Preparation and characterization of crosslinked chitosan microspheres for the colonic delivery of 5-fluorouracil

In this work, we attempted to develop a simple and inexpensive colon specific pulsatile drug-delivery system using chitosan microspheres loaded with 5-fluorouracil (5-FU) using an enteric-coated soft gelatin capsule. Chemical crosslinking by glutaraldehyde and interactions between the polymer and the drug were determined by Fourier transform infrared spectral study. Scanning electron microscopy of the microspheres revealed spherical shapes with smooth surfaces. Differential scanning calorimetry studies confirmed the molecular dispersion of the drug in the polymer matrix. Three different formulations (i.e., F1, F2, and F3) were prepared by the variation of the amount of 5-FU. Encapsulation efficiencies of 5.5, 10.8, and 17.9% for drug loadings of 10, 20, and 50%, respectively, were obtained. In vitro release studies were conducted at pH 1.2 and pH 7.4 (to simulate actual gastrointestinal fluid and gastrointestinal tract conditions, respectively). The results indicate that chitosan microspheres released 5-FU in both acidic (60%) and basic pH (40%) conditions, whereas the capsule (filled with chitosan microspheres) showed only 8–10% release in acidic media and nearly 90% in basic media within 12 h. The newly designed pulsatile capsule device could be used for targeting 5-FU to the colon. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Novel blend microspheres of poly(vinyl alcohol) and succinyl chitosan for controlled release of nifedipine

Water-soluble succinyl chitosan (SCS) was synthesized by reacting succinic anhydride with –OH and –NH₂ reactive groups of chitosan (CS). The blend hydrogel microspheres were prepared from SCS with poly(vinyl alcohol) (PVA) by water-in-oil (w/o) emulsion cross-linking using glutaraldehyde (GA) as the cross-linking agent. Nifedipine (NFD), an antihypertensive drug having a plasma half-life of 2 h, was encapsulated giving encapsulation efficiency up to 92 % and its release was extended up to 12 h. Scanning electron microscopy (SEM) confirmed the spherical nature and smooth surfaces of the microspheres, while Fourier transform infrared spectroscopy (FTIR) confirmed succinylation of CS and chemical stability of NFD in the matrix. Thermogravimetry (TGA) and differential scanning calorimetry (DSC) characterized the SCS and the blend hydrogel microspheres. X-ray diffraction (XRD) and DSC were also used to study the crystalline or amorphous nature of NFD. Swelling and in vitro release experiments performed in pH 1.2 and 7.4 buffer media showed a dependence of blend composition, extent of cross-linking and pH of the media. The mechanism of drug release as analyzed by an empirical equation, suggested non-Fickian trends.     

APPLICATION OF A DISSOLUTION-DIFFUSION MODEL TO THE RELEASE OF 5-FLUOROURACIL FROM POLYMER MICROSPHERES

A theoretical discussion of drug release from microspheres is provided and a model-based predictive algorithm developed. The model verification step includes literature data describing the release profile of 5-fluorouracil (5-FU) from poly(lactic acid) polymer. Material balance equations were written to describe drug transport from a porous sphere. The model included combined effects of dissolution, diffusion, and void fraction on the release of 5-FU and was validated against in vitro experimental data. Analyses, conducted on published 5-FU release test data, revealed that the process was governed by a dissolution-diffusion mechanism. Approximately 1.5 million microspheres were formed; the drug density, diffusivity, and dissolution rate constant were estimated at 1.110 g/cm³, 2.324 × 10^?15 m²/s, and 17.60 g/m³h, respectively. The dissolution rate was faster than the rate of diffusion by a ratio of 12.79 to 1. Manipulation of the microsphere porosity was an effective way to influence the diffusion-controlled process. The procedure, outlined in the study, for estimating process properties will help fabricate microspheres that meet specific requirements.     

