for researchers and nano companies

Electrospinning is a flexible, efficient, homogeneous uniform nano-fiber preparation technology that has largely improved the productivity

of the nano-pharmaceutical industry [12] In fact, in the last two de-cades, more and more researchers have been focusing on the preparation

of drug nanocarriers by electrospinning technology and have achieved remarkable results Electrospinning compounding of pure drug mole-cules with polymers results in drug delivery systems with a sustained release effect [13] The electrospun fibers of artemisinin complexes with core-shell structures for effective transdermal drug delivery systems [14] Improved triaxial electrospinning provides a more optimal de-livery mode for aspirin drugs [15] Unconventional air-jet electro-spinning technology enables efficient access to protein carrier-based

* Corresponding authors

E-mail addresses: shanggwj@126.com (W Shangguan), caolidong@caas.cn (L Cao), 2016048@hlju.edu.cn (Z Wang), xuhongliang@hlju.edu.cn (H Xu)

Contents lists available at ScienceDirect Materials Today Communications journal homepage: www.elsevier.com/locate/mtcomm

https://doi.org/10.1016/j.mtcomm.2022.104399

Received 12 May 2022; Received in revised form 18 August 2022; Accepted 5 September 2022

nanofiber meshes [16] These studies have shown the limitless value of

this technology in the preparation of drug nanocarriers To be sure, it is

also a technology worthy of continuous development Today,

applica-tions relating to electrospinning technology have been involved in a

wide range of fields, such as medicine, food, clothing, and others

[17–19] (Fig 1)

It is also worth noting that traditional agriculture is facing the double

challenges of inadequate supply and serious pollution therefore the

agricultural sector must undergo a comprehensive energy transition and

structural optimization [20] Likewise, the world is focusing on the

impact of pesticides as a guarantee of agricultural production on the

future of sustainable agriculture [21] As nanotechnology and

nano-materials enter agricultural production, they will largely contribute to

the overall transformation of green pesticides, of which electrospinning

has attracted the interest of some researchers with its superior

perfor-mance [22–25] In this review, the purpose is to gain insight into the

development and integration of electrospinning technology with drug

nanocarriers and to further explore the impediments and future of this

technology in the preparation of pesticide carriers, which we hope will

stimulate the reader’s thinking

2 Nanocarriers

Nanoparticles are often defined as ultrafine particles with a particle

diameter between 1 and 100 nm Nanomaterials are materials with

di-mensions up to nanometer size in at least one dimension of three-

dimensional space, and can usually be divided into three categories:

[10,26–28] (1) the first category is in the form of nanoparticles,

nano-wires, or nanotubes; (2) the second category is nanolayers or nanofilms;

(3) the third category is nanospheres or nanoflowers A set of different

tests have shown that these materials on the nanoscale possess unique

electrical, optical, mechanical, and magnetic properties [29] Chitin and

chitosan are very popular drug carrier materials in recent years Their

variation on this nanoscale is very surprising, as their various biological

properties are enhanced with the increase in effective surface area, and

material properties such as antibacterial, antioxidant, thermal, and

mechanical properties become more prominent, with the consequent

benefit of a wider range of applicability [30]

As the recognition of nanoparticles and nanotechnology increases,

increasingly different applications are being developed In the middle of the 20th century, the use of nanotechnology began to explode, and na-tional research institutes were established to develop nanotechnology [31] In the same period, the advances in biopharmaceutics and phar-macokinetics focused the attention of researchers on the controlled and sustained release of drugs [32] The first nanocapsules for drug delivery were developed in the 1970 s and this work succeeded in prolonging the release time of drugs [33] Since then, drug nanocarriers have officially entered the limelight

