Preparation and properties of a novel thermo-responsive poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) hydrogel containing glycyrrhetinic acid

A novel thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel containing glycyrrhetinic acid(GA) was synthesized by free radical copolymerization. The structure of the product was confirmed by FT-IR and ¹H-NMR spectra. The temperature responsibility and swelling properties of the copolymerized hydrogel were investigated by differential scanning calorimetry (DSC) and gravimetric methods. The results indicated that GA-incorporated hydrogel was still temperature responsive and the swelling ratio decreased with the increasing of temperature. The lower critical solution temperature (LCST) of GA-incorporated hydrogel and poly(N-isopropylacrylamide) hydrogel was 30.00 °C and 31.21 °C, respectively, in distilled water. However, these two values were shifted to 28.22 °C and 29.16 °C in cell culture media. The novel hydrogel also exhibited reversible temperature responsibility. Deswelling kinetics indicated that the copolymerized hydrogel deswelled more rapidly than poly(N-isopropylacrylamide) hydrogel. Since GA has specific binding capacity to asialoglycoprotein receptors on the membrane of hepatocyte, this novel hydrogel with GA could be expected as good candidate for hepatic cell culture.     

Characterisation of Biodegradable Microspheres Containing Dehydro-Iso-Androsterone

Abstract

Poly-DL-lactide (PLA) and poly-DL-lactide-co-glycolide (DL-PGA) micromatrices (PharmazomesTM) containing dehydro-isoandrosterone (DHEA), a weak androgen, were prepared by a solvent evaporation process. Micromatrices with increasing drug loading as well as increasing polymer molecular weight were prepared. The morphology of these systems depended on the drug loading, the polymer molecular weight and polymer composition. Increasing the drug loading or polymer molecular weight resulted in increasingly irregular microparticles being formed. DSC thermograms did not reveal the presence of crystalline DHEA in micromatrices containing 10 to 50% DHEA loading. However crystalline DHEA was observed in microspheres heated to above the glass transition temperature of the polymer. Xray analysis of 30% DHEA micromatrices established the presence of crystalline DHEA in the micromatrices. The percent release of DHEA from the micromatrices, into 40% ethanol at 37°C, increased with increasing DHEA loading. The dissolution of DHEA from drug-polymer compressed discs of constant surface area was proportional to the square root of time indicating matrix controlled release.     

Preparation of dual-sensitive graft copolymer hydrogel based on N-maleoyl-chitosan and poly(N-isopropylacrylamide) by electron beam radiation

Organic solvent-soluble N-maleoyl-chitosan (NMCS) was synthesized by reaction of chitosan with maleic anhydride (MAH) in N, N-dimethylformamide (DMF). N-maleoyl-chitosan-graft-poly(N-isopropylacrylamide) (NMCS-g-PNIPAAm) copolymer hydrogel was prepared via free radical polymerization by electron beam (EB) irradiation. The copolymer obtained was analysed by FT-IR, XRD and thermal gravimetric analysis (TGA). It was found that the grafting yield and grafting efficiency increased with increasing radiation absorbed dose and monomer amount, and then decreased. The swelling ratio of the copolymer hydrogel was low at pH 4–5, and LCST of the hydrogel was around 32°C.     

Permeation of indomethacin from semisolid preparations through various semipermeable membranes

Objective: The aim of this study was to evaluate and compare the permeation of model drug indomethacin (IND) from various types of gels through several semipermeable membranes.

Methods: Permeation of IND from gels based on carbomer (CA), hydroxyethylcellulose (HEC), and polyacrylamid/laureth-7/isoparaffin was performed via diffusion cell method through membranes: shed snake skin, full thickness chicken skin, mucosa of pork small intestine, and cellophane.

Results: The least permeation of IND was observed in the case of shed snake skin and full thickness chicken skin. It did not exceed 5.4% of original amount in the preparation after 3?h of measurement regardless the type of gel. In the case of mucosa of pork small intestine and cellophane the permeated amount of IND ranged from 9.4 to 55.4% depending on the type of gelling agent used. There was also quite a significant influence of a gelling agent on the permeation of IND observed. The permeation of IND was highest from CA gel, where it ranged from 0.6 to 52.2% of original amount in the preparation depending on the type of membrane used. Gelling agent inhibiting the permeation the most was HEC, where the permeated amount of IND did not exceed 12.3% regardless the type of membrane used.

