Poly(dimethylsiloxane) coatings for controlled drug release. II. Mechanism of the crosslinking reaction in emulsion

Earlier work focused on the crosslinking of hydroxyl‐terminated poly(dimethylsiloxane) (PDMS) particles in a stable latex suitable for spraying onto drug tablets, and established the conditions for eliminating the usual toxic catalysts that would be unacceptable in such pharmaceutical coating materials. Use of these coatings for controlling the rate of release of a drug, however, requires a better understanding of their properties and thus clarification of the mechanism through which the crosslinking occurs. The present study approaches this goal by documenting the effects of anionic, cationic, and nonionic surfactants at various concentrations, and in acidic, neutral, or basic media. FTIR spectroscopy was used to monitor the transportation of crosslinker from the water phase into the hydrophobic PDMS phase. The results suggest a possible mechanism for the crosslinking in sufficient detail to be used to optimize the coatings for drug‐release applications. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2186–2194, 2004     

Poly(dimethylsiloxane) coatings for controlled drug release. III. Drug release profiles and swelling properties of the free‐standing films

Previous reports in this series have described the preparation of stable poly(dimethylsiloxane) (PDMS) latices suitable for spray‐coating of drug tablets, as well as the mechanism of associated crosslinking reactions in PDMS emulsions. In the present investigation, in vitro evaluations were performed to study the effects of the amount of channeling agents, the addition of colloidal silica, and the pH of the dissolution media used. The study involved hydrochlorothiazide (as a marker drug) released from compressed tablets, which had been spray coated using PDMS latices with various polyethylene glycol (PEG) loadings as channeling agents. The dissolution results showed that coated tablets containing up to 25% (w/w dps) PEG could have constant release rates. Higher amounts of PEG resulted in nonlinear release patterns. The addition of colloidal silica decreased the rates of drug release. The pH of dissolution media affected the structures of the exposed PDMS films. Swelling tests were carried out to determine water uptake. Scanning electron microscopy and density measurements showed that the films obtained after soaking in higher‐pH media were more condensed, with corresponding changes in drug‐release rates. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 494–501, 2005     

Preparation of five-membered bis(cyclic carbonate)s at atmospheric pressure for polyhydroxyurethane coatings

Cyclic carbonates reacted with diamines or polyamines have been proposed as a greener and safer method to prepare free isocyanate polyurethane coatings. Here, five kinds of bis(cyclic carbonate)s (TDC: toluene bis(cyclic carbonate), MDC: 4,4′-diphenylmethane bis(cyclic carbonate), IPDC: isophorone bis(cyclic carbonate), HMDC: 4,4′-methylenebis(cyclohexyl cyclic carbonate), HDC: hexamethylene bis(cyclic carbonate)) were prepared by reacting glycerol carbonate with diisocyanate under atmospheric pressure. Their structures were verified by ¹H-NMR and ¹³C-NMR. These difunctional cyclic carbonates were then reacted with several amines to prepare new polyhydroxyurethane (PHU) coatings, and the film properties were tested. It was found that PHUs based on aromatic and alicyclic structures including TDC, MDC, IPDC, and HMDC displayed high hardness but had poor flexibility and impact resistance, whereas PHUs based on aliphatic structures such as HDC exhibited good flexibility and impact resistance and low hardness. When the length of the alkyl groups in the amine curing agents increased, the impact resistance and flexibility of the PHUs increased, but their pencil hardness decreased. PHUs from TDC, MDC, and IPDC had excellent chemical resistance, but the PHUs from HMDC and HDC had less chemical resistance. Some films displayed excellent properties including 4H pencil hardness, 100 cm kg impact resistance, and excellent flexibility. Some PHUs exhibited good thermal stability, with T_5% values all above 242°C. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47957.     

