Preparation and drug‐release behavior of minocycline‐loaded poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] films

In this work, biocompatible hydrogel matrices for wound‐dressing materials and controlled drug‐release systems were prepared from poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] [p(HEMA‐co‐PEG–MA] films via UV‐initiated photopolymerization. The characterization of the hydrogels was conducted with swelling experiments, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (differential scanning calorimetry), and contact‐angle studies. The water absorbency of the hydrogel films significantly changed with the change of the medium pH from 4.0 to 7.4. The thermal stability of the copolymer was lowered by an increase in the ratio of poly(ethylene glycol) (PEG) to methacrylate (MA) in the film structure. Contact‐angle measurements on the surface of the p(HEMA‐co‐PEG–MA) films demonstrated that the copolymer gave rise to a significant hydrophilic surface in comparison with the homopolymer of 2‐hydroxyethyl methacrylate (HEMA). The blood protein adsorption was significantly reduced on the surface of the copolymer hydrogels in comparison with the control homopolymer of HEMA. Model antibiotic (i.e., minocycline) release experiments were performed in physiological buffer saline solutions with a continuous flow release system. The amount of minocycline release was shown to be dependent on the HEMA/PEG–MA ratio. The hydrogels have good antifouling properties and therefore are suitable candidates for wound dressing and other tissue engineering applications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Interaction between the fluorinated amphiphilic copolymer poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐graft‐poly(SPEG) and DNA

A synthesized copolymer, synthesized from HFMA (hexaflurobutyl methacrylate) and SPEG (PHFMA‐g‐PSPEG), was synthesized. PHFMA‐g‐PSPEG intercalated to the DNA base pair via a strong hydrophobic force, and this was conformed by ultraviolet spectroscopy, transmittance measurements, micropolarity measurements, resonance light scattering (RLS) spectroscopy, and particle size measurements. The copolymer was used as a new probe to detect DNA according to the RLS technique. The hydrophobic interaction between PHFMA‐g‐PSPEG and DNA significantly enhanced the RLS signal, and the enhanced RLS intensity at 422 nm was proportional to the nucleic acid concentration within the range of 0.09–0.90 mg/L with a detection limit (3σ) of 4.0 μg/L. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Preparation of bioactive glycosylated glial cell‐line derived neurotrophic factor‐loaded microspheres for medical applications

Poly (lactic‐co‐glycolic acid) (PLGA)‐coated gelatin microspheres containing glial cell‐line derived neurotrophic factor (GDNF) were developed by thermal gelation through a water‐in‐oil emulsion technique. Gelatin types (A and B) at four different pH levels were investigated for their influences on the morphology, the microsphere size, the zeta potential, and the swelling ability. The encapsulation of GDNF and the release characteristics of GDNF were also determined using enzyme‐linked immunosorbent assay (ELISA). The maximum cumulative released amounts of GDNF from the microspheres were increased from 50 to 90% after 4 d (based on the actual amount of the GDNF). Thus, the release of the GDNF contents in the microspheres depends on the amount of GDNF. Trigeminal ganglion cells (TGCs) were used to study the bioactivity of GDNF released from the microspheres, which was proven to retain its bioactivity in promoting the TGCs' neurite outgrowth. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40167.     

Preparation of poly(L‐lactide) microparticles by a supercritical antisolvent process with a mixed solvent

Poly(L ‐lactide) (PLLA) microparticles were prepared by a supercritical antisolvent (SAS) process with a mixed solvent. Five factors, namely, the molar percentage of acetone, pressure, temperature, flow rate, and concentration of the solution, were optimized by a four‐level orthogonal array design. By analysis of variance, the concentration of the solution showed a significant effect on the PLLA microparticle size. The effects of the mixed solvent (dichloromethane/acetone) at different mixing ratios, pressures, and temperatures on the morphology of the PLLA microparticles were also investigated. The thermal properties of PLLA before and after the SAS process were studied by differential scanning calorimetry. The results indicate that the molar percentage of acetone had a significant effect on the morphology of the PLLA microparticles. The microparticles prepared with the mixed solvent were much smaller than those prepared with dichloromethane alone under the same conditions. Furthermore, the particle size distribution was more uniform in the case of the mixed solvent. The particle size decreased with increasing pressure, whereas it showed no significant change with increasing temperature. The results also show that the thermal properties of PLLA could be improved through the SAS process. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