Conclusions: In general the permeated amount of IND through biological membranes containing stratum corneum represented just a small part of the amount in original preparation. Gelling agent has significant effect on the extent and rate of permeation.     

Rheological and thermal characteristics of a two phase hydrogel system for potential wound healing applications

Hydrogels fabricated from single polymers have been extensively investigated for wound healing applications. However, in many cases a single polymer cannot meet divergent demands in terms of both properties and performance. In this work, a two phase hydrogel was prepared by physically imbedding a xerogel in the core of a freeze thawed hydrogel. The outer hydrogel was prepared by freeze thawing poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) while the xerogels were prepared by UV polymerisation of 1-vinyl-2-pyrrolidinone (NVP). The rheological results indicated that the two phase hydrogels over a period of 2 weeks formed a strong interface and demonstrated greater physical strength. This suggested that the inner gel containing PVP diffused into the PVA/PAA hydrogel, which in turn increased hydrogen bonding, resulting in the overall increase in the stiffness of the gel. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirmed hydrogen bonding had occurred between the constituents of the two phase hydrogels. Thermal analysis suggested that T _g of each of the samples was above 80 °C, which indicated no impact on the behaviour of the gel at body temperature, but did however, give an indication of the stiffness of the dry polymer.     

Synthesis and self-assembly of pH-responsive chitosan graft copolymer by the combination of atom transfer radical polymerization and click chemistry

Amphiphilic chitosan-graft-poly(2-(N,N-diethylamino)ethyl methacrylate)-block-poly(ethylene oxide) (CS-g-(PDEAEMA-b-PEO)) copolymer was synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. The copolymer was characterized by ¹H NMR spectrum. The self-assembly and pH-responsive properties of CS copolymer were investigated by TEM, DLS, and transmittance in water. The micelle sizes can be adjusted through the alteration of the pH values of solutions. The presence of PEO segments can improve the hydrophilicity of the copolymer and avoid the excessive aggregation of the micelles. CS-g-(PDEAEMA-b-PEO) copolymer has both the unique properties of PDEAEMA-b-PEO and chitosan, and will have the potential applications in biomedical field.     

Characterisation of Biodegradable Microspheres Containing Dehydro-Iso-Androsterone

Poly-DL-lactide (PLA) and poly-DL-lactide-co-glycolide (DL-PGA) micromatrices (PharmazomesTM) containing dehydro-isoandrosterone (DHEA), a weak androgen, were prepared by a solvent evaporation process. Micromatrices with increasing drug loading as well as increasing polymer molecular weight were prepared. The morphology of these systems depended on the drug loading, the polymer molecular weight and polymer composition. Increasing the drug loading or polymer molecular weight resulted in increasingly irregular microparticles being formed. DSC thermograms did not reveal the presence of crystalline DHEA in micromatrices containing 10 to 50% DHEA loading. However crystalline DHEA was observed in microspheres heated to above the glass transition temperature of the polymer. Xray analysis of 30% DHEA micromatrices established the presence of crystalline DHEA in the micromatrices. The percent release of DHEA from the micromatrices, into 40% ethanol at 37°C, increased with increasing DHEA loading. The dissolution of DHEA from drug-polymer compressed discs of constant surface area was proportional to the square root of time indicating matrix controlled release.     