Preparation and characterization of poly(vinyl alcohol) and 1,2,3‐propanetriol diglycidyl ether incorporated soy protein isolate‐based films

Novel biodegradable films were prepared from soy protein isolate (SPI), poly(vinyl alcohol) (PVA), glycerol, and 1,2,3‐propanetriol diglycidyl ether (PTGE). The mechanical, hydrophilic, and compatible properties of the films were investigated. The influence of PTGE as a crosslinker on the properties of the SPI/PVA/PTGE films was examined with Fourier transform infrared spectroscopy, X‐ray diffraction (XRD), thermogravimetric analysis, mechanical analysis, contact angle measurements, and scanning electron microscopy. XRD and contact angle examination confirmed that the addition of PTGE altered the film microstructure to a crystalline one. The mechanical properties and water resistance of the SPI/PVA/PTGE films increased notably compared with those of the unmodified SPI films. All results indicate that the networks were formed between SPI and PTGE and played an important role in forming a homogeneous structure in the obtained films. The novel biodegradable films provide a convenient and promising way for preparing environmentally friendly film materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42578.     

Properties of chitosan/poly(vinyl alcohol) films for drug‐controlled release

With bovine serum albumin (BSA) as a model drug, drug‐loaded films of chitosan (CS) and poly(vinyl alcohol) (PVA) were obtained by a casting/solvent evaporation method and crosslinked by tripolyphosphate (TPP). The films were characterized by FTIR, XRD, and SEM. The influential factors of drug‐loaded films on drug‐controlled release were studied. These factors included, primarily, the component ratio of CS and PVA, the loaded amount of BSA, the pH and ionic strength of the release solution, and the crosslinking time with TPP. The results showed that within 25 h, when the weight ratios of CS to PVA in the drug‐loaded films were 90 : 10, 70 : 30, 50 : 50, and 30 : 50, the cumulative release rates of BSA were 63.3, 72.9, 81.8, and 91.8%, respectively; when the amounts of model drug were 0.1, 0.2, and 0.3 g, the release rates were 100, 81.8, and 59.6%, respectively; when the pH values of the drug release medium were 1.0, 3.8, 5.4, and 7.4, the release rates reached 100, 100, 37.9, and 7.8%, respectively; the cumulative release rates of BSA were 78.4, 82.3, 84.3, and 91.7% when the ionic strengths of the release solution were, respectively, 0.1, 0.2, 0.3, and 0.4M; when the crosslinking times of these drug films in the TPP solution were 0, 5, 15, 30, and 60 min, the release rates attained 100, 100, 81.8, 65, and 43.3%, respectively. All the results indicated that the CS/PVA film was useful in drug delivery systems. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 808–813, 2005     

聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展

聚天冬氨酸是一种新型的聚合氨基酸材料,具有很好的生物相容性、生物降解性。本文综述了聚天冬氨酸及其衍生物水凝胶的研究现状,介绍了化学交联、光交联、γ射线交联3种交联方法合成的聚天冬氨酸及其衍生物水凝胶,以及近年来聚天冬氨酸基凝胶对大分子蛋白药物、小分子抗炎性药物、抗癌和基因药物控释的研究进展,并对该凝胶在药物控释领域的发展方向进行了预测。     

Preparation and characterization of multilayer anti-reflective coatings via sol-gel process

Single layer and multilayer films consisting of SnO₂, Ta₂O₅, SiO₂, TiO₂, indium tin oxide (ITO) and antimony tin oxide (ATO) have been prepared by sol-gel dip coating technique. All of the multilayer films contained a SiO₂ top layer, which was composed of SiO₂ nanoparticles. The other films had polymeric character. Obtained films were characterized by ellipsometry, XRD, AFM and SEM. Light transmittance values of the films were compared. Films other than SiO₂ and Ta₂O₅ were found to have crystalline structure. Thickness values of the films were in the range of 30–115 nm and roughness values were in 1.2–23 nm range. Single layer porous silica provided 95% light transmittance, whereas ITO-TiO₂-SiO₂ multilayer film provided a light transmittance of 97.2%.     

Synthesis,structure, and mechanical properties of castor oil‐based polyamidoamines toughened epoxy coatings

A series of toughened epoxy systems was prepared via crosslinking of diglycidyl ether of bisphenol A with castor oil‐based polyamidoamines as curing agents. To this aim two series of polyamidoamines were synthesized in two steps from the reaction of castor oil with triethylenetetramine and then reaction of these products with dissolved salicylic acid in dimethyl formamide (DMF). The structure of the compounds was confirmed by FTIR spectra, GC‐Mass and ¹H‐NMR spectroscopy. The mechanical properties, adhesion and water resistance of polyamine and polyamidoamines cured epoxy systems were studied. It was found that significant improvement in toughness and adhesion of the epoxy films was achieved by using polyamidoamines as curing agents. The results showed a great enhancement in toughness and adhesion properties of the epoxy coats proportional to increasing castor oil weight ratio, and/ or using salicylic acid and DMF. Furthermore, polyamidoamines cured samples showed higher water resistance and less degradation in hot water immersion tests than polyamine cured samples. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation of resistant starch/poly(vinyl alcohol) blend films with added plasticizer and crosslinking agents