Nanocarriers often refer to new carriers with a particle size between

10 and 1000 nm, and the materials of nanocarriers are inorganic nanomaterials (carbon, fullerene derivatives, metals, and metallic ox-ides, porous materials) and organic nanomaterials (natural bio-molecules, synthetic polymers, semi-synthetic polymers) [28,34] These materials can be processed for use in exogenous stimuli-responsive drug delivery (temperature, magnetic, ultrasound, light, and electrical sensing) and endogenous stimuli-responsive drug delivery (pH, redox, enzymes) as well as multi-stimuli-responsive drug delivery [35,36] In addition, drug delivery systems are often expected to have the following characteristics to adapt to different therapeutic conditions or environ-ments [7,37]: (1) long-term cycle; (2) targeted drug delivery through multiple mechanisms of action; (3) stimulation in response to patho-logical location; (4) enhanced drug delivery through the intracellular movement of drug molecules; (5) provided real-time information on drug biodistribution and target accumulation These characteristics are strongly associated with cellular internalization mechanisms [38] When engineered nanocarriers of the appropriate size class are designed, delivery of sustained-release drugs can be achieved in a va-riety of situations [39–41] The methods typically used to prepare nanomedicine carriers: pre-polymerization, monomer polymerization, and ionic gelation [28,42–44] The conventional carriers prepare by pre-polymerization method suffers from poor encapsulation and low drug loading, while solvents and additives in the preparation process are difficult to handle completely, which can have an impact on later drug toxicity and therapeutic effects When preparing drug nanocarriers by monomer polymerization, most samples suffer from poor mechanical and thermal properties The ionic gelation process is highly restrictive and difficult to put into large-scale industrial production However, the research has shown that nanofibers prepared by electrospinning have a

Fig 1 Electrospinning technology for different applications

high drug loading capacity with low toxicity, excellent thermodynamic

properties, better industrial value, and powerful encapsulation

capa-bilities, so electrospinning technology is emerging as an excellent

alternative technology [45–49]

3 Electrospinning and nanofibers

Electrospinning was officially born in the 1930 s, Anton [50]

suc-cessfully applied for a patent for electrospinning, after which nanofiber

preparation, a symbol of efficiency and convenience, was officially

introduced into human society After then Childs et al [51] improved

the processing apparatus of electrospinning, effectively solving the

problems of extrusion of polymers and their derivatives, continuous

extrusion, and extrusion efficiency In 1969, Taylor et al [52] analyzed

in detail the process of cone formation (Taylor cone) of droplets at the

end of the needle and the ejection process of the fiber stream, which

helped further understanding of how electrospinning machines work

Subsequently, HOW et al [53] used electrospinning to synthesize

polymeric materials into artificial vascular grafts Gilding et al [54]

used electrospinning to produce homogeneous porous nonwoven fiber

mats Hence, the application of electrospinning technology has been

extended to drug delivery systems in the medical field {{{Fig 2}}}

Electrospinning technology works by using a high voltage power

supply to bring a charge of a certain polarity into the polymer solution or

melt After the charge has been accelerated into the collector at the

opposite electrode it is subject to electrostatic attraction and internal

repulsion of the solution When the electric field force is greater than the

surface force, the semi-circular tip becomes a cone, and the fibers stream

is then ejected from the cone tip Finally, passing through the

atmo-sphere where the solvent evaporates and is eventually deposited on the

grounded collector [56] After mathematical analysis of the motion of a

single fiber in a uniform and non-uniform electric field, it was found that

the output of an electrostatic spinning machine was more than 20 times

higher than that of a traditional spinning machine by a staggering

margin [57] When comparing electrospray and electrospun, which are

polymer processing processes, obvious differences in sample properties

and processing parameters were found After the preparation of

micro-spheres and fibers containing different concentrations of caffeine by

both methods, the electrospun produced better yields and morphology,

and the in vitro drug release of nanofibers was found to be better than

that of nanospheres [58,59]

When drug nanocarriers are prepared by electrospinning, the

morphology of the nanofibers is often a combination of different

ele-ments [60] The crucial elements are the feedstock properties, the

process parameters of the spinning machine, and environmental con-ditions [56,61,62] In Table 1, the effect of process parameters, solution parameters, ambient parameters on fiber morphology were summarized

As understanding of the nature of drug carriers and the principles of the electrospinning process grows, more drugs are using electrospun fiber as carriers which are used in different therapeutic scenarios For example, gentamicin sulfide [70], doxycycline [71], curcumin [72], ciprofloxacin [73], hyaluronic acid [74], moxifloxacin [75], silver nanoparticles [76], etc are used in fiber-based treatments Typically, idealized electrospinning produces continuous nanofibers of uniform diameter, defect-free morphology, and individually collectible fibers [77] However, the properties of different drugs can affect the overall compounding system and the electrospinning process The physico-chemical properties of nanofibers will have an important impact on the drug delivery system as can be seen from numerous research reports [78–80] Among them, it has been shown that the selection of the right type of carrier material, electrospinning method, and additives will optimize the mechanical properties, hydrophilic, antimicrobial proper-ties, and other key physicochemical properties of nanofibers [81–83] The superiority of nanofibers in terms of physicochemical properties is illustrated by the results of some of the studies listed in Table 2