Preparation,properties, and drug release of thermo- and pH-sensitive poly((2-dimethylamino)ethyl methacrylate)/poly(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethylacrylamide) semi-IPN hydrogels

In this paper, a series of semi-interpenetrating polymer network (semi-IPN) hydrogels based on poly((2-dimethylamino)ethyl methacrylate)/poly (N,N-diethylacrylamide) (PDMAEMA/PDEA) were synthesized by changing the initial PDMAEMA/DEA molar ratio at room temperature. The influence of this additive on the property of resulting PDEA hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that the semi-IPN hydrogels have interconnected porous network structures. The glass transition temperature (T _g) of the semi-IPN hydrogels was observed by differential scanning calorimetry (DSC). Equilibrium swelling ratio (ESR), swelling and deswelling dynamics of the hydrogels responding to temperature and pH were investigated in detail. Compared to PDEA, the semi-IPN hydrogels exhibited excellent mutative values in response to an alternation of the temperature and pH, and showed fast swelling and deswelling rates in response to temperature and pH change. The release behaviors of the model drug, aminophylline, were found dependent on hydrogel compositions and environmental temperature. These results suggest that the stimuli semi-IPN hydrogel have potential application as intelligent drug carriers.     

Development of pH sensitive polyacrylamide grafted pectin hydrogel for controlled drug delivery system

In the present study an attempt was made to graft polyacrylamide on pectin. The grafted polymer was characterized by FTIR spectroscopy, differential scanning calorimetry and X-ray diffraction. Rheological property of pectin solution was compared with the product solution. The grafted polymer was cross-linked with varying amount of glutaraldehyde. The swelling properties of the cross-linked product were also studied. The salicylic acid, an antipyretic drug, was incorporated in the cross-linked gel as a model drug and the drug release studies were done in a modified Franz’s diffusion cell. The effect of cross-linking density on the release property of salicylic acid was studied through the cross-linked product. The product showed better film forming property and gelling property than pectin. The comparative rheological properties of pectin and grafted copolymer indicated change in the property of the product. FTIR studies indicated incorporation of amide group. Differential scanning calorimetry and XRD suggested formation of a new polymer. Swelling study indicated pH dependent swelling of the cross-linked hydrogel. Salicylic acid release indicated pH dependent release from the hydrogel.     

Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel

The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC_0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p?相似文献   

Graft copolymerization of 2-vinyl pyridine and styrene onto isotactic polypropylene powder by the preirradiation method

Preirradiated isotactic polypropylene (IPP) powder has been modified by grafting 2-vinyl pyridine (2-VP) and styrene (Sty) in an aqueous medium. The graft copolymerization reaction was studied under different experimental conditions such as total dose, monomer concentration, amount of the solvent, time of reaction and temperature to determine the optimum conditions for affording maximum percentage of grafting (P_g). Maximum grafting percent of 2-VP (180%) and styrene (117%) was obtained under optimum conditions. The rate of grafting (R_g) of 2-VP and styrene has also been determined as a function of total dose, initial monomer concentration and the reaction temperature. From maximum P_g and different R_g values of 2-VP and Sty, 2-VP is more reactive towards grafting as compared to styrene under optimum conditions. Characterization of the graft copolymers is based on differential scanning calorimetric (DSC) analysis. Isolation of the grafted poly(2-VP) and poly(styrene) chains from the grafted samples provides an additional evidence of formation of the graft copolymer.     

Antitumor activity of TNF-α after intratumoral injection using an in situ thermosensitive hydrogel

Local drug delivery strategies based on nanoparticles, gels, polymeric films, rods and wafers are increasingly used in cancer chemotherapy in order to enhance therapeutic effect and reduce systemic toxicity. Herein, a biodegradable and biocompatible in situ thermosensitive hydrogel was designed and employed to deliver tumor necrosis factor-α (TNF-α) locally by intratumoral injection. The triblock copolymer was synthesized by ring-opening polymerization (ROP) of β-butyrolactone (β-BL) and lactide (LA) in bulk using polyethylene glycol (PEG) as an initiator and Sn(Oct)₂ as the catalyst, the polymer was characterized by NMR, gel permeation chromatography and differential scanning calorimetry. Blood and tumor pharmacokinetics and in vivo antitumor activity of TNF-α after intratumoral administration in hydrogel or solution with the same dose were evaluated on S180 tumor-bearing mice. Compared with TNF-α solution, TNF-α hydrogel exhibited a longer T_1/2 (4-fold) and higher AUC_tumor (19-fold), but C_max was lower (0.5-fold), which means that the hydrogel formulation improved the efficacy with a lower systhemic exposure than the solution formation. In addition, TNF-α hydrogel improved the antitumor activity and survival due to lower systemic exposure than the solution. These results demonstrate that the in situ thermosensitive hydrogel-based local delivery system by intratumoral injection is well suited for the administration of TNF-α.     