We report on the physical properties of films synthesized with native corn starch (NCS) and resistant starch (RS4) prepared with NCS. NCS and RS4/poly(vinyl alcohol) (PVA) blend films were synthesized with a mixing process and casting method. Glycerol (GL) and citric acid (CA) were used as additives. Glutaraldehyde (GLU) was used as a crosslinking agent of the films. RS4 was synthesized with sodium trimetaphosphate and sodium tripolyphosphate as a crosslinker. Then, the RS4 thus synthesized was confirmed by the pancreatin–gravimetry method, swelling power, differential scanning calorimetry, and X‐ray diffraction. The tensile strength, elongation, swelling behavior, and solubility of the films were measured. The results of the measurements indicated that the RS4‐added film was better than the NCS‐added film. In particular, the RS4/PVA blend film with CA as an additive showed physical properties superior to those of the other films. Also, the physical properties with GLU added as a crosslinking agent to the films were investigated. With increasing GLU contents, the tensile strength increased but the elongation, swelling behavior, and solubility values of the GL‐added and CA‐added films decreased. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation and characterization of graphene oxide reinforced PVA film with boric acid as crosslinker

PVA films were prepared through aqueous solution method, and boric acid (BA) as well as graphene oxide (GO) was added to improve the mechanical and thermal properties. It was found that 5 wt % BA could increase the tensile strength threefold (from 23.3 to 67.7 MPa), and the incorporation of 0.2 wt % GO would provide additional percentage growth of 30% (from 67.7 to 88.5 MPa). Moreover, an enhancement of thermal stability of PVA film was found when BA or GO filler was added. The reinforcement mechanisms of both BA and GO were investigated, and a competitive phenomenon that the addition of BA would influence the reinforcement effect of GO sheets was found. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42000.     

Semi-solid materials for controlled release drug formulation: current status and future prospects

Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semisolid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.     

Preparation and characterization of RDX based composite energetic materials with a cellulose matrix

Cyclotrimethylenetrinitramine (RDX)-based high-energy explosives are widely used in weapon warheads, propellants, and ammunition. Many studies have explored different supporting structures for RDX; however, the use of natural materials have rarely has been reported. Natural cellulose is widely known for its excellent compatibility and loading capacity. In this study, cellulose was used as a supporting structure and insensitive material for RDX composites. Cellulose/RDX composite aerogels (RCAs) were prepared using 1-allyl-3-methyl imidazole (AMIMCl) as the solvent, and their properties were characterized. The results show that the content of nitrogen in cellulose/RCAs was 34.5%, and the content of RDX was as high as 94.3%. Moreover, RDX particles were attached to the fibers inside the cellulose aerogels (CAs), forming a homogeneous protective layer on the surface of the cellulose matrix. Compared with the raw RDX material, the thermal stability of the cellulose/RDX energetic aerogels was greatly increased. The porosity of the CAs was reduced due to RDX particles growing inside the CAs. The impact sensitivity increased from 35 to 78 cm.     

Evaluation of mechanical properties and hydrophobicity of room-temperature,moisture-curable polysilazane coatings

Polysilazane coatings have a broad need in real-life applications, which require low processing or working temperature. In this work, five commercially available polysilazanes have been spin-coated on polycarbonate substrates and cured in ambient environment and temperature to obtain transparent, crack-free, and dense films. The degree of crosslinking is found to have a significant impact on the hardness and Young's modulus of the polysilazane films but has a minor influence on the film thickness and hydrophobicity. Among all five polysilazane coatings, the inorganic perhydropolysilazane-based coating exhibits the largest hardness (2.05 ± 0.01 GPa) and Young's modulus (10.76 ± 0.03 GPa) after 7 days of curing, while the polyorganosilazane-derived films exhibit higher hydrophobicity. The molecular structure of polysilazanes plays a key role in mechanical properties and hydrophobicity of the associated films, as well as the adhesion of coatings to substrates, providing an intuitive and reliable way for selecting a suitable polysilazane coating material for a specific application.     

壳聚糖/聚羟基丁酸戊酸共聚酯生物降解复合膜的制备

以冰乙酸为溶剂,将壳聚糖（CS）与聚3-羟基丁酸-co-3-羟基戊酸共聚酯（PHBV）采用共混流延法制备成CS/PHBV生物降解复合膜。采用扫描电镜、傅里叶变换红外光谱对复合膜进行了表征,并研究了不同质量比CS/PHBV复合膜的力学性能、透氧性能、热稳定性以及生物降解性能。结果表明：随着壳聚糖含量的增加,复合膜断面密实,蜂窝状结构消失,复合膜中羟基和酯基增多;当m_CS∶m_PHBV为3∶1时,CS/PHBV生物降解复合膜的拉伸强度与弹性模量达到最大值,分别为3.57和26.84 MPa;当m_CS∶m_PHBV为4∶1时,复合膜的透氧系数最小,为27.7×10^-15 cm³·cm/（cm²·s·Pa）;同时,壳聚糖的加入,提高了CS/PHBV复合膜的生物降解性。     

Dextrin crosslinked with poly(lactic acid): A novel hydrogel for controlled drug release application

A new class of biodegradable crosslinked hydrogel, consisting of hydrophobic polylactic acid (PLA) and hydrophilic dextrin in presence of crosslinker N,N‐methylene bisacrylamide (MBA) has been synthesized by free‐radical polymerization technique using potassium persulfate (KPS) as initiator. By variation of crosslinker concentration, a series of hydrogels have been prepared and the optimized grade has been selected on the basis of higher crosslinking efficiency as well as lower equilibrium swelling characteristics, XRD analysis. The hydrogels have been characterized by FTIR spectra, ¹³C‐NMR spectra, CHN analysis, SEM analysis, swelling characteristics, and toxicity study. In vitro release study of model drugs (ciprofloxacin and ornidazole) from hydrogel matrix has been performed in various buffer solutions at 37°C. The drug release kinetics and mechanism have been studied using zero order, first‐order kinetic models, Korsemeyar–Peppas model, Higuchi model, Hixson–Crowell model, and nonlinear Kopcha model. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40039.     

Poly(N-isopropylacrylamide)/mesoporous silica thermosensitive composite hydrogels for drug loading and release

Temperature-sensitive hydrogels are attracting increasing attention for controlled drug delivery. However, achieving high drug loadings and sustained drug release remains challenging. Herein, we describe the successful synthesis of a series of novel temperature-sensitive poly(N-isopropylacrylamide) (PNIPA)/mesoporous silica nanoparticles (MSN) hydrogels by physical crosslinking of NIPA with MSN. The external and internal structures, temperature sensitivity, drug-loading capacity, and blood compatibility of the PNIPA/MSN composite hydrogels are studied. Results show that MSN addition improved the network structure and adjusted the size of the hole, MSN could also act as drug carrier, thereby enhancing the drug loading capacity. The composite hydrogels underwent a phase transition at 33.7 °C (at the lower critical solution temperature). The hemolysis rate of the composite hydrogels was less than 1%, thus they can be classified as a nonhemolytic materials with good biocompatibility. The composite hydrogels reported here thus have great potential in drug transport and temperature-activated drug release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48391.     

Preparation and properties of poly(urethane acrylate) films for ultraviolet‐curable coatings