4 Diversified electrospun fibers

The release mechanism of nanofiber drug delivery systems prepared

by electrospinning can be divided into three controlled phases, in order

of diffusion due to fiber swelling, release through the membrane, and polymer degradation, with significant differences in the rates of the

Fig 2 A brief Schematic representation of the electrospinning process and its relevant parameters

Adapted with permission from [55] Copyright 2014 American Chemical Society

Table 1

Table of parameters affecting fiber morphology

Category Parameter Effect on fiber Reference processing applied voltage diameter; morphology [63]

flow rate/feed rate size; porosity; shape [64] tip to collector distance diameter; morphology [65] orifice diameter diameter; morphology [61] types of collectors structure [62] feedstock concentration diameter; morphology [56]

viscosity diameter; morphology [66]

solvent dielectric constant diameter [68] ambient temperature diameter; morphology [69]

three phases [102] Specific drug delivery methods include (1) physical

absorption of the drug by the nanofiber, with the drug mostly dispersed

on the carrier surface; (2) chemical surface modification of the fibers; (3)

mixing of the drug and polymer solution and spinning in emulsion form;

(4) preparation of drug/nanofibers with core-shell or multilayer

struc-tures by coaxial or multi-axial electrospinning techniques [103]

The most common methods for the preparation of drug carriers by

the electrostatic spinning devices are mono-axial electrospinning and

coaxial electrospinning, while coaxial electrospinning can produce nanofibers with a core-shell structure [104] In recent years, in order to meet the needs of new drug delivery systems, a multi-fluid electro-spinning process has been obtained by changing the needle of the de-vice, which enables more composition and spatial structure of the drug delivery systems [105] In addition, the use of side-by-side electro-spinning to obtain Janus nanofibers with asymmetric properties has also attracted the attention of scientists [106] In recent years, scholars have

Table 2

Physicochemical properties of nanofibres obtained by electrospinning

Physicochemical

properties Carrier material Additive Combination method Optimized performance and data Application Reference Mechanical

performance PLA/GO Silver nanoparticle Blend electrospinning Tensile stiffness and strength (1211.05 MPa and 5.46 MPa) Tissue-engineering scaffolds [76]

PLGA /ALG Ciprofloxacin Blend electrospinning Young’s modulus and tensile strength

(approx 150 MPa and 4.5 MPa) Wound dressing [73] PLA Doxycycline Blend electrospinning Ultimate tensile strength (5.57 ± 0.43 MPa) Wound dressing [71] PVA/PLGA Gentamicin/

Methylprednisolone Blend/ Double-jet/ Coaxial

electrospinning

Folding endurance (142–430 times) Ophthalmic drug

delivery [84] PVA/ HPβCD Hyaluronic acid/

Naproxen Blend electrospinning Young’s modulus in dry state (609 ± 360 MPa), Strain at fracture in the water state

(127 ± 11 %)

Tissue-engineering scaffolds [74] PVP Metronidazole Blend electrospinning Work of mucoadhesion (4830–1560 mJ/

Chitosan /CS/PUL Norfloxacin/

Montmorillonite Blend electrospinning Elongation in the dry state (approx 49%) Tissue-engineering scaffolds [86] PLGA/Gel Pluronic F127/

Prodigiosin Blend electrospinning Young’s modulus and ultimate tensile strength (1.290 ± 0.617 kPa and 0.185 ±

0.480 kPa)

Tissue-engineering scaffolds [87] Hydrophilic PBAT Gentamicin Blend electrospinning Water contact angle (from 127◦to 0◦) Wound dressing [88]

Fish gelatin Caffeine Blend electrospinning Disintegration time (1.5 seconds) Fast-disintegrating

drug delivery systems

[89]

PLA/PU Tannic acid/ Silver

nanoparticles Blend electrospinning/ LBL self-assembly Water contact angle (from 121

◦to 78.9◦) Antibacterial

dressing [90] Chitosan /PVA/GO Allicin Blend electrospinning Water contact angle (from 65◦to 53.4◦) Wound dressing [91] Chitosan /Gel/ PEO Hyaluronic acid Double-jet

electrospinning/ Water vapor treatment

Water contact angle (from 54◦to 41◦) Wound dressing [92]

PCL/PEO Doxycycline Blend electrospinning Water contact angle (from 115.35◦to 0◦) Drug delivery

Antimicrobial

properties PEO/CS Moxifloxacin Blend electrospinning The corresponding radius of the zone of inhibition (mean ± SD) Againsting

S aureus, E coli, and P aeruginosa (32.33 ±

1.15 mm, 35.67 ± 1.53 mm, and 36.83 ± 2.56 mm)