Mechanical and thermal properties of poly(butylene terephthalate)/poly(ethylene naphthalate), and Nylon66/poly(ethylene naphthalate) blends

The tensile modulus, tensile strength and impact strength of melt blends of (a) poly(ethylene naphthalate) (PEN) and poly(butylene terephalate) (PBT) with 30, 40, 50, 60 and 70 wt% PEN, (b) Nylon66 and PEN with 30, 50 and 70 wt% Nylon66 were measured, and thermal/thermomechanical properties were analysed by differential scanning calorimetry and dynamic mechanical thermal analysis. Scanning electron microscopy was used for examination of the fracture surfaces of the blends.All PBT/PEN blends show two glass transitions corresponding to the presence of two phases: the glass transition temperature, T _g, of the phase with the lower T _g increases with increasing PEN content, and T _g for the phase with higher T _g decreases with increasing PBT content. The implication is that the two polymers are partially miscible, and scanning electron microscopy of fracture surfaces reveals a very small (sub-micron) domain size. Nylon66/PEN blends also show two phases, but the domain size is of the order of m and there is no evidence of partial miscibility.Up to 50 weight proportions PBT does not lower the tensile strength of PBT/PEN blends, and the tensile strength lies between values predicted by the rule of mixtures and a modified rule of mixtures. Incorporation of at least 40% PEN in PBT increases impact strength, but blending with smaller proportions of PEN decreases impact strength. By contrast, blending of Ny66 and PEN results in reduction of tensile strength for all blend compositions.     

Synthesis and characterization of a thermo-sensitive poly(N-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

Evaluation of carvedilol-loaded microsponges with nanometric pores using response surface methodology

This study demonstrates the use of factorial design for the preparation of microsponges of carvedilol with nanometric pores using the response surface methodology and to establish the functional relationships between two operating variables of Eudragit RS100 and sucrose. The response variables selected for this study were percent drug entrapment (Y1), time taken to release 35% of drug (Y2), percent drug release after 24?h (Y3), percent dissolution efficiency (DE) (Y4) and the angle of repose (Y5). The overall calculated desirability was found to be 0.8065 for the optimised formulation OF1. The response surface analysis of the desirability function with the independent levels indicated that the overall desirability increases with high levels of Eudragit RS100 and sucrose content. The optimum robust formulation (OF1) contains high levels of Eudragit RS100 (400.0?mg) and sucrose (350.21?mg), satisfying the predetermined constraints and goals of all the selected response variables. The scanning electron microscopy of OF1 indicated the spherical shape of microsponges with numerous pores on the surface. The atomic force microscopic study suggested the presence of nanometric pores on the surface of microsponges which may facilitate the release of the drug. Compatibility studies using the Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimeter indicated the absence of any incompatibility between carvedilol and excipients used to prepare microsponges.     

Polyacrylate (Eudragit Retard) Microspheres for Oral Controlled Release of Nifedipine. I. Formulation Design and Process Optimization

Abstract

Nifedipine was incorporated in polyacrylate-polymethacrylate microspheres using the solvent evaporation process. Optimal experimental conditions were found for the production of large batches of nifedipine microspheres based on Eudragit polymers the amount of which ranged from 25 to 40g. It was noted that the microspheres were net quite spherical and some of them especially the large microspheres, collapsed and lost their spherical shape due to the existence of internal void volume as evidenced by SEM examination of fractured nifedipine microspheres. It appeared that the experimental conditions used in the present study favoured the formation of microspheres of a new type. They could be defined as “film type” microspheres which consisted of spherical micromatrices comprizing an internal void space and a polymeric membrane of variable thickness where the nifedipine was dispersed either in a molecular or solid state depending on the payload extent. This was confirmed by differential scanning calorimetry analysis and scanning electron microscopy which detected drug crystals embedded on the microsphere surfaces at high drug content.     

