Jinfang Yuan

Preparation and characterization of thermo-responsive amphiphilic triblock copolymer and its self-assembled micelle for controlled drug release

An amphiphilic thermo-responsive ABA triblock copolymer, poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-poly(ethylene-glycol) methyl ether methacrlate)-b-poly(methyl methacrylate) (PMMA-b-P(NIPAM-co-PEGMEMA)-b-PMMA), was designed and synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, and subsequently characterized by FT-IR, (1)H NMR and GPC. The copolymer can disperse in water and self-assemble into nanoscaled micelles in a flower-like arrangement at room temperature; the hydrophobic PMMA tucks in the core while the hydrophilic and improved biocompatible P(NIPAM-co-PEGMEMA) forms a thermosensitive outer shell. The resulting micelles were investigated using fluorescence spectroscopy, dynamic light scattering technique (DLS) and transmission electron microscopy (TEM). The copolymer exhibited a lower critical solution temperature (LCST) of around 39 degrees C via optical transmittance measurements. Notably, there was no copolymer precipitation observed at the LCST, which was propitious to in vivo use of the micelle. The micelles loaded with folic acid as a model drug showed a desired thermo-responsive drug release behavior. It was found that the rate and amount (maximum percentage 85%) of the drug release was much higher above the LCST than that (maximum percentage 36%) below the LCST. These results indicate that the thermosensitive triblock copolymer possesses promising potential applications as a smart drug carrier in biomedical science.

Preparation and drug controlled-release of polyion complex micelles as drug delivery systems

Block copolymers, poly(N-vinylprrolidone)-block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA) and poly(N-vinylprrolidone)-block-poly(N,N-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA), were synthesized by reversible addition- fragmentation chain transfer (RAFT) polymerization. In aqueous media, this a pair of oppositely-charged diblock copolymers could self-assemble into stable and narrow distribution polyion complex micelles (PICMs). Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that the micelles to be spherically shaped with mean hydrodynamic diameter around 70nm. In addition, the PICMs display ability to response to external stimuli. All of theses features are quite feasible for utilizing it as a novel intelligent drug delivery system. In order to assess its application in biomedical area, release profiles of coenzyme A (Co A) from PICMs were studied under both simulated gastric and intestinal pH conditions. The release was much quicker in pH 7.4 buffer than in pH 2.0 solution. Based on these results, these PICMs could be a potential pH-sensitive carrier for colon-specific drug delivery system.

Preparation, characterization and drug release behavior of polyion complex micelles

Double-hydrophilic block copolymer composed of poly(N-vinylpyrrolidone) (PVP) and poly(styrene-alter-maleic anhydride) (PSMA) has been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Poly(N-vinylpyrrolidone)-block-poly(styrene-alter-maleic anhydride) (PVP-b-PSMA) thus formed was characterized by gel permeation chromatography (GPC), (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy and FTIR spectroscopy. In acid solution, this block copolymer spontaneously formed polyion complex (PIC) micelles with a cationic polyelectrolyte, chitosan. The PSMA/chitosan polyelectrolyte complex formed an inner core while PVP chains surrounded it as a shell. Transmission electron micrographs (TEMs) and dynamic light scattering (DLS) showed the PIC micelles to be spherically shaped, with mean hydrodynamic diameter around 146 nm. The model drug coenzyme A (CoA) was loaded into the micelles and the in vitro drug release behavior was investigated. We found that by manipulating the pH value and salt concentration of the release solution, it was possible to control the releasing rate of CoA.

Self-assembled Polyion Complex Micelles based on PVP-b-PAMPS and PVP-b-PDMAEMA for Drug Delivery

The double hydrophilic block copolymer, poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid), was synthesized by reversible addition-fragmentation chain transfer RAFT polymerization. Gel permeation chromatography, 1H-NMR, and FTIR were used to determine the structure and composition. In aqueous media, this block copolymer spontaneously forms polyion complex (PIC) micelles with an oppositely charged block copolymer, poly(N-vinylpyrrolidone)-block-poly(N, N-dimethylaminoethyl methacrylate). Dynamic light scattering and transmission electron micrograph showed that the micelles were <200 nm in diameter and had a narrow single distribution. The release profiles of folic acid, incorporated into the micelles, showed remarkable pH responsive behavior. The PIC micelles exhibited good biocompatibility based on MTT assay with human embryonic kidney (HEK293) cells. These PIC micelles have the potential as pH-sensitive carriers for drug delivery.