Tissue-engineering scaffolds [75]

PVA/CH Tetracycline

hydrochloride Blend electrospinning The corresponding radius of the zone of inhibition (mean ± SD) Againsting E coli,

S epidermidis, S aureus (8.8 ± 0.4 mm, 15.6

±0.3 mm, and 19.6 ± 0.2 mm)

Topical delivery platform [94]

PEO/ALG Vancomycin Blend electrospinning The corresponding radius of the zone of

inhibition (mean ± SD) Againsting MRSA (approx 13 mm)

Wound dressing [95]

Starch/PEO Silver nanoparticles Blend electrospinning/

In situ reduction The corresponding radius of the zone of inhibition (mean ± SD) Againsting E coli

and S aureus (more than 9.7 mm and more

than 10.2 mm)

Wound dressing [96]

PEG/PCL Silver

nanoparticles/

Hyaluronic acid/

Ibuprofen

Coaxial electrospinning Zone of inhibition measurements against E coli and S aureus (0.24 ± 0.07 cm2 and

0.18 ± 0.09 cm2)

Multifunctional barrier membrane [97]

Chitosan /Gel Cinnamon extract Blend electrospinning Antibacterial activity against E coli and

S aureus (82 ± 5 % and 90 ± 6 %) Medical material [98]

Allyl-TPU Quaternary

ammonium compounds

Multinozzle blend electrospinning After in contact with E coli and S aureus for 15 min (UV-treated), approx 35% killing

against E coli and approx 60% killing against S aureus

Wound dressing [99]

Chitosan/

Polyethylene/5- chloro-8-quinolinol

Poly (hexamethylene biguanide) /Nylon-

6

Coaxial electrospinning The corresponding radius of the zone of inhibition (mean ± SD) Againsting

S aureus and P aeruginosa (14.4 ± 0.7 mm

and 9.9 ± 0.7 mm)

Surgical mesh surfaces [100]

Chitosan /PVA Indocyanine green Blend electrospinning Vlable Colony Count of Pseudomonas

aeruginosa/Staphylococcus aureus (CFU/mL)

Nanofiber: approx 7; Model: approx 8.3

Wound dressing [101]

obtained many different fibers based on a processing-structure-property

preparation concept and modifying the needle structure of

electro-spinning apparatus to obtain nanofiber carriers with different properties

is almost certain to be one of the most common development directions

in the field of carriers in the future {{{Fig 3}}}

4.1 Mono-axial electrospinning

The use of single-needle electrospinning is the original method of

electrospinning, which produces fibers with continuity, toughness, high

porosity, and mechanical properties Surprisingly, it performs well in

terms of productivity and drug delivery [107] In terms of obtaining a

sustained release of the drug, the linezolid combination prepared by this

technique has long-lasting antibacterial activity and can be obtained in a

more stable drug form [108–110] The electrospun fiber mats had

excellent encapsulation rates and mechanical properties [111] Drug

carriers were able to perform the long-term treatment at low drug doses

In subsequent studies, researchers found that different solvents and even

different solvent ratios affected the spinnability of the solution in the

process, so the resulting slow release of the drug was different [112] In

another case, Bohm et al [113] postulated that viscosity-induced

changes in spinnability might be due to chemical reactions or physical

entanglements that form crosslinks in the feedstock

The advantages of mono-axial electrospinning technology are also

reflected in the high encapsulation and loading capacity For example,

essential oil requires a closed environment for the delivery and the fiber

structure provides an effective encapsulation for these drugs, thus

extending their range of application [114–117] In the delivery system

loaded with essential oils, the antimicrobial effect becomes more

pro-nounced over time and the essential oils are well protected, resulting in a

surprisingly slow release [118,119] Comparing different preparation

techniques for drug carriers, Karen et al [120] evaluated microcapsules

and nanofiber films loaded with cinnamaldehyde and tested them

spe-cifically for their encapsulation and antifungal properties The results

indicated that the fiber carrier prepared by the single-needle

electro-spinning technique was able to encapsulate about 0.4 g of

cinnamalde-hyde and had a wider area of inhibition against the grey mold fungus At

the same time, low-cost single-needle electrospinning is also a very

promising way to prepare fast-dissolving tablet formulations on the

market [121,122] Solubilization ability of porous nanofibrous supports has been verified [123–125] In recent years, with the improvement of mono-axial electrospinning machines, the production speed has been greatly enhanced and the related downstream production lines have been intensively developed [126–129] Szabo et al [130] prepared electrospun tablets loaded with itraconazole and designed a continuous system to produce pharmaceutical formulations, drug testing, and product collection, this system provides a reference for tablet prepara-tion of poorly soluble pesticides

4.2 Side-by-side electrospinning

By adapting the needle structure of the electrospinning apparatus so that the solution enters the needle from both sides and is then electro-spinning, it can obtain Janus nanofibers Drug carriers prepared by side- by-side electrospinning provide a stable two-stage drug release mecha-nism, one stage leads to an accelerated release with increased drug dissolution and the other gives a sustained and controlled release for the drug in the polymer [131] Materials with opposite properties are widely used in side-by-side electrospinning to gain more functionality [132–137] In a study by Zheng et al [138], it seems possible that for water-soluble polymers, the crescent shape facilitated rapid release while the round shape facilitated the controlled and sustained release of the composite drug It is quite certain that the concept of functional nanomaterials design based on shape change will strike on future thinking about drug production Secondly, to ensure the formation of effective Janus nanofiber structures, the various spin fluids should have sufficient contact time and area before spinning [139] Compared to single-needle electrospinning fibers, fibers with two different sides offer more versatility in design and functionality in special scenarios [106]

In addition, the beading of fibers caused by changes in the drug to polymer ratio during electrospinning has long been regarded as a sign of

a defective product However, Li et al [140] obtained a Janus beads-on-a-string prepared by side-by-side electrospinning technique, and controlled the particle distribution and diameter range of the Janus beads-on-a-string nanostructures by polymer concentration, while the Janus beads-on-a-string obtained a better release than the Janus nano-fiber (Fig 4)

Fig 3 Preparation of drug carriers and their fibrous morphology by electrospinning technology

4.3 Coaxial electrospinning

The coaxial electrospinning apparatus has two concentric nozzles

that eject fibers with a core-shell structure under voltage This

tech-nology, which was first proposed in experiments with water

encapsu-lation, has surprisingly attracted a lot of attention and the encapsulation

and protection offered by the core-shell fibers have unlimited potential

in the field of drug delivery [141–143]

The core is better protected by the shell material of the coaxial

electrospun fibers, coaxial electrospinning technology have been proven

to have outstanding drug release [144,145] Rafiei et al [146] combined

wet electrospinning and coaxial electrospinning to produce a

tissue-engineering scaffold with a three-dimensional “spongy” structure

It has commonly been assumed that the porous structure of the

nano-fibers facilitates the proliferation of cells or the efficient release of active

substances Environmentally responsive polymers could provide

addi-tional targeting capabilities when used as carrier material Wang et al

[147] developed a multi-component nanofiber that could control drug

release based on pH changes, thereby enabling multi-point drug release

Indeed, the improved coaxial electrospinning apparatus also enables

electrospinning of traditionally "non-spinnable" solutions and is one of

the potential techniques for the formation of amorphous solid

disper-sions (Fig 5) [148–151] It has been reported that the stable Taylor cone

could be a key factor in the formation of this core-shell structure [152]

Finally, because of the encapsulation properties of the core-shell

struc-ture, the drug rarely appears on the surface of the fibers and thus the

coaxial electrospinning technology could effectively inhibit the side ef-fects of sudden drug release [13,153] The core-shell structural response function can also be achieved by processing pH-sensitive materials [154]

4.4 Triaxial electrospinning

The triaxial electrospinning technology changes the needle structure since the traditional electrospinning apparatus and introduces three fluids together for electrospinning, thus obtaining multi-layered nano- fiber mats The fibers prepared by triaxial electrospinning can have more structural and hierarchical properties, triaxial electrospinning-based fi-bers also play an important role in increasing drug dissolution, sustained release, and zero-order release kinetics, among other functions [155, 156]

Chang et al prepared electrospun shell-Janus core nanostructures for drug delivery, which are capable of intelligent three-stage controlled drug release according to pH changes in the digestive system (Fig 6) [157] In the same way, Ding et al [15] modified the original "dynamic atomization process" by placing the outermost layer of the needle as a solvent layer, resulting in the same functional nanofibers with a core-shell mechanism Nanofibers obtained by triaxial electrospinning have a drug release profile that is closer to the zero-level release kinetics Wang et al [158] utilized cellulose acetate as the sole matrix to prepare drug composite fiber The drug/polymer composite structure of the interlayer allowed for optimization of the diffusion mechanism, which

Fig 4 Preparation and morphology of Janus beads-on-a-string, and schematic diagram of the release mechanism

Reprinted with permission from [140] Comply with Creative Commons Attribution 4.0 International License

in turn eliminated abrupt release and reduced the late tailing-off release

Similarly, Huang et al [159] and Yang et al [160] also constructed

core-shell nano depots based on triaxial electrospinning technology to

optimize the release profile of drugs In order to respond to the needs of

drug delivery in different contexts, electrospinning technology has been

continuously optimized to obtain various functional drug carriers, these

results would seem to suggest that the processing-structure-property

based preparation concept has been more widely accepted

Thus far, this thesis has argued that utilization of electrospinning for

the preparation of drug carriers in the medical field already has some

conditions to enter scale-up and industrialization, and the excellent

properties of nanofibers provide a template for drug delivery that can be

replicated Moreover, how to extend the technology of preparing drug

carriers by electrospinning to pesticide delivery and to create value for

pesticide industry remains one of the key issues for future researchers of

this technology

5 Electrospinning and pesticides

As was pointed out in the introduction to this paper, the high

dependence of traditional agriculture on fossil fuels and the overall lack

of food supply is hindering the transition to sustainable agricultural

development [20] Pesticides, which have been used for phytochemical

protection since ancient times, are one of the main targets of these

doubts The rapidly growing use of pesticides and the difficulty of

sys-tematically regulating the pesticide market have placed a serious burden

on the environment and governments around the world [21] In addition

to groundwater, soil, and food contamination caused by pesticide

misuse, which is difficult to fully address, more and more plant

patho-gens, pests and weeds are showing varying degrees of resistance to

traditional pesticides [161] Meanwhile, the development of new

pes-ticides faces multiple thresholds of toxicology, pathology, and

signifi-cant capital investment (Fig 7) [162]

In recent years, as nanotechnology continues to be introduced into

the agricultural sector, it offers an opportunity for revolutionary de-velopments in the transformation of traditional agriculture and ecological management [163] In particular, the use of polymeric ma-terials to encapsulate agrochemicals, allows them to be applied in a way that is permeable, rigid, biocompatible, and multifunctional in line with the requirements of future green pesticide [22,23,164] Green pesticide

is an important topic worldwide, and its innovation requires new for-mulations for synergy Electrospun nanofibers may make a strong contribution to it in the following aspects:

(1) Natural polymer materials such as chitosan, cellulose, cyclodex-trin, and synthetic polymer materials such as poly-hydroxybutyrate and polycaprolactone have been successfully applied with electrospinning technology [30] These materials with good biodegradability are very friendly and green to the environment Electrospun nanofibers prepared from these mate-rials will be more favored in the development of green carriers for pesticide In addition, this will increase the frequency of appli-cation of biodegradable materials in green pesticides and reduce the burden on the environment from the use of pesticides (2) Electrospun nanofibers provide good mixing chambers for active ingredients, carrier materials, and other functional additives The electrospun carrier possesses high loading and encapsulation ef-ficiency, as well as the large specific surface area brought by the loose porous structure, which can endow the pesticide delivery system with excellent slow and controlled release function [103] This will enhance the effectiveness of pesticides and reduce res-idue problems caused by pesticide abuse

(3) Electrospinning technology can be modified to obtain micro/ nanofibers with different structures, which provide more options for pesticide loading [105] Thus, the flexible electrospinning technology can be used as an application-scenario-oriented development process for pesticide formulations Functionalized chambers and abundant fiber interface modifications enable

Fig 5 Core− shell nanodrug containers prepared by coaxial electrostatic spinning machine, which improved the sustained release of water-insoluble curcumin An

Improved coaxial Electrospinning technique for the Preparation of rapid dissolution carriers for insoluble oral drugs

Reprinted with permission from [148] Copyright 2021 American Chemical Society Reprinted with permission from [151] Comply with Creative Commons Attribution 4.0 International License

stimulus-responsive capabilities Such fibers can promote the

precise targeting of pesticides and provide a more scientific and

efficient platform for pesticide delivery

(4) With the development of biotechnology, biopesticides have

become an important part of green pesticides Due to the high

requirements for biological activity of biopesticides,

conven-tional pesticide formulation processing methods cannot be well

applied The microscopic arrangement of electrospun nanofibers

is conducive to the growth of mycelium, and its activity and

persistence are optimized and enhanced [165] The related

technical achievements and crossover fields of electrospinning

may lead the formulation innovation of green pesticide products

The previous section has shown that electrospinning technology in the preparation of drug carriers has formed a certain scale of the research base and theoretical system Fortunately, the successes and lessons learned from this technology in medical drug delivery systems can be transferred to the construction of new pesticide delivery systems and address a number of these pressing issues [166] Nanofiber carriers have been attracted to the utilization of electrospinning technology for agricultural plant protection in the last decade because of their desirable properties such as high specific surface area, drug encapsulation rate, and loading capacity, and controlled and sustained release of drugs Insect pheromones, microbial pharmaceuticals, and some pesticides have been successfully combined with electrospun nanofibers and used