Development of Cellulose Eco‐nanocomposites with Antimicrobial Properties Oriented for Food Packaging

Nanocomposites based on cellulose acetate, a commercial organoclay (Cloisite30B), triethyl citrate and variable content of antimicrobial agents (thymol and cinnamaldehyde), were obtained using a solution casting technique. The properties of the nanocomposites were evaluated using X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, mechanical (modulus of elasticity, tensile strength and elongation at break), scanning electronic microscopy, global migration and microbiological testing. A reduction of glass transition (T_g), melting temperature (T_m) and melting enthalpy (?H_m) was also observed when the content of thymol and cinnamaldehyde was increased in the cellulose acetate nanocomposites. In contrast, thermal stability, mechanical performance and morphology of material did not show important differences when the content was modified. Results of global migration were dependent of the kind of simulant used. Finally, the antimicrobial activity was dependent of the essential oil used and its content inside the nanocomposite. An important effect of organoclay on the antimicrobial activity was also observed. Copyright © 2012 John Wiley & Sons, Ltd.     

Relaxation behaviour of the amorphous components of wood

The viscoelastic properties of mod were investigated using dynamic mechanical thermal analysis and differential scanning calorimetry. Under a limited set of conditions, two separate glass transitions (T _g) could be identified with both techniques. These two transitions were identified as arising from the amorphous lignin and hernicellulose matrix in the wood cell wall. Moisture dramatically affected the temperature at which the two dispersions occurred and, consequently, the ability to resolve their independent responses. The relationship betweenT _g and moisture for both components could be modelled with the Kwei equation, which accounts for the presence of secondary interactions. Annealing and specific interactions of a series of organic diluents were wed in an attempt to enhance the resolution of the two components values ofT _g. Time-temperature superposition was shown to be applicable to wood plasticized with ethyl formamide, following Williams-Landel-Ferry behaviour over the temperature rangeT _g toT _g + 85° C. These observations allow certain conclusions to be drawn concerning the applicability of existing models of the wood cell wall's supermolecular morphology. Most notably, models of thein situ morphology of the three wood components can be limited to those which consider the amorphous matrix of lignin and hemicellulose to be immiscible.     

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.     

Release of Ciprofloxacin from Chondroitin 6-Sulfate-Graft-Poloxamer Hydrogel In Vitro for Ophthalmic Drug Delivery

The system was designed to use Poloxamer as a vehicle for ophthalmic drug delivery using in situ gel formation property. To enhance the wound healing and cell adhesion as well as transparency of Poloxamer hydrogel, chondroitin 6-sulfate (C6S) was introduced into Poloxamer. For this purpose, mono amine-terminated Poloxamer (MATP), which was end-capped with ethylene amine group only in one side of terminal hydroxyl groups of Poloxamer, was synthesized. Subsequently, C6S-graft-Poloxamer copolymer (C6S-g-Poloxamer) was prepared by reaction between the amine groups of MATP and carboxyl groups of C6S in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carboimide (EDC). The coupling of MATP with C6S was clarified by ¹H-NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was determined by measuring the temperature at which immobility of the meniscus in each solution was first noted. Release behavior of ciprofloxacin from C6S-g-Poloxamer hydrogel in vitro was investigated as a function of C6S content in the graft copolymer by a spectrophotometric assay at 287 nm using an UV spectrophotometer. Differences in the adhesion and morphology of human lens cell between Poloxamer- and C6S-g-Poloxamer-coated surfaces were also investigated. The gelation temperatures of C6S-g-Poloxamer copolymers were lowered with increasing of the concentration of the copolymer and decreasing of C6S content. The release of ciprofloxacin from the graft copolymer was sustained compared with Poloxamer itself and decreased with increasing the content of C6S in the copolymer due to the in situ gel formation of the copolymer and viscous properties of C6S. Human lens cells (B3) adhered to C6S-g-Poloxamer-coated surface were observed as transformed shapes after 2 days. The bioadhesive and thermally gelling of these graft copolymers will be expected to be an excellent drug carrier for the prolonged delivery to surface of the eye.