ABC triblock copolymers with pH-responsive LCST for controlled drug delivery

The thermo- and amphiphilic ABC triblock copolymers, single-methoxypoly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-acrylic acid)-b-poly(methyl methacrylate), were synthesized by reversible addition fragmentation chain transfer radical polymerization. The triblock copolymers were characterized by Fourier transform infrared spectroscopy, 1H-NMR, and gel permeation chromatography. The copolymers self-assemble into thermo-responsive nano-sized micelles in aqueous media. Transmission electron microscopy and dynamic light scattering showed that the micelles were regularly spherical in shape with an average diameter ~120 nm. Fluorescence analysis indicated that the triblock copolymer had a low critical micelle concentration of 2.5 mg/L in aqueous media at pH 7.4 and room temperature. The lower critical solution temperature (LCST) of the micelles could be altered by simply changing the pH. The LCST of the triblock copolymer at pH 5.5 was altered to 37.5 ° C (close to physiological temperature) by copolymerizing N-isopropylacrylamide with acrylic acid. When the pH was increased to 7.4, the LCST increased to 55°C and it decreased to 33°C when the pH was 2.0. The micelles exhibited good biocompatibility with human embryonic kidney cells, when the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed. The controlled release of folic acid (FA) from FA-loaded micelles under different conditions was evaluated. The rate and amount of the drug released were greater above the LCST than below it.

Synthesis and characterization of polyion complex micelles and their controlled release of folic acid.

Stable and narrow distribution polyion complex micelles (PICMs) were prepared in an aqueous milieu through electrostatic interaction between a pair of oppositely charged block copolymers poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PVP-b-PAMPS) and monomethoxy poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP). The critical aggregate concentration (CAC), hydrodynamic size, and surface morphology of the prepared PICMs were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), respectively. The resulting CAC and the average diameter of the PICMs were about 43 mg/L and 121 nm, indicating high structural stability of micelles and a size favorable for delivery of drug. In addition, the PICMs exhibited good biocompatibility using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293) cells. All of these features are quite feasible for utilizing the PICMs as a novel intelligent drug delivery system. In order to assess its application in the biomedical area, the model drug folic acid (FA) was loaded into the micelles and the in vitro drug release behavior was investigated. We found that by manipulating the pH value and salt concentration of the release solution, it was possible to control the release rate of FA.

Self-assembled polyion complex micelles for sustained release of hydrophilic drug

Graft copolymer polyethylenimine–graft–poly(N-vinylpyrrolidone) (PEI-g-PVP) was prepared by coupling mono carboxyl-terminated PVP (PVP–COOH) with PEI using N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) as coupling agents. In aqueous medium, PVP–g–PEI can self-assemble into stable polyion complex micelles with an oppositely charged block copolymer, poly(N-vinylpyrrolidone)–block–poly(2-acrylamido-2-methyl-1-propanesulphonic acid) (PVP-b-PAMPS). Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 142u2009nm. To estimate their feasibility as vehicles for drugs, the model drug folic acid (FA) was incorporated into the cores of the micelles via electrostatic interactions. In vitro release test of FA showed that the drug-release rates are dependent on the pH value of the release media. Based on these results, we can conclude that the polyion complex micelles prepared from the PEI-g-PVP/PVP-b-PAMPS copolymers have great potential as drug delivery nanocarriers.

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 106xa0nm. The critical micelle concentration of TEA(PCL-b-PVP)3 copolymer was determined to be 5.96xa0×xa010−3xa0mg/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 49.08xa0%, 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.

Preparation and release behavior of pH and ionic sensitive chitosan/poly(vinylpyrrolidone) semi-IPN beads for coenzyme A

Abstract A series of pH- and ionic sensitive semi-interpenetrating polymer network (semi-IPN) beads of chitosan (CS) and poly(vinyl pyrrolidone) (PVP) were prepared using glutaraldehyde as crosslinking agent and characterized for the release of coenzyme A (Co A). The swelling behavior of the semi-IPN beads and the influential factors, such as the component ratio of CS and PVP, the loaded amount of Co A, the pH and ionic strength of the release medium on Co A release were studied. The results showed that within 48 h the cumulative release rate of Co A decreased with Co A loading content, ionic strength increase or crosslinking time increase; when the weight ratios of CS to PVP in the drug-loaded beads were 100:0, 80:20, 60:40, 50:50, 40:60 and 20:80, the cumulative release rates of Co A at pH 2.1 solution were 95.2, 72.1, 73.2, 74.2, 86.5 and 80.1%, respectively, and they were 22.7, 30.1, 28.0, 33.1, 38.4 and 35.2% at pH 7.4 solution, respectively. All the results indicated that the CS/PVP semi-IPN beads were suitable for drug delivery systems.