Fig 6 Morphological and internal structural features of sheath-separate-core nanofibers: (a) SEM images of the cross-sections, (b) TEM image of the inner complex

nanostructures (c) Physical status of the components: XRD patterns (the raw polymers, drug and the sheath-separate-core nanofibers), PM image of drug substance particles (d) In vitro drug release profile of sthe sheath-separate-core nanofibers: A-stomach; B-small intestine; C-colon

Reprinted with permission from [157] Comply with Creative Commons Attribution 4.0 International License

Fig 7 The dilemma facing pesticides around the world

in pesticide delivery systems [24,25]

5.1 Insect pheromone

Insect pheromones are regarded as a non-toxic, environmentally

friendly, and species-specific compound and are fastly becoming an

important part of agricultural pest management, enabling the use of

pheromones to interfere with pest biology and to be used in conjunction with traps to kill pests over large areas [167] Hellmann et al [168] reported for the first time the electrospun fibers loaded with pheromone (Z)− 9-dodecyl acetate, which disrupted mating in insects, and showed that the carrier fibers could be loaded with large amounts of pheromone and extended the release effect to several months Following this, studies had been reported combining microcapsules with nanofibers to obtain

Fig 8 (A) Solution preparation and electrospinning process, characterization device and experimental materials (B) Interaction between composite membrane

materials and biomolecules (C1-C3) Inhibitory potential regions of biocomposites against bacteria (M phaseolina; R solani; F oxysporum) (C4-C6) Inhibition of

bacteria by biocomposites on different media (D4-D12) Morphology of the nanofibers of the biocomposite, and a close-up of the microbes in the fibers Reprinted with permission from [176] Copyright 2019 American Chemical Society

hydrophilic and stable pheromone carriers [169] At the time, such

expositions are unsatisfactory because these works did not involve field

trials and the exact model of delivery was still at the conceptual stage, so

it was not known how well it would work in practice

Bisotto-De-Oliveira et al [170] demonstrated that nanofibers loaded

with Trimedlure could lure the male of Ceratitis capitata in field cage

tests They also extracted and synthesized pheromones from Grapholita

molesta and then loaded them onto electrospinning fibers, showing that

the system was able to disrupt Grapholita molesta males for up to five

weeks, and this work confirmed that fiber-loaded pheromones can assist

in trapping pests under field conditions [171] Over time, the market for

pheromones for plant protection has demanded more efficacy and

sta-bility Kikionis et al [172] created a pheromone release system capable

of controlling the amount and rate of drug loading and ensuring the

duration of release under different circumstances It has also been

pro-posed that electrospun fibers loaded with picaridin could be used as

insect-proof clothing, which may provide a reference for the preparation

of long-lasting and durable pheromone carriers [173] However, these

are still some distance away from the real needs of pheromone release

systems in different environments and there is a gap with commercial

pheromones Additionally, they could not achieve the requirements of

intelligent and environmentally friendly drug delivery systems

5.2 Microbial pesticide

Nanofibers loaded with microorganisms are used as an effective

alternative technology in biological formulations, and scholars in the

field of plant protection are already practicing in this direction Spasova

et.al [174] loaded Trichoderma viride spores into chitosan via

electro-spinning technique Spores maintained biological activity and

repro-duction while being able to effectively suppress bacteria after covering

the plant Similarly, Damasceno et al [175] prepared a fiber carrier

loaded with soybean rhizobia and the fiber was able to provide

pro-tection to these rhizobia under fungicide conditions Such approaches,

however, have failed to involve illustrating the mechanism and process

of bacterial inhibition by nanofiber loaded with microorganisms, which

was a prerequisite and guarantee for biochemical products to enter the

biocide market In some subsequent studies, the protective effect of

biochemical agents prepared by electrospinning technology on plants or

seeds has been emphasized, without stressing the potential systemic

bactericidal effect of the composite fibers, which may, of course, be

related to the unstable bactericidal capacity of the microorganisms

themselves (Fig 8) [176,177] Recently De Cesare et.al [178]

investi-gated a soil-based three-dimensional porous fibrous scaffold The ability

of the scaffold to provide better delivery assistance when biochemical

agents were used for fungicidal or insecticidal purposes might excite

more discussion on the mechanism and delivery of such compounded

drugs

5.3 Traditional pesticide

Turning now to traditional pesticides, the processes for the

prepa-ration of electrospun fiber loaded with pesticides have emerged

sporadically, but most work has focused on the sustained release of the

delivery system, whereas in practical application scenarios more

vari-able and targeted delivery methods are needed to complement the

treatment [179] In the construction of sustained and controlled release

delivery of chemical pesticides by electrospinning, Roshani et al [180]

used biodegradable Poly(L-Lactide) to prepare an electrospun

mem-brane loaded with thiram pesticide, and verified that the release

mechanism of thiram pesticide in electrospun nanofibers was Fickian

type Their study showed that fiber shrinkage caused by the annealing

operation changes the release mechanism to Higuchi type, which may be

one of the conventional methods for the modification of pesticide fiber

formulations in the future Thitiwongsawet et al [181] prepared 2,

6-dichloro-4-nitroaniline (DCNA)-loaded film formulations by

electrospinning and solvent casting technique, respectively The microporous structure of electrospun films enables higher cumulative release rates of DCNA than in as-cast films, but the release profiles of the two drug-loaded films are not significantly different It is worth noting that in recent years, essential oils have received more and more atten-tion in the field of pesticide applicaatten-tions because of their safety and antibacterial and anti-insect effects Stramarkou et al [182] used elec-trospun nanofibers to effectively restrain the volatile and prolonged action time of rosemary essential oil This innovative strategy may be introduced into agricultural mulch films and greenhouse films, but field trials and more practical application scenarios need to be further developed Farias et al [183] and Casta˜neda et al [184] both utilized electrospinning technology to prepare nanofibers loaded with fungicides

to coat plant seeds, which provided antibacterial throughout the seed development stage and did not cause negative effects Buchholz et al [185] produced an electrospun film of lianas that acted primarily on the pruning openings of the plants, forming a "wound dressing"-like film wrap that was effective in preventing the appearance of infection after antifungal agent loading Czarnobai et al [186] made a very interesting attempt, they used electrospun fibers to load both insecticides and pheromones and demonstrated that there were no side effects in this way Recent cases reported by Gao et al [187–189] also supports the technology that insoluble pesticide loading by electrospinning These efforts have succeeded in increasing the solubility of insoluble pesticides while maintaining concentration and bacterial inhibition, while signif-icantly reducing the content of organic solvents and thus environmental pollution, providing a green and efficient solution for the preparation of traditional pesticide carriers (Fig 9)

In summary, pesticide-loaded electrospun fibers enable the creation

of multifunctional pesticide delivery systems and have industrial po-tential as well as environmental friendliness In comparison with con-ventional pesticide carriers, electrospinning technology has greatly developed the functionality of pesticide carriers, but there is still a lot of potentials to be explored in the preparation of pesticide nanocarriers via this technology Much of the research in the last decade has also been confined to the laboratory or semi-field state, and many of the results have not yet been deployed in large-scale production, depending of course on the synchronization of the associated downstream processes,

as well as the gap compared to their commercial counterparts But it is almost certain there will be much room for discussion about the com-bination of this technology with pesticide encapsulation in the fasci-nating future research agendas

5.4 Potential research directions

Finally, we note some interesting studies that may contribute to the development of the field in the future In the latest research on elec-trospun films for the remediation of environmental pollution, porous fibrous mats are obtained by modifying the film structure and surface of nanofibrous films using porogenic agents, mesoporous materials, defective structures, etc., these super hydrophilic, highly loaded mats could carry a more rapid release pesticide carrier device and would result in a better release under vibration [190,191] It is likely to provide some reference for solving the current problem of dissolution and deposition of insoluble pesticides In the same way, Amorini et al [192] modified electrospun films to form a deep cavity structure on the surface that could accommodate solute molecules, and the cavity structure was freely regulated by pH to meet the renewable and recyclable nature of the films Up to now, not much attention has been paid to recyclable electrospinning carriers in the pesticide field, however, this concept is very attractive for green pesticides, particularly in the reuse of insect sex attractant loaded nanofiber mats in traps

Additionally, with the development of melt electrospinning, new pesticide delivery systems based on bionic scaffolds have come into view The stent structure has the typical benefits of a drug delivery system, and the biocompatibility and protection offered by the bionic