Biodegradable polymeric microspheres of gelatin and carboxymethyl guar gum for controlled release of theophylline

Carboxymethyl guar gum (CMGG) was synthesized by carboxymethylation of guar gum (GG), which was blended with gelatin (GE) to obtain a novel semi-interpenetrating polymer network (semi-IPN) in the form of microspheres prepared by water-in-oil emulsion method to investigate the controlled release of theophylline (THP), an antiasthmatic drug. Electronic spectroscopy revealed the drug encapsulation ranging from 56 to 74 %. Fourier Transform infrared spectroscopy confirmed the carboxymethylation of GG as well as the semi-IPN structure of the blend polymer. Scanning electron microscopy indicated the smooth surfaces with spherical microspheres. Differential scanning calorimetric and X-ray diffraction studies showed the molecular level dispersion of drug in the microspheres. The in vitro drug release profiles were analyzed to study the effect of polymer blend composition, % drug loading and amount of glutaraldehyde added as a crosslinker. The drug release was extended up to 26 h. The in vitro release data performed in acidic and alkaline media were analyzed using the empirical equations to understand the release profiles of THP.     

Preparation and Characterization of Carboxymethyl Chitosan and β-Cyclodextrin Microspheres by Spray Drying

Three kinds of carboxymethyl chitosan/β-cyclodextrin microspheres loaded with theophylline were prepared by spray drying intended for pulmonary delivery. Mucociliotoxicity, permeation rate, and drug release characteristics of the product were investigated. The microspheres obtained by spray drying were found to be spherical with smooth or wrinkled surfaces. The mean particle size was between 3.39 and 6.06 µm. The microspheres demonstrated high product yield (43.7–50.2%), high drug loading (13.7–38.1%), and high encapsulation efficiency (86.9–92.8%). FT-IR indicated that there were interactions of theophylline with carboxymethyl chitosan matrix. Further studies on mucociliotoxicity and permeation confirmed that microspheres had better adaptability and high permeation rate. In vitro drug release from the microspheres was not related to the drug/polymer ratios.     

In vitro release study of diltiazem hydrochloride from poly(vinyl pyrrolidone)/sodium alginate blend microspheres

Polymeric blend microspheres of poly(vinyl pyrrolidone) (PVP) with sodium alginate (NaAlg) were prepared by cross‐linking with calcium ions and used to deliver a calcium channel blocker drug, diltiazem hydrochloride (DT). The prepared microspheres were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Scanning electron microscopy confirmed the spherical nature of the particles. Preparation conditions for the microspheres were optimized by considering the percentage entrapment efficiency, particle size, and swelling capacity. Effects of variables such as PVP/NaAlg ratio, molecular weight of PVP, cross‐linker concentration, and drug/polymer ratio on the release of DT were discussed at two different pH values (1.2, 6.8) at 37°C. It was observed that DT release from the microspheres decreased with increasing molecular weight of PVP and extent of cross‐linking. However, DT release increased with increasing PVP content and drug/polymer ratio (d/p) of the blend microspheres. The highest DT release percentage was obtained as 99% for PVP/NaAlg ratio of 1/2 with d/p ratio of 1/2 at the end of 4 h. It was also observed from release results that DT delivery from the microspheres through the external medium are much higher at low pH (1.2) value than that of high pH (6.8) value. The drug release from the microspheres mostly followed Fickian transport. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation and characterization of pH sensitive poly(vinyl alcohol)/sodium carboxymethyl cellulose IPN microspheres for in vitro release studies of an anti-cancer drug