Mixed‐interpenetrated polymeric networks based on sodium alginate (ALG) and poly(N‐isopropylacryl amide) (PNIPAAm) covalently cross‐linked with N,N'‐methylenebisacrylamide are studied for their biocompatibility, nontoxicity, and biodegradability aiming their application in drug delivery. The presence of drug‐polymeric matrix interactions and the distribution of the drug in the polymeric network for theophylline‐loaded ALG/PNIPAAm hydrogels are also investigated by spectroscopic and microscopic methods. The quantitative evaluation of theophylline loaded hydrogels performed by NIR‐CI technique shows a better drug entrapment and a higher homogeneity of the samples with increased alginate content. The thermal behavior of the hydrogels is significantly modified by theophylline presence. The application of the ALG/PNIPAAm hydrogels as carriers for sustained drug release formulations was assessed by the theophylline release tests performed both by in vitro and in vivo studies. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40733.     

Synthesis and properties of a new type of unsaturated poly(ester amide)

A new type of unsaturated poly(ester amide), maleic anhydride–phthalic anhydride–ethylene glycol–neopentylene glycol–anthranilic acid copolymer, was prepared by melt polycondensation. The copolymer was characterized by Fourier transform infrared spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The viscosity of the polymer was measured with a Ubbelohde viscometer. The compressive strength of the crosslinked unsaturated poly(ester amide) under different heat‐treatment conditions was measured. Studies of its degradation behavior were carried out in simulated body fluid at pH 7.4 (37°C), and the compressive strength loss of the crosslinked unsaturated poly(ester amide) was also measured after different degradation times. The copolymer was hydrolyzed in a 1.0‐mol/L NaOH standard solution at room temperature. All of the preliminary results suggest that the new unsaturated poly(ester amide) might potentially be used as a new type of bone‐fixation material. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Intramolecular and intermolecular crosslinked poly(vinyl alcohol)–borate complexes for the sustained release of fertilizers and enzymes

Therapeutic agents or agricultural fertilizers captured in polymer colloids (PCs) give rise to interesting applications, which are typically related to sustained release. We synthesized crosslinked polymer structures with poly(vinyl alcohol) (PVA) and borax precursors. Fourier transform infrared spectroscopy showed that a polymer–boron ion complex was formed with the crosslinking reaction at the O H site of PVA; thereby, PCs were formed. Field‐emission scanning electron microscopy showed that a uniform mesoporous two‐dimensional structure formed via intermolecular and intramolecular crosslinking. Trypsin enzyme and phosphate fertilizer were trapped in these PCs independently to study sustained release. Fertilizer‐incorporated PCs were mixed with soil samples, in which seeds of fenugreek were sown, and the plant growth was monitored a duration of 15 days. The fertilizer release, studied with UV–visible spectroscopy, showed a sustained signature of the fertilizer (at 690 nm) in the water extracts of soil, with much healthier plant growth compared to the control. For the trypsin‐incorporated PC samples, the released enzyme was made to interact with bovine serum albumin protein to monitor the released percentage with UV absorption spectroscopy. A systematic increase in the enzyme signature (at 280 nm) was observed for a duration of 60 min; this indicated the potential of PC for sustained drug release. The swelling calculations predicted that the mechanism involved was composed of pseudo‐swelling behavior. We envisaged that the hydroxyl groups of the PC broke in water and formed a complex with water. This complex slowly dissolved in water to release the entrapped molecules. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Cephazoline sodium release from poly(N‐isopropyl acrylamide‐co‐N,N‐dimethylacrylamide) hydrogels

Hydrogels are hydrophilic polymers that swell to an equilibrium volume in the presence of water, preserving their shape. The dynamic swelling behavior of poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) [poly(NIPA‐co‐DMA)] copolymers at 37°C was investigated. It was observed that the swelling degree in the copolymers decreases with the N‐isopropylacrylamide content. In addition, the liberation mechanism was found to be Fickian. Diffusion coefficients according to Fick′s law as a function of the N‐isopropylacrylamide concentration and results of the release process are reported. The kinetics of cephazoline sodium release from poly(NIPA‐co‐DMA) hydrogels with different compositions was studied. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3433–3437, 2004     

Poly(N‐isopropylacrylamide) hydrogel: Effect of hydrophilicity on controlled release of ibuprofen at different pH

Stimuli‐sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermo‐sensitive DDS dealing with poly(N‐isopropylacrylamide) (PNIPAM) have been widely studied. Hydrogels composed of temperature‐sensitive NIPAM and biocompatible and pH‐sensitive maleic acid (MAc) were synthesized by sedimentation polymerization. Experiments on drug release from the crosslinked NIPAM‐co‐MAc hydrogel loaded with ibuprofen into different pH buffer solutions were successfully carried out at temperature swing between 25 and 40°C. The in vitro release studies have showed that the release rate depended on acidity or basicity (polarity) of the medium and the gel and swelling ratio of the gel network as a function of the environmental pH and temperature. The SEM image of the dry bead gave more insight into the surface architecture and the thermal studies shine light on the decomposition pattern and glass transition temperature of the gel. The mechanism of the drug release was discussed in relation to the diffusion rate and the abrupt change in the pH of the medium. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Sustained release behavior of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogels containing activated carbon fibers

The composites of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel and activated carbon fibers (ACFs) were prepared as sustained drug release system with excellent mechanical properties. The mechanical properties of hydrogels were improved greatly by addition of ACFs. The thinner ACFs were more effective in increasing the mechanical properties of composite hydrogels. The cumulative amount of release and the release period were dependent on the surface area and the pore volume of ACFs. The drug release was maximized at basic condition due to the pH‐sensitive hydrogel matrices and the initial bust phenomenon was alleviated by incorporating ACFs in the hydrogels. The drug release was sustained about four times longer and the mechanical property was increased about 2.6 times higher because ACFs worked as drug reservoir and reinforcement. Cytotoxicity evaluation confirmed the biocompatible characteristics of the ACFs‐containing hydrogels. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and in vitro drug‐release behavior of 5‐fluorouracil‐loaded poly(hydroxybutyrate‐co‐hydroxyhexanoate) nanoparticles and microparticles

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) copolymeric microparticles (MPs) and nanoparticles (NPs) were prepared by the double‐emulsion solvent‐evaporation technique. 5‐Fluorouracil (5‐Fu), an anticancer drug, was entrapped in PHBHHx NPs and MPs. A variety of parameters, including the species and concentration of different surfactants, power and time of ultrasonication for particle dispersion, and organic/aqueous solution ratio, that affected the production of the 5‐Fu‐loaded PHBHHx NP and MP particles and the release of 5‐Fu were studied. The results show that the prepared NPs and MPs were spherical in shape and about 160 nm and 3 μm in size, respectively, when cetyltrimethyl ammonium bromide was used as the emulsifier. The drug‐loading content (DLC) varied from 3.53 to 8.03% for 5‐Fu‐loaded NPs and from 4.83 to 18.87% for 5‐Fu‐loaded MPs and depended on the different initial feeding amounts of 5‐Fu. The encapsulation efficiency decreased with increasing DLC. The in vitro drug‐release characteristics appeared to have two phases with an initial burst effect occurring within the first 8 h; this was more obvious for the particles with low DLCs. The NPs with high DLC (8.03%) had the slowest release rate, 49.6% of 5‐Fu within 24 h. Therefore, PHBHHx copolymeric NPs and MPs can possibly be applied as drug‐delivery carrier materials in the future. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

Layer‐by‐layer assembly of poly(allylamine hydrochloride)/polyurethane and its loading and release behavior for methylene orange

Here, layer‐by‐layer technique was used for sequential adsorption of oppositely charged polymer poly(allylamine hydrochloride) (PAH) and polyurethane (PU) through electrostatic interaction. 10 and 10.5 bilayer films were prepared separately, methylene orange (MO) was used as a model drug to evaluate the potential ability of this multilayer film used in drug delivery system. Experimental results showed the ability of loading and release of MO from the film was significantly influenced by pH and salt concentration, the loading rate of MO was faster and larger with increasing salt concentration or decreasing pH of MO solution, the release rate of MO was faster at higher salt concentration or in alkali solution. The result also indicated that the film had a good reversibility of loading and release. PAH/PU film could be a promising drug delivery system because of its biocompatibility, biodegradation and above properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Carboxymethylcellulose–Chitosan‐coated microneedles with modulated hydration properties

Microneedles containing sodium carboxymethylcellulose (CMC) formulations were fabricated to include an external chitosan (CS) layer to modulate their hydration profile, an important parameter affecting their application as intradermal delivery devices and their storage. The microfabrication process was carried out under conditions that enabled the formation of polyelectrolyte complexes between these oppositely charged macromolecules. CMC–CS microneedles were characterized by water uptake in a humid environment, contact angle measurements, dissolution in aqueous solutions, and protein‐release profiles. The results demonstrate that the microneedles containing CMC–CS formulations displayed suppressed moisture sensitivity in water vapors compared to their unmodified CMC counterparts while the maintaining quick protein‐release characteristics required for their uses. This approach also showed the potential for sustained protein‐release applications, as the CMC–CS formulations could be combined in layers to fabricate multicompartment microneedle coatings with delayed release characteristics. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Hydroxypropylmethyl cellulose‐based sponges loaded self‐microemulsifying curcumin: Preparation,characterization, and in vivo oral absorption studies

Novel hydroxypropylmethyl cellulose (HPMC)‐based sponges containing self‐microemulsifying curcumin (SME‐Cur) were prepared by a freeze drying method using different grades of HPMC (E5 LV, E15 LV, E50 LV, A15 LV, and A4C). The physical properties and drug release from these carriers were characterized and compared among the different formulations. The mean pore size values of the sponges from image analysis ranged from 43.36 ± 4.54 to 123.22 ± 8.19 nm. An increase in the concentration or viscosity of the HPMC, resulted in denser sponges and a slower drug release. The average microemulsion droplet size from the optimal sponge formulation was 34.80 ± 0.1 nm, and the curcumin was almost completely released within 120 min. The AUC after oral administration of the liquid and solid SME‐Cur were 7‐ and 5‐fold greater than that of the curcumin powder in the rabbit, respectively. The results demonstrated that the HPMC‐based sponges loaded with SME‐Cur could be efficiently used to enhance the oral bioavailability and might be useful as they could be administered at a lower dose compared to normal curcumin powder. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42966.     

Fabrication of polymeric nanoparticles of poly(ethylene‐co‐vinyl acetate) coated with chitosan for pulmonary delivery of carvedilol

Carvedilol is a drug with low oral bioavailability due to its high first‐pass metabolism. The purpose of the present study was to prepare a mucoadhesive dry powder inhaler of this drug loaded in poly(ethylene‐co‐vinyl acetate)(PEVA) nanoparticles for pulmonary delivery. PEVA nanoparticles were prepared by an O/W solvent evaporation method and coated with different concentrations of chitosan as a mucoadhesive polymer. Encapsulation efficiency, particle size, zeta potential, release efficiency, and mucoadhesive properties of the different formulations were evaluated on mucin substrate. The optimized formulation of nanoparticles was spray dried using lactose and mannitol as carrier powders. The flowability of the obtained powders was checked by Carr's Index and Hausner ratio and the in vitro deposition of the aerosolized drug was investigated using a Next Generation Impactor. Increasing in the particle size and zeta potential of nanoparticles confirmed the settling of the chitosan coating layer on the surface of nanoparticles. The in vitro drug release from coated nanoparticles decreased with increasing of chitosan concentration. Mucoadhesive property of chitosan‐coated PEVA nanoparticles was higher than noncoated ones. Spray‐dried powders had different aerosilization behavior. Mannitol‐based formulation was found to have low density, better flow ability, smaller aerodynamic diameter (d_aer) and higher fine powder fraction. The results of the present study allow concluding that mannitol spray dried, mucoadhesive nanoparticles of PEVA are suitable inhaler powder for pulmonary delivery of carvedilol. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39694.