Swelling of poly(N-isopropylacrylamide) gels in water-aprotic solvent mixtures

The swelling volume of poly(N-isopropylacrylamide) (PIPAAm) gel in aprotic solvents (acetonitrile (AcN)-, tetrahydrofuran (THF)-, 1,4-dioxane (DO)- and dimethylsulfoxide (DMSO))-water mixtures was measured at 25°C. The gel swollen in water shrank first and then reswelled with addition of the aprotic solvents. At an intermediate mole fraction (XDMSO) range of DMSO-water mixtures, the gel demonstrated a reentrant swelling phenomenon the hydrated gel shrank first on addition of a small amount of solvent, showed a typical wide reentrant transition, and gradually reswelled in the range near pure solvent. On the other hand, the gels in AcN-, THF-, and DO-water mixtures demonstrated a reentrant-convex swelling phenomenon: the gels reswelled after a reentrant phase transition in low Xorg (XAcN, XTHF and XDO), showed a maximum swelling in the intermediate Xorg region, and shrank again gradually in the high Xorg region. Such a swelling behavior of the gel was interpreted by correlating with solution properties of the aqueous aprotic solvent mixtures.The strength of hydrogen bonding around amide groups of the homopolymer was examined in pure solvents (water, THF, and DMSO) and in all proportion of aqueous THF to observe the relation with swelling behavior of gel by spectrum analysis of the amide I and II bands of Fourier Transform Infrared Spectroscopy (FT-IR). The swelling properties of gels in solvents and the aqueous mixtures were well correlated with the peak shifts of amide groups of the homopolymer.     

温敏性PNIPAAm水凝胶对布洛芬的控制释放

采用自由基聚合法在水溶液中制备了温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm),以非水溶性药物布洛芬(IBU)为模型药物分子,研究了该水凝胶的温敏性能及与药物IBU的相互作用,考察了不同温度下(25 ℃和37 ℃)IBU在磷酸盐缓冲溶液(PBS,pH=7.4)中的释放行为.研究结果表明:该水凝胶的最低临界溶解温度(L...     

pH敏感性P(AM-AA-co-C8PhEO10Ac)水凝胶溶胀动力学及其对茶碱的控释

以丙烯酰胺(AM)、丙烯酸(AA)和丙烯酸辛基酚聚氧乙烯醚酯(C8PhEO10Ac)为单体,采用自由基交联共聚法合成了具有pH敏感性的P(AM-AA-co-C8PhEO10Ac)水凝胶.研究了pH、单体配比对凝胶溶胀性能、溶胀动力学和退溶胀动力学的影响.初步探讨了模拟胃液(pH=1.4)、肠液(pH=7.4)中水凝胶对茶碱的控释情况.结果表明:凝胶具有高溶胀、退溶胀速率和良好的pH敏感性等特征;水凝胶的扩散行为在pH=7.4的缓冲溶液中为非Fickian扩散模式;载药凝胶在模拟肠液中对药物的累积释放率明显大于胃液中的累积释放率,其中n(C8PhEO10Ac)∶n(AM)∶n(AA)为1∶20∶30的载药水凝胶对茶碱的累积释放率最大.     

Preparation and characterization of poly(N-isopropylacrylamide)-modified poly(2-hydroxyethyl acrylate) hydrogels by interpenetrating polymer networks for sustained drug release

In order to investigate the influence of hydrophobic moieties formed by poly(N-isopropylacrylamide) (PNIPAm) in a hydrogel matrix on the release behavior of the hydrogel, a series of poly(N-isopropylacrylamide) (PNIPAm)-modified poly(2-hydroxyethyl acrylate-co-2-hydroxyethyl 2-hydroxyethyl methacrylate) (P(HEA-co-HEMA)) via interpenetrating polymer networks (IPNs) were prepared by a sequential UV solution polymerization. Interestingly, it was found that P(HEA-co-HEMA)/PNIPAm IPN indicated a single glass transition temperature (T(g)) and the T(g)s of the IPNs increased with an increase in the PNIPAm component. This phenomenon may be attributed to hydrogen bonding between the two polymer networks, but the hydrogen bonding exerts less influence on the swelling behavior of the IPNs, due to the fact that IPNs can respond to changes in temperature like PNIPAm. Using 2-[(diphenylmethyl)sulphiny]acetamide (modafinil, MOD) and p-hydroxybenzoic acid (HBA) as model drug compounds, the release behavior of the IPNs was studied at body temperature, and it was found that the presence of PNIPAm could retard drug release regardless of the solubility of the drugs. Release profiles of HBA from the IPNs and their component samples as a function of time at 37 degrees C.     