Interpenetrating polymeric network microspheres (IPNMs) consisting of poly(vinyl alcohol) and sodium carboxymethylcellulose were prepared by water-in-oil emulsion method and were cross-linked with glutaraldehyde. 5-Fluorouracil (5-FU), an anti-cancer drug, was loaded into IPNMs via in situ method. These IPNMs have been characterized by Fourier transform infrared spectroscopy, which confirms the cross-linking of IPNMs through glutaraldehyde. Differential scanning calorimetry and X-ray diffraction analysis of the drug-loaded IPNMs have confirmed uniform molecular dispersion of 5-FU in the IPNMs. Particle size measured using optical microscopy gave an average size of 80–250 μm. Scanning electron microscopy also confirmed the formation of microspheres with smooth surface and spherical shape. Encapsulation efficiency of 5-FU in these IPNMs was achieved up to 62%. Drug release profiles of the IPNMs at different pH conditions (pH 1.2 and 7.4) confirmed that microspheres formed are pH sensitive, resulting controlled release of drug during in vitro dissolution experiments. It has been analyzed with an empirical equation to understand the diffusion nature of drug through the IPNMs. Both encapsulation efficiency and release patterns are found to depend on the nature of the cross-linking agent as well as amount of drug loading. In vitro release studies indicated the release of 5-FU for more than 10 h.     

Graphene oxide/poly(<Emphasis Type="Italic">N</Emphasis>-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent

In this work, graphene oxide (GO)-incorporated composite beads were developed from poly(N-isopropyl acrylamide)/sodium alginate (PNIPAM/NaAlg) using ionotropic gelation technique. The interaction between GO and PNIPAM/NaAlg with Ca²⁺ ions as a cross-linker was investigated by Fourier transform spectroscopy. X-Ray diffraction pattern showed that the GO was distributed uniformly in the PNIPAM/NaAlg with Ca²⁺ ions while scanning electron micrograph technique revealed that composite beads were formed in spherical shape. The controlled release characteristics of composite beads were studied using 5-fluorouracil (5-FU) as anti-cancer model drug. The encapsulation efficiencies were found to be between 90 and 92% in all formulations. Furthermore, the equilibrium swelling ratio (%) and in vitro release studies of the beads were carried out in two different pH values of 1.2 and 7.4 and at different temperature conditions of 25 and 37 °C. The obtained results showed that the swelling ratio decreased with an increase in GO concentration. In vitro release studies performed in response to both pH and temperature and they proved that the 5-FU drug was released from composite beads over 32 h without burst release. Cytotoxicity results showed pristine composite beads are good cytocompatible. In addition, the cytotoxicity of 5-FU was found to be improved when incorporated with composite beads than pure 5-FU. It is therefore concluded that the developed composite beads have dual response and can be used as controlling released carriers in cancer drug delivery applications.     

Formulation of salicylate-based poly(anhydride-ester) microspheres for short- and long-term salicylic acid delivery

The formulation of salicylate-based poly(anhydride-ester) (PAE) microspheres was optimized by altering polymer concentration and homogenization speed to improve the overall morphology. The microspheres were prepared using three salicylate-based PAEs with different chemical compositions comprised of either a heteroatomic, linear aliphatic, or branched aliphatic moiety. These PAEs broadened the range of complete salicylic acid release to now include days, weeks, and months. The molecular weight (M _w ), polydispersity index (PDI) and glass transition temperature (T _g) of the formulated polymers were compared to the unformulated polymers. In general, the M _w and PDI exhibited decreased and increased values, respectively, after formulation, whereas the T _g changes did not follow a specific trend. Microsphere size and morphology were determined using scanning electron microscopy. These microspheres exhibited smooth surfaces, no aggregation, and size distributions ranging from 2 to 34 μm in diameter. In vitro release studies of the chemically incorporated salicylic acid displayed widely tunable release profiles.     

Development of tunable biodegradable polyhydroxyalkanoates microspheres for controlled delivery of tetracycline for treating periodontal disease

This article was aimed at preparation and characterization of drug delivery carriers made from biodegradable polyhydroxyalkanoates (PHAs) for slow release of tetracycline (TC) for periodontal treatment. Four PHA variants; polyhydroxybutyrate (PHB), poly(hydroxybutyrate‐co‐hydroxyvalerate) with 5, 12, and 50% hydroxyvalerate were used to formulate TC‐loaded PHA microspheres by double emulsion‐solvent evaporation method. We also compared the effect of different molecular weight (M_w) of polyvinyl alcohol (PVA) acting as surface stabilizer on particle size, drug loading, encapsulation efficiency, and drug release profile. The TC‐loaded PHA microspheres exhibited microscale and nanoscale spherical morphology under scanning electron microscopy. Among formulations, TC‐loaded PHB:low M_w PVA demonstrated the highest TC loading with slow release behavior. Our results showed that the release rate from PHA microspheres was influenced by both the type of PHA and M_w of PVA stabilizer. Lastly, TC‐loaded PHB microspheres showed efficient killing activity against periodontitis‐causing bacteria, suggesting its potential application for treating periodontal disease. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44128.     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Cumulative release of cefotaxim from interpenetrating networks of poly(vinyl alcohol-g-acrylamide) and chitosan-g-polyacrylamide chains

In this study, novel interpenetrating networks comprising of poly(vinyl alcohol-g-acrylamide) and chitosan-g-polyacrylamide chains were designed by redox polymerization method and their potential for controlled release of an antibiotic drug cefotaxim, and antibacterial and cytotoxic behaviors were evaluated. The polymer matrix hydrogel was loaded with cefotaxim drug by allowing it to swell in the drug solution reservoirs of concentrations varying in the range 0.1–0.5 mg/mL. The polymer network was examined by FTIR, SEM and DSC techniques for structural, morphological and thermal characterization. The FTIR spectra clearly confirmed the presence of functional groups of constituent polymers; the SEM image suggested a mesh-type morphology with approximate mesh dimensions of 10 μm × 20 μm. The DSC studies revealed a fall in glass transition temperature (Tg) of both chitosan and poly(vinyl alcohol) to 50 and 70 °C, respectively, from their native values. The release studies were performed in PBS (pH 7.4) under in vitro conditions and the drug release kinetics was investigated. It was found that the amount of drug released increases from 5.4 to 8.4 mg when the drug loading increases from 5.0 to 16.0 %. It was also found that when the pH rises from 1.8 to 7.4, an increase in drug release was noticed, while a further increase in pH to 8.6 resulted in a fall in the amount of released drug. The polymer matrix also showed fair antibacterial properties against E. coli and no cytotoxicity for L-929 mouse fibroblast cells.     

Synthesis and characterization of modified chitosan microspheres: Effect of the grafting ratio on the controlled release of nifedipine through microspheres

The grafting of acrylamide onto a chitosan backbone was carried out at three acrylamide concentrations (polymer/monomer ratio = 1:1, 1:2, and 1:3). The synthesis of the grafted polymer was achieved by K₂S₂O₈‐induced free‐radical polymerization. Microspheres of polyacrylamide‐g‐chitosan crosslinked with glutaraldehyde were prepared to encapsulate nifedipine (NFD), a calcium channel blocker and an antihypertensive drug. The microspheres of polyacrylamide‐g‐chitosan were produced by a water‐in‐oil emulsion technique with three different concentrations of glutaraldehyde as the crosslinking agent. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to characterize the grafted copolymers, and the microspheres were prepared from them. FTIR and DSC were also used to analyze the extent of crosslinking. The microspheres were characterized by the particle size; the water transport into these microspheres, as well as the equilibrium water uptake, were studied. Scanning electron microscopy confirmed the spherical nature of the particles, which had a mean particle size of 450 μm. Individual particle dynamic swelling experiments suggested that with an increase in crosslinking, the transport became case II. The release of NFD depended on the crosslinking of the network and on the amount of drug loading. Calculating the drug diffusion coefficients with the initial time and later time approximation method further supported this. The drug release in all 27 formulations followed case II transport, and this suggested that the time dependence of the NFD release followed zero‐order kinetics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2940–2949, 2003     

Temperature-Sensitive Microspheres for Controlled Release of Enalprilmaleate

Poly(N′-isopropylacrylamide-co–methacryl amide) has been prepared by free-radical emulsion polymerization. The copolymer was transformed into thermoresponsive microspheres by chemical crosslinking with N′, N′ Methylenebis-acrylamide (NNMBA). Enalpril maleate (ENAM), an anti-hypertensive drug, was successfully loaded into these microspheres during in-situ polymerization. DSC and X-RD analysis of the drug-loaded and plain microspheres have confirmed partial dispersion of ENAM in the microspheres. SEM confirmed the spherical nature of the particles with a mean particle size of 100 µm. Drug release profiles of these microspheres exhibited a prolonged release of ENAM for more than 12 h.     

Preparation and characterization of chitosan-poly(acrylic acid) polymer magnetic microspheres

A modified method to prepare chitosan-poly(acrylic acid)(CS-PAA) polymer magnetic microspheres was reported in this paper. First, via self-assembly of positively charged CS and negatively charged Fe₃O₄ nanoparticles, magnetic CS cores with a large amount of Fe₃O₄ nanoparticles were successfully prepared. Subsequently, the AA monomers were polymerized on the magetic CS cores based on the reaction system of water-soluble polymer-monomer pairs. These polymer magnetic microspheres had a high Fe₃O₄ loading content, and showed unique pH-dependent behaviors on the size and zeta potential. From the magnetometer measurements data, the CS-PAA polymer magnetic microspheres also had superparamagnetic property as well as fast magnetic response. A continuous release of the entrapped ammonium glycyrrhizinate in such polymer magnetic microspheres occurred, which confirmed the potential applications of these microspheres for the targeted delivery of drugs.     

Preparation of sodium alginate/poly(vinyl alcohol) blend microspheres for controlled release applications

Sodium alginate (NaAlg)/poly (vinyl alcohol) (PVA) blend microspheres (MS) were prepared by water-in-oil (w/o) emulsion method. These polymer microspheres were crosslinked with glutaraldehyde and loaded with metformin hydrochloride (MHC). The microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis to confirm the molecular dispersion of the drug, thermal stability, morphological properties, and crystallinity of the polymer matrix before and after blending. SEM of the microspheres suggested the formation of microspheres in spherical structure. Drug release data were analyzed using an empirical equation to understand the nature of drug transport through polymeric matrices. The controlled release (CR) characteristics of the polymer matrices was investigated in pH 7.4 media and from the results it was obtained that the drug was released in controlled manner up to 10 h. The physico-chemical properties of the microspheres were studied by calculating drug entrapment efficiency and drug release kinetics. Percent of encapsulation efficiency (% EE) decreased with increase in crosslinking agent (GA) and PVA content in the microspheres. The optimum % EE (80%) was observed in case of MS containing 40% of PVA with 15% MHC. The release profiles indicate that the release of MHC decreases with increasing the PVA/NaAlg (w/w) and drug/polymer ratio. At the end of 10 h, the highest release of MHC was found to be 96% for MS containing PVA/NaAlg (40 : 60) and 15 wt % drug loaded. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Chitosan reinforced with modified CaCO<Subscript>3</Subscript> nanoparticles to enhance thermal,hydrophobicity properties and removal of cu(II) and cd(II) ions

The role of nanoparticles (NPs) in the enhancement of thermal, wettability and adsorption properties of chitosan (CS) was inspired by loading of CaCO₃ modified with diacid (DA) based on L- phenyl aniline (2–8 wt%) within the CS by ultrasound agitation. The diameter of CaCO₃-DA into the CS extended from 40 to 70 nm. A thermal test on the CS/CaCO₃-DA nanocomposite (NC) 2 wt% revealed that T ₅ (temperature with 5% weight loss) was increased up to 312 °C, which is twice the value of the pure polymer. The wettability property of the CS/CaCO₃-DA NCs was transformed from hydrophilicity to hydrophobicity as the CaCO₃-DA NPs concentration was increased. It is due to decrease of the accessibility of the CS polar groups to water. The CS/CaCO₃-DA NC 5 wt% was selected as the adsorbent for uptake of metal ions from the wastewater. It showed maximum adsorption capacity of 21.74 and 29.41 mg.g^?1 for Cu(II) and Cd(II), respectively. These are attributed to strong complexation reaction between the metal ions and functional groups in the obtained NC.     

Construction of pH-responsive drug delivery platform with calcium carbonate microspheres induced by chitosan gels

Construction of simple and convenient platforms for controlled delivery of anti-cancer drugs is of great importance for medical science and pharmaceutics. Here, chitosan (CS) gels were used to induce the growth of calcium carbonate (CaCO₃) microspheres, and the resulting CaCO₃ microspheres were well dispersed within the three-dimensional (3D) network framework of the CS gels. The synthesized CaCO₃/CS composites were then examined by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR) and X-ray diffractometry (XRD). Finally, the designed CaCO₃/CS composites were used for loading and controlled delivery of methotrexate (MTX), an anti-cancer drug. The encapsulation ratio of MTX calculated by UV–vis spectroscopy was approximately 78.8%. In addition, pH-responsive delivery of MTX from the CaCO₃/CS composites was successfully achieved due to the pH-sensitive property of CS, and the cumulative release of MTX could reach 93.3%, 86.6% and 77.6% at pH 8.5, 7.4 and 5.8, respectively.     

pH-responsive nanosized-micelles based on poly(monomethylitaconate)-co-poly(dimethylaminoethyl methacrylate) and cholesterol side chains effect on pH change-induced release of piroxicam

Novel double hydrophilic poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA) synthesized via free radical polymerization of corresponding monomers with defined molar ratios in the presence of K₂S₂O₈ as an initiator in an aqueous solution. The resulting copolymer was subsequently converted to a cholesterol conjugate (PMMICholC₆-co-PDMAEMA) by esterification reaction with 6-cholesteryl-1-hexanol (CholC₆). Two copolymers self-assembled into micelles by simply adjusting the solution pH at room temperature. The non-conjugated polymer had a sharp transition at pH 5. TEM and DLS studies showed that both micelles were spherical in shape with a mean diameter around 85 and 26 nm, respectively. Piroxicam (PX) as a hydrophobic model drug was encapsulated into micelles. The results indicated that PMMICholC₆-co-PDMAEMA micelles were able to load more amounts of drug than PMMI-co-PDMAEMA micelles which could be attributed to the strong hydrophobic interactions of cholesterol molecules in the core. In vitro release studies demonstrated that PX release from PMMI-co-PDMAEMA micelles was significantly fast at physiological pH compared with mildly acidic pH 4.5. However, at pH 4.5, PMMICholC₆-co-PDMAEMA micelles, with core-shell-corona structure, released loaded drug molecules faster than pH 7.4 which contained a relatively steady drug release profile. In summary, cholesterol-modified micelles could be introduced as stable and effective pH responsive nanocarriers to make a promising system for enhancing the efficacy of hydrophobic drugs in cancer cells for improved cancer therapy.     

Synthesis, characterization, and drug delivery research of an amphiphilic biodegradable star-shaped block copolymer

An amphiphilic biodegradable three-arm star-shaped diblock copolymer containing poly(ε-caprolactone) (PCL) and poly(N-vinylpyrrolidone) (PVP) (TEA(PCL-b-PVP)₃) has been successfully synthesized by the ring-opening polymerization of ε-caprolactone (ε-CL), RAFT polymerization of N-vinylpyrrolidone and a coupling reaction of PCL with carboxyl-terminated PVP (PVP-COOH). In aqueous media, the star-shaped copolymer self-assembled into spherical micelles with diameters of near 106 nm. The critical micelle concentration of TEA(PCL-b-PVP)₃ copolymer was determined to be 5.96 × 10^?3 mg/mL. Folic acid was then used as a model drug to incorporate into TEA(PCL-b-PVP)₃ micelles, the drug loading content and encapsulation efficiency is 16.36 and 49.08 %, respectively. In vitro release experiments of the drug-loaded micelles exhibited sustained release behavior and it was affected by the pH of release media. These results indicate that the copolymer may serve as a promising “intelligent” drug delivery alternative.