PLA Chains Research Articles

Sealability and Seal Characteristics of PE/EVA and PLA/PCL Blends

Abstract Seal strength behavior of low density polyethylene and ethylene vinyl acetate copolymer (PE/EVA) blends as well as that of blends of a seal grade PLA with aliphatic polyester (PCL) was studied. Polyethylene is commonly used for seal application in packaging multilayer structures and amorphous PLA is considered to be its counterpart for compostable and/or biodegradables ones. Incorporation of EVA in polyethylene improves its sealability in terms of a decrease in seal initiation temperature and broadness of sealability plateau. This was interpreted as due to the formation of finer crystals, a decrease in the melting point and presence of vinyl acetate polar group. These were supported by results obtained from differential scanning calorimetry (DSC) and Scanning electron microscopy (SEM). For the PLA/PCL system, the dispersed phase was stretched into elongated ellipsoidal domains. This type of morphology affected the mechanical and seal properties of the blends. As a result of blending, both hot-tack initiation temperature and strength as well as seal initiation temperature were enhanced. The enhancement in these seal properties was significant when the concentration of the dispersed phase exceeded 20 wt% in the blend. Hot-tack strength of up to twice of pure PLA was achieved through blending. This was attributed to the lower glass transition temperature of PCL, resulting in enhanced mobility of PLA chains and also the high aspect ratio of the dispersed phase. The maximum obtained hot-tack strength (1 200 g/25 mm) at 40 % dispersed content compared advantageously to commercially available polyolefin based sealant resins. The seal and hot-tack initiation temperatures were shifted to lower temperatures by as much as 30 °C, which can allow faster and more energy efficient sealing process.

Structural evolution of poly(lactic acid)/poly(ethylene oxide)/unmodified clay upon ambient ageing

ABSTRACTPoly(lactic acid) (PLA) and poly(ethylene oxide) (PEO)/unmodified clay masterbatches are compounded together in order to investigate the ambient ageing of the resulting PLA/PEO/clay ternary blends. Binary blends are miscible up to 20 wt PEO% and in ternary counterparts, clay is intercalated at a nanometric scale, similarly to the clay dispersion state in masterbatches. PEO/clay interactions are strong, as confirmed by the lower plasticization of ternary blends. Furthermore, structural modifications occurring over time are evidenced for all blends through the observation of changes in thermal responses. Over the 220‐day observation period, lower plasticized samples undergo physical ageing only whereas blends close to the miscibility limit know a rapid PLA/PEO phase separation without physical ageing. For blends with intermediate PEO concentrations, both phenomena are observed with slower PLA chain mobility transition. Remarkably clay appears to affect both phenomena, ternary blends having limited physical ageing and slower PLA/PEO segregation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40426.

Synthesis and characterization of poly(ester amide) from remewable resources through melt polycondensation

Biodegradable poly(ester amide)s (PEAs) were synthesized from lactic acid and 11-aminoundecanoic acid via melt polycondensation. Molecular weights, chemical structures and thermal properties of the poly(ester amide)s were char- acterized in terms of gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), 1 H nuclear magnetic resonance ( 1 H NMR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), respec- tively. The PEAs have low molecular weights and display a lower cold crystallization temperature as well as smaller crys- tallinity by comparison with the pure poly(lactic acid) (PLA). The incorporation of the 11-aminoundecanoic acid into the PLA chain not only improved the thermal stability but changed the decomposition process.

Strong enhancements of nucleation and spherulitic growth rates through amplified interfacial effects for immiscible linear polymer/comb-like copolymer double-layer films

Cellulose-graft-poly[poly(ethylene glycol) methyl ether acrylate] (Cell-g-PPEGA) and poly[poly(ethylene glycol) methyl ether acrylate] (PPEGA) comb-like copolymers were synthesized by electron transfer atom transfer radical polymerization (ARGET ATRP). PPEGA/PLA and Cell-g-PPEGA/PLA pairs are both immiscible as indicated by slightly decreasing glass transition temperatures of PLA in the blends measured by differential scanning calorimetry (DSC) and phase separation morphologies observed by a phase contrast optical microscope (PCOM). Cell-g-PPEGA/PLA and PPEGA/PLA double-layer films and neat PLA film were prepared to measure the nucleation and spherulitic growth rates during isothermal crystallization at various temperatures above the melting points of Cell-g-PPEGA and PPEGA layers by using a polarized optical microscope (POM). In contrast to our previous results on the miscible polymer pairs, covering the immiscible molten PPEGA layer can greatly accelerate the spherulitic growth rates for PLA and the Cell-g-PPEGA layer shows a similar but less significant effect. Nevertheless, nucleation density is much higher for the Cell-g-PPEGA/PLA film than for the PPEGA/PLA and neat PLA films. A significant finding is that although the whole double-layer film systems represent phase separated ones, the densely grafted PEGA chains in the comb-like copolymers can simultaneously take action to amplify the segmental mobility of PLA chains through local contacts at interfacial layers between phase separated domains, which significantly enhances the formation of chain folding lamellae of the PLA, resulting in obvious enhancements of the crystallization kinetics.

New [ONOO]-Type Amine Bis(phenolate) Ytterbium(II) and -(III) Complexes: Synthesis, Structure, and Catalysis for Highly Heteroselective Polymerization of rac-Lactide

Two divalent ytterbium (Yb(II)) complexes, 1 and 2, supported by new [ONOO]-type amine bis(phenolate) ligands L(a,b) were synthesized in good yield by an amine elimination reaction of Yb(II)(N(SiMe3)2)2(TMEDA) (TMEDA = tetramethylethylenediamine) with one equivalent of the ligand precursor. X-ray structural determination showed complexes 1 and 2 both have a monomeric structure. Each adopts distorted octahedral coordination geometry around the six-coordinate Yb(II) ion. Two new trivalent ytterbium (Yb(III)) aryloxide complexes, 4 and 5, bearing [ONOO]-type amine bis(phenolate) ligands L(c) and L(d) were prepared by double-protonation reaction of Yb(C5H5)3THF with one equivalent of the ligand precursor, then one equivalent of phenol. Complex 4 has a symmetric dimeric structure with a Yb2O2 core bridging through the oxygen atoms of the OC6H4-4-CH3 groups. Complex 5 is a THF-solvated monomer. Each six-coordinated Yb(III) ion in both complexes adopts a distorted octahedron. All the complexes synthesized together with the known Yb(II) complex 3 were evaluated in the ring-opening polymerization (ROP) of rac-lactide (rac-LA). Complexes 1 and 4 were found to be extremely active for controlled ROP of rac-LA, as judged by narrow molar mass distributions (Mw/Mn: 1.07-1.16 for complex 1 and 1.07-1.10 for complex 4) and experimental molar mass Mn,exp values in good agreement with theoretic Mn,calcd values calculated on a single PLA chain produced per metal center of initiator. Complex 5 is less controlled. Complexes 1, 4, and 5 exhibited the same high stereoselectivity to give heterotactic polylactide with a Pr (probability of racemic enchainment of monomer units) ranging from 0.97 to 0.99. Dramatic decreases in activity and stereoselectivity were found for complexes 2 (Pr = 0.82) and 3 (Pr = 0.67), indicating the framework of L in the unit of [YbL] is crucial for determining activity and stereoselectivity of either Yb(II) or Yb(III) complexes.

Inhibition Mechanism of P-glycoprotein Mediated Efflux by mPEG-PLA and Influence of PLA Chain Length on P-glycoprotein Inhibition Activity

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

Preparation and Characterization of Poly(lactic acid) with Different Molecular Weights by Thermal Hydrolysis

A feasible and effective method of thermal hydrolysis to prepare poly (lactic acid) (PLA) oligomers with different controlled molecular weight from PLA is presented in this paper. The thermal hydrolytic reaction was carried out by immerging PLA resin pellets in boiling distilled water for a certain period of time. Ester groups in PLA chains are hydrolytically degraded in the presence of water and thermal, so PLA oligomers with different molecular weight were prepared. The structures and properties of PLA oligomers were characterized by FT-IR, GPC, DSC, etc. The results showed that thermal hydrolytic reaction could effectively reduce the molecular weight of PLA, which declines with the increase of the thermal hydrolytic reaction time. Meanwhile, the content of terminal hydroxyl group, glass transition temperature, melting point of PLA oligomers prepared from thermal hydrolytic reactions exhibit gradual changes with the extension of the thermal hydrolytic time.

Ring-Opening Polymerization of l-Lactic Acid O-Carboxyanhydrides Initiated by Alkoxy Rare Earth Compounds

The ring-opening polymerization of l-lactic acid O-carboxyanhydrides was initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high yields and relatively high molecular weight PLAs were obtained within 4 h at 25 °C. The reaction was highly controllable and easy to conduct, and the molecular weight distribution of the PLAs was rather narrow (Mw/Mn = 1.10–1.36). NMR analysis showed that one end of the PLA chain consisted of an isopropoxy group, while the other end of the chain contained a hydroxyl group. Due to their availability and high polymerizability, Lac-OCAs are promising monomers for the preparation of tailored architectures derived from well-defined PLAs.

Influence of chain structure on crystal polymorphism of poly(lactic acid). Part 1: effect of optical purity of the monomer

The influence of chain structure on crystal polymorphism of poly(lactic acid) (PLA) with high l-lactic acid content (97.8–100 %) is detailed in this contribution. Upon usual processing conditions of PLA, only α and α′ crystals grow, which makes these two polymorphs of major interest for research. The two crystal modifications have similar chain packing, which complicates their quantitative analysis by diffraction methods. The two crystal modifications are instead easily identified by analysis of the crystallization kinetics, which varies not only with temperature, but also with crystal polymorphism. The dependence of the rate of ordering on temperature shows two distinct maxima around 105–110 and 120–125 °C, which are related to growth of α′ and α crystals, respectively. Addition of d-lactic acid co-units leads to a decrease of the overall crystallization rate of PLA, as well as of the rate of spherulite growth (G) of both the crystal modifications. The relative crystallization rates of α and α′ forms are highly affected by stereoregularity, especially in the PLA grades that have a high crystallization rate. A high d-lactic acid content results not only in an overall slower crystal growth, but also in a varied temperature range where each of the two crystal modifications prevail, with a shift to lower temperatures of both the maxima of the G vs. temperature plots, indicating that inclusion of d-lactic acid units in the PLA chain affects crystallization rate of both α and α′ crystal modifications.

Role of surface chemical groups on carbon nanotubes in nucleation for polymer crystallization: Interfacial interaction and steric effect

Effects of surface functionalization of carbon nanotubes (CNTs) on their nucleation ability for poly(l-lactide acid) during isothermal and nonisothermal crystallization were investigated. The results showed that the surface functional groups reduced the nucleation ability of CNTs. The polarity of the functional CNTs was notably changed due to the presence of covalent groups (i.e., –OH, –COOH, and –F), giving rise to varied interactions with PLA chains. Three types of CNTs possessed different nucleation ability, depending on interfacial interaction and steric effect. Thereinto, by virtue of the superior polarity of –COOH group, the nucleation efficiency of CNTs-COOH surpassed that of CNTs-OH and CNTs-F despite the larger bulk of –COOH group, which might impede the movement of polymer chains towards the CNT surface. The steric hindrance of –F group was weaker than that of –OH group while the interfacial interaction was opposite, thus CNTs-OH and CNTs-F showed a commensurate effect on accelerating PLA crystallization. On the basis of surface-induced conformational ordering, a necessary approach for CNT-induced polymer crystallization was suggested that the functional groups played a counteraction or competition on nucleation efficiency of functional CNTs attributing to the interfacial interaction and the steric effect.

Evaluating Poly(lactic acid) Fiber Reinforcement with Modified Tannins

PLA fibers with high tannin content are prepared by melt spinning PLA with tannin acetate (TanAc) prepared from a condensed tannin. PLA with up to 50% TanAc content can be readily processed, giving melt spun fibers suitable for further processing as textile fibers or for carbonization. The PLA molecular weight profile is not impacted by blending with TanAc. Melt processing does not de-esterify the TanAc nor lead to transesterification between tannin and PLA chains in the presence of a tin catalyst. PLA polymer properties and NMR relaxation parameters suggest higher TanAc content gives greater change to PLA molecular mobility and reduced crystallinity, particularly in the presence of the transesterification catalyst.

Novel nanomicelles originating from hydroxyethyl starch-g-polylactide and their release behavior of docetaxel modulated by the PLA chain length

A novel drug carrier was synthesized through grafting polymerization of hydroxyethyl starch (HES) and d,l-lactide. By changing the molar ratio of HES and d,l-lactide, HES-g-PLA copolymers with different chain lengths of PLA can be obtained. Their chemical structures were characterized by FT-IR and 1H NMR. Through self-emulsification combined with solvent evaporation, HES-g-PLAs self-assembled into micelles with uniform sizes ranging from 65 to 130nm, depending upon the chain length of PLA. In vitro release profiles of docetaxel-loaded HES-g-PLAs meet first-order release kinetics via a mechanism of diffusion and polymer chain relaxation. The size of the micelles and the amount of drug loading can be controlled by varying the chain length of PLA. Another significant result is that release rates of docetaxel can be also modulated by changing the chain lengths of the PLA segments.

Redox-Responsive Block Copolymers: Poly(vinylferrocene)-b-poly(lactide) Diblock and Miktoarm Star Polymers and Their Behavior in Solution

The synthesis of diblock and miktoarm star polymers containing poly(vinylferrocene) (PVFc) and poly(l-lactide) (PLA) blocks is introduced. End functionalization of PVFc was carried out via end capping of living carbanionic PVFc chains with benzyl glycidyl ether (BGE). By hydrogenolysis of the benzyl protecting group a dihydroxyl end-functionalized PVFc was obtained. Both monohydroxyl- and dihydroxyl-functionalized PVFcs have been utilized as macroinitiators for the subsequent polymerization of l-lactide via catalytic ring-opening polymerization. A series of block copolymers and AB2 miktoarm star polymers was synthesized with varied PLA chain lengths. All polymers were characterized in detail, using 1H NMR spectroscopy, size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF). The molecular weight of the block copolymers and AB2 miktoarm star polymers are in the range of 8000–15000, containing a PVFc block of weight 7800. In addition, the self-assembly behavior of the polymers in dichloromethane (CH2Cl2) was investigated by using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In a selective solvent for PLA the block copolymers and miktoarm star polymers formed vesicle-like structures with different diameters.

Relationship between the rigid amorphous phase and mesophase in electrospun fibers

We investigated the molecular orientation, crystallization mechanism, phase structure and transitions of aligned electrospun fibers, including the constrained amorphous phase and its relationship to the mesophase. Aligned poly(lactic acid) (PLA) fibers were successfully electrospun (ES) by adopting a high-speed rotating wheel as the counter electrode. Using thermal analysis and wide angle X-ray scattering (WAXS), we evaluated the confinement that exists in as-spun amorphous, and heat-treated semicrystalline, fibers. Differential scanning calorimetry confirmed the existence of a constrained amorphous phase in as-spun aligned fibers, without the presence of crystals or fillers to serve as fixed physical constraints. Then, using WAXS, for the first time the mesophase fraction, consisting of oriented non-crystalline PLA chains, was quantitatively characterized in PLA nanofibers. The formation of oriented crystals during subsequent heating, and the evolution of the phase fractions (crystal, mobile amorphous, and constrained amorphous) with temperature, were investigated as to their dependence upon the method of fixing the ends of the fibers. In free-end ES nanofibers, the mesophase does not directly transition into the crystal phase of higher packing order. Instead, at temperatures above Tg, the free-end fiber undergoes residual stress relaxation, accompanied by the devitrification of the mesophase from a confined solid state to a mobile liquid state. The mesophase, which possesses some degree of medium-range order, behaves very similarly to the rigid amorphous phase, and a correlation between the two is established in free-end fibers. On the other hand, for fixed-end as-spun fibers, the mesophase forms a more ordered structure when heated. By fixing the fiber ends, relaxation of the mesophase above Tg is partially disabled. The more ordered mesophase that survives above Tg undergoes a mesophase-to-crystal phase transition upon further heating, making an additional contribution to the heat of fusion. A new phase structure model is proposed to describe aligned electrospun PLA nanofibers.

Poly(lactic acid)/natural rubber/cellulose nanocrystal bionanocomposites Part I. Processing and morphology

PLA/NR/cellulose nanowhisker composites were prepared using three types of cellulose nanocrystals (CNC), i.e. unmodified CNC obtained from acid hydrolysis of microcrystalline cellulose and two surface modified CNC. The two modification reactions, consisting on the grafting of long alkyl chains and of PLA chains onto the cellulose nanocrystals were carried out in order to facilitate the incorporation of the nanocrystals in the PLA/NR blend. A novel processing method was optimized combining solvent casting and extrusion in order to obtain a homogeneous dispersion of the nanofillers in the blend. The CNC modifications determined their location in the PLA/NR blend and influenced its morphology.

Parameters characterizing the kinetics of the nonisothermal crystallization of thermoplastic starch/poly(lactic acid) composites as determined by differential scanning calorimetry

AbstractTo guide the use of thermoplastic starch (TPS)/poly(lactic acid) (PLA) composites, the nonisothermal crystallization kinetics of pure PLA and TPS/PLA composites were investigated with differential scanning calorimetry (DSC) at three different cooling rates. The results indicate that the TPS/PLA composites showed different crystallizations because of their different contents and different cooling rates. TPS, as a nucleating agent, improved the crystallinity of the PLA and constrained the mobility of the PLA chains. Three theoretical models, namely, the Avrami, Ozawa, and Mo models, were used to describe the process of nonisothermal crystallization. The Avrami analysis modified by Jeziorny and the Mo method was successful in describing the nonisothermal crystallization process of the pure PLA and the TPS/PLA composites. However, the Ozawa analysis could not give an adequate description. Kinetic parameters such as the Avrami exponent, kinetic crystallization rate constant, relative degree of crystallinity, and crystallization enthalpy, among others, were determined at various scanning rates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

The preparation of multi-walled carbon nanotube/poly(lactic acid) composites with excellent conductivity

Multi-walled carbon nanotube (MWCNT)/poly(lactic acid) (PLA) composites were prepared by meltblending and hot-press processing. First, stearyl alcohol was added to the acid-treated MWCNTs (MWCNT-COOH); it reacted with the carboxylic group to form modified MWCNT with long alkyl chain of 18 carbons (MWCNT-C18). Furthermore, the MWCNT-C18 and PLA were then mixed and a small amount of transesterification agent (TA) was added, so that the MWCNT-C18 was grafted onto PLA chains by transesterification. The results show that an excellent dispersion of modified MWCNT in the PLA matrices was achieved. Moreover, two Tms and re-crystallization peak are found for the TA-modified MWCNT/PLA composites, but they do not appear for the non-TA-modified ones. SEM analysis shows that an excellent dispersion of modified MWCNT in the PLA matrices was achieved. Composites with the addition of 3wt.% MWCNT-C18 and 3wt.% TA-modified MWCNTs showed increases in the storage modulus at 40°C of 77.4% and 88.0%, respectively. The increases of loss modulus at the glass transition temperature were 43.8% and 75.6%, respectively. The surface resistivity of the PLA decreased from 5.30×1012 to 8.58×10−2Ω/sq after the addition of 3wt.% TA-modified MWCNTs.

Preparation of stealth micellar nanoparticles of novel biodegradable and biocompatible brush copolymers with cholesteryl-modified PLA and PEG side chains

Novel amphiphilic brush copolymers, P(CPLAMA)-co-P(PEGMA), of cholesteryl poly(l-lactic acid) (CPLA) and poly(ethylene glycol) monomethyl ether (PEG) with determined hydrophobic/hydrophilic ratios were synthesized by the methacrylate (MA) macromonomer copolymerization method. Brush copolymers were prepared via both free radical polymerization (FRP) and atom transfer radical polymerization (ATRP). The copolymer compositions were determined by 1H NMR spectroscopy. The synthesized copolymers were used to prepare the micellar nanoparticles with hydrophobic CPLA and hydrophilic PEG forming the core and shell, respectively. The critical micelle concentration (CMC) values of the samples produced by FRP (brush copolymer 1) and ATRP (brush copolymer 2) were estimated to be approximately 0.9 and 0.7 mg/L in aqueous solution by a fluorescence probe technique, respectively. The transmission electron microscopy (TEM) images of micelles of the brush copolymers 1 and 2 showed that micelles were spherical in shape with a mean diameter of 111 and 32 nm, respectively. The results showed that the size of micelles became larger with the increase of the molecular weight of polymer and the relative content of the hydrophilic PEG as well. The drug loading efficiency and drug-releasing properties of the micelles were investigated by using naproxen as a hydrophobic model drug. The in vitro release of naproxen-loaded micelles with about 85–89 % loading efficiency and 17–18 % loading capacity was studied by a using dialysis method in phosphate-buffered solution at 37 °C. The drug-releasing characteristics exhibited a phase of slow release. On the basis of the results obtained, the proposed brush copolymers may be useful in various targeted drug delivery applications, especially those involving hydrophobic drugs.

Properties of electrospun pollock gelatin/poly(vinyl alcohol) and pollock gelatin/poly(lactic acid) fibers

Pollock gelatin/poly(vinyl alcohol) (PVA) fibers were electrospun using deionized water as the solvent and pollock gelatin/poly(lactic acid) (PLA) fibers were electrospun using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the solvent. The chemical, thermal, and thermal stability properties were examined for the electrospun samples. The electrospun PVA samples generally had thinner and more uniform fibers than the electrospun PLA samples. For the PVA samples, an increase in total solids content and PVA to gelatin ratio generally resulted in higher average fiber diameter values and wider diameter distributions. Pollock gelatin in both types of electrospun samples remained amorphous. The PVA in electrospun samples had comparable melting temperatures to that of neat PVA, whereas the PLA in electrospun samples had slightly lower melting temperatures than that of neat PLA. Also, the PLA in electrospun samples had crystallization temperatures approximately 30°C lower than that in neat PLA. This was due to better alignment of PLA chains during electrospinning, which resulted in the chains being more readily crystallized at lower temperatures. In addition, the electrospun PVA samples completely dissolved in water at room temperature after soaking for one day, whereas the electrospun PLA samples remained intact even after soaking for three days.

Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B

BackgroundThe purpose of this study was to develop a self-aggregated nanoparticulate vehicle using an amphiphilic poly(lactic acid)-grafted-chitosan (PLA-g-CS) copolymer and to evaluate its potential for ocular delivery of amphotericin B.MethodsA PLA-g-CS copolymer was synthesized via a “protection-graft-deprotection” procedure and its structure was confirmed by Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra. Amphotericin B-loaded nanoparticles based on PLA-g-CS (AmB/PLA-g-CS) were prepared by the dialysis method and characterized for particle size, zeta potential, and encapsulation efficiency. Studies of these AmB/PLA-g-CS nanoparticles, including their mucoadhesive strength, drug release properties, antifungal activity, ocular irritation, ocular pharmacokinetics, and corneal penetration were performed in vitro and in vivo.ResultsFourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra showed that the PLA chains were successfully grafted onto chitosan molecules and that crystallization of chitosan was suppressed. The self-aggregated PLA-g-CS nanoparticles had a core-shell structure with an average particle size of approximately 200 nm and zeta potentials higher than 30 mV. Amphotericin B was incorporated into the hydrophobic core of the nanoparticles with high encapsulation efficiency. Sustained drug release from the nanoparticles was observed in vitro. The ocular irritation study showed no sign of irritation after instillation of the PLA-g-CS nanoparticles into rabbit eyes. The minimal inhibitory concentration of the AmB/PLA-g-CS nanoparticles showed antifungal activity similar to that of free amphotericin B against Candida albicans. The in vivo ocular pharmacokinetic study suggested that the PLA-g-CS nanoparticles have the advantage of prolonging residence time at the ocular surface. The corneal penetration study showed that the PLA-g-CS nanoparticles could penetrate into the cornea.ConclusionOur results suggest that this nanoparticulate vehicle based on a PLA-g-CS copolymer might be a promising system for effective ocular delivery of amphotericin B.