Four different UV‐curable poly(urethane acrylate)s were prepared through the reaction of two diisocyanates [i.e., toluene‐2,4‐diisocyanate (TDI) and isophorone diisocyanate (IPDI)] and two polyols [i.e., polycaprolactone triol (PCLT) and polycaprolactone diol (PCLD)], and they were characterized with Fourier transform infrared spectroscopy. The mechanical properties, thermal properties, and water sorption of the cured poly(urethane acrylate)s were also investigated with respect to the chemical structures of the polyols and diisocyanates. In comparison with linear PCLD–TDI and PCLD–IPDI, crosslinked PCLT–TDI and PCLT–IPDI with trifunctional PCLT showed relatively high thermal decomposition temperatures. The hardness and modulus of the UV‐cured poly(urethane acrylate) films, which were measured by a nanoindentation technique, were in the following increasing order: PCLD–IPDI ～ PCLD–TDI < PCLT–IPDI ～ PCLT–TDI. The pencil hardness was 3H for PCLT–IPDI and PCLT–TDI and HB for PCLD–IPDI and PCLD–TDI. Two urethane acrylates prepared from the trifunctional polyol showed better acid and alkali resistances than those made from the bifunctional polyol. These mechanical properties and chemical resistances may have been strongly dependent on the chain flexibility of the molecules and crosslinking density. Regardless of the functionality in the polyol, the change in the yellowness index showed a lower value in the poly(urethane acrylate) coating containing the aliphatic diisocyanate IPDI in comparison with the corresponding poly(urethane acrylate) with the aromatic diisocyanate TDI. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and evaluation of chitosan‐coated polyphosphazene hydrogel beads for drug controlled release

Chitosan‐coated polyphosphazene‐Ca²⁺ hydrogel beads were fabricated by dropping polyphosphazene into CaCl₂/chitosan gelling solution. Polyphosphazene used here was a water‐soluble degradable polyanion (PCPAP), which carried almost two carboxylatophenamino groups on each phosphorus atom of the polymer backbone. Two kinds of turbidimetric titration were applied in this study to reveal the interaction between PCPAP and chitosan within the pH range of 4.57≈7.14. The effect of gelling solution pH on the properties of chitosan‐coated PCPAP beads was especially emphasized. It was found that the PCPAP/chitosan complex prepared at relatively high pH (pH 6.5) dissociated most slowly in pH 7.4 phosphate‐buffered solution (PBS). The erosion of chitosan‐coated beads and the release of model drug (Coomassie brilliant blue and myoglobin) in PBS were both obviously prolonged with the increase of gelling solution pH, exhibiting perfect accordance with the behavior of complex dissociation. In addition, the coating of PCPAP/chitosan complex on the bead surface facilitated the improvement of drug loading efficiency. The higher the gelling solution pH, the more the drug loading efficiency improved. At pH 6.5 (PCPAP 5%, CaCl₂ 7%, chitosan 0.3%), the loading efficiency of myoglobin in beads reached as high as 93.2%. These results indicate that the chitosan‐coated polyphosphazene‐ Ca²⁺ bead is a potential formulation for drug controlled release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1993–1999, 2004     

Preparation and characterization of poly(ethylene glycol) crosslinked chitosan films

Poly(ethylene glycol) (PEG) crosslinked chitosan films with various PEG to chitosan ratio and PEG molecular weight were successfully prepared via the epoxy‐amine reaction between chitosan and PEG‐epoxy. The thermal and mechanical properties and swelling behavior were studied for the PEG crosslinked chitosan films. The mechanical strength of chitosan films were greatly enforced by the introduction of PEG‐epoxy, achieving an elongation of about 80%. It was found that the crosslinked chitosan films form hydrogel in water, achieving a swelling ratio higher than 20 times of original weight. The swelling behavior of chitosan films relied greatly on the molecular weight of the crosslinker PEG‐epoxy and the weight percent of PEG‐epoxy. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Preparation and characterization of hybrid organic–inorganic epoxide‐based films and coatings prepared by the sol–gel process

Hybrid organic–inorganic coatings and free‐standing films were prepared and characterized. The hybrids were prepared from [3‐(glycidyloxy)propyl]trimethoxysilane, diethoxy[3‐(glycidyloxy)propyl]methylsilane, poly(oxypropylene)s of different molecular weights end‐capped with primary amino groups (Jeffamines D230, D400, and T403), and colloidal silica particles with hydrochloric acid as a catalyst for the sol–gel process and water/propan‐2‐ol mixtures as solvents. The structure evolution during the network formation was followed by NMR spectroscopy and small‐angle X‐ray scattering; the surface morphology was tested by atomic force microscopy. The influence of the reaction conditions (the organosilicon precursor, oligomeric amine, ratio of functional groups, and method of preparation) on the network buildup and product properties was studied and examined. The mechanical testing, based on stress–strain experiments, in combination with dynamic mechanical thermal analysis served as an effective instrument for the optimization of the reaction conditions for the preparation of products with desired properties. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 937–950, 2004