Swelling and deswelling kinetics of poly(N-isopropylacrylamide) gels

Swelling and deswelling kinetics was investigated for three types of cylindrical poly(N-isopropylacrylamide) (PNIPA) gels differing in crosslink density. The temperature dependence curves of the volume of the gel specimens were different from one another. One of the gel specimens was considered as a critical gel showing the continuous volume phase transition. The volume change process of the specimens after a temperature jump was examined. In the deswelling processes with temperature jumps to temperatures higher than 35 degrees C, a phase separation was observed in the gel specimens and the volume change slowed down due to the homogenization after the phase separation. The value of the diffusion constant obtained without the phase separation decreased rapidly as temperature approaches the transition temperature. The rapid decrease for the critical gel indicates the emergence of the critical slowing-down. The value of the critical exponent for the correlation length suggests that the universality class for the volume phase transition of the critical PNIPA gel belongs to the class for the classical theory.     

Swelling kinetics and release characteristic of crosslinked chitosan: Polyether polymer network (semi-IPN) hydrogels

The aqueous swelling kinetics of a series of crosslinked chitosan (cr-CS) with glutaraldehyde (GA) interpenetrating polyether hydrogels have been studied as functions of pH, the N-deacetylation degree of chitosan, the amount of crosslinking agent, the electrolyte composition in solution, temperature, and gel composition. Based on these results, the swelling mechanism of the hydrogels was discussed. The release profiles of chlorhexidini acetas from the semi-IPN were also investigated. © 1994 John Wiley & Sons, Inc.     

Synthesis and characterization of thermo-sensitive poly (N-isopropylacrylamide) hydrogel with fast response rate

Thermo-sensitive poly (N-isopropylacrylamide) (PNIPA) hydrogel with fast response rate was prepared by polymerizing N-isopropylacrylamide (NIPA) in an aqueous hydroxyl-propyl-methyl cellulose solution. The volume phase transition temperature of PNIPA hydrogels was characterized by differential scanning calorimetry (DSC), and the surface morphology was observed by scanning electron microscopy (SEM). The swelling ratios of the hydrogels at different temperatures were measured. Furthermore, the deswelling kinetics of the hydrogels was also studied by measuring their water retention capacity. In comparison with a conventional PNIPA hydrogel prepared in water, the hydrogel synthesized in aqueous hydroxyl-propyl-methyl cellulose solution has higher swelling ratios at temperatures below the lower critical solution temperature and exhibits a much faster response rate to temperature changes. For example, the hydrogel made in aqueous hydroxyl-propyl-methyl cellulose solution lost 89% water within 1 min and about 93% water in 4 min, whereas the conventional hydrogel lost only about 66% water in 15 min from the deswelling measurement in similar conditions. Translated from Chinese Journal of Applied Chemistry, 2006, 23(6): 581–585 (in Chinese)     

Designing Swellable Beads of Alginate and Gelatin for Controlled Release of Pesticide (Cypermethrin)

In the present study biopolymeric beads of sodium alginate and gelatin were prepared by employing CaCl₂ as a crosslinking agent. A series of such microspheres of different compositions were prepared by varying the amounts of sodium alginate, gelatin and CaCl₂ in the feed mixture. The beads were loaded with an insecticide like cypermethrin. The prepared loaded and unloaded beads were characterized by FTIR spectral and Environmental scanning electron microscopy (ESEM) techniques, to gain insight into the molecular structure and morphology of beads, respectively. The swelling experiments were performed for different composition of beads and at varying pH and temperature of the swelling media. The swelling controlled release of insecticide was also investigated for 8 days in bi-distilled water as a release medium. The release experiments were performed under the static and varying experimental conditions and the data obtained were fitted to Fick's equation to evaluate diffusion coefficients of insecticide. The results were further analyzed by Fick's power law equation, and the possible mechanisms of the insecticide release were explored at different experimental conditions. Soil–pot experiments were also performed to demonstrate the applicability of the present controlled release technique to agricultural fields.     

Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow microcapsules

We successfully developed a novel and simple method for preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) hollow microcapsules at the interface of water-in-oil (W/O) single emulsions at a temperature below the lower critical solution temperature (LCST) of PNIPAM. The prepared PNIPAM microcapsules are featured with hollow structures and thin membranes, high monodispersity, excellent reversible thermo-sensitivity and fast response to environmental temperature. This approach exhibits great interests in preparing monodisperse thermo-sensitive microcapsules for encapsulating bioactive materials or drugs requiring mild encapsulation conditions, because of the flexibility in choosing substances being dissolved in the aqueous phase. The preparation methodology demonstrated in this study provides a unique approach for preparing monodisperse hollow polymeric microcapsules with W/O single emulsions.     

Swelling kinetics of poly(N-isopropylacrylamide) minigels

We synthesize poly(N-isopropylacrylamide) (PNIPAM) gels with different sizes in the micrometer scale by a slight variation of a recent emulsion polymerization method (ref 1). The procedure is different than that typically used for obtaining macroscopic PNIPAM hydrogels. The resultant minigel suspension is polydisperse thus allowing the swelling kinetics for different gel sizes to be studied; we do so at temperatures below the volume-transition temperature by wetting with water previously dried particles. The resultant swelling is followed by optical video microscopy. We find that the characteristic swelling time scales with the inverse of the particle dimension squared, in agreement with theoretical predictions (ref 2). The proportionality constant is the network diffusion coefficient D, which for the minigels under consideration appears to be in between that of PNIPAM macrogels and the self-diffusion coefficient of water.     

Preparation of poly(N-isopropylacrylamide) emulsion gels and their drug release behaviors

Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermosensitive DDS dealing with poly(N-isopropylacrylamide) (poly(NIPA)) have been widely studied. Novel NIPA emulsion gels, i.e., NIPA hydrogels containing distributed oil (oleyl alcohol) microdroplets, were synthesized by means of an emulsion-gelation method in which the polymerization of hydrogels in an aqueous phase in an oil-in-water (O/W) emulsion and the loading of a lipophilic drug (indomethacin) dissolved in an oil phase were accomplished simultaneously. The pulsatile (on-off) drug release from the NIPA emulsion gel loading indomethacin to a phosphate buffered saline (PBS) solution was successfully controlled by a temperature swing between 25 degrees C (release off) and 40 degrees C (release on). The mechanism of the pulsatile drug release was discussed in relation to the diffusion rate, distribution ratio, solvent exchange of NIPA hydrogels, and drug release from an NIPA organogel. The mechanism was as follows: the solvent exchange occurred within the NIPA emulsion gel (the NIPA gel-network absorbed oleyl alcohol with indomethacin) at temperatures above the LCST, and the diffusion rate of indomethacin through the solvent-exchanged gel was higher at 40 degrees C than at 25 degrees C.     

Thermoresponsive poly(N-isopropylacrylamide) nanogels/poly(acrylamide) nanostructured hydrogels

Here we report the preparation and characterization of nanostructured thermo-responsive poly(acrylamide) (PAM)-based hydrogels. The addition of slightly crosslinked poly(N-isopropylacrylamide) (PNIPA) nanogels to AM reactive aqueous solution produces nanostructured hydrogels that exhibit a volume phase transition temperature (T_VPT). Their swelling kinetics, T_VPT's and mechanical properties at the equilibrium-swollen state (H_eq) are investigated as a function of the concentration of PNIPA nanogels in the nanostructured hydrogels. Nanostructured hydrogels with PNIPA nanogels/AM mass ratios of 20/80 and above exhibit higher H_eq and longer time to reach the equilibrium swelling than those of the conventional PAM hydrogels. However, the PNIPA nanogels possess thermo-responsive character missing in conventional PAM hydrogels. The T_VPT of nanostructured hydrogels depends on PNIPA nanogel content but their elastic and Young moduli are larger than those of conventional hydrogels at similar swelling ratios. Swelling kinetics, T_VPT, and mechanical properties are explained in terms of the controlled in-homogeneities introduced by the PNIPA nanogels during the polymerization.     

Swelling properties of pH‐responsive hydrophobically modified hydrogels of poly(methacrylic acid‐co‐diallylammonium salt) in aqueous solution

Using diallylmethyl alkyl ammonium salts (CCX) (X is alkyl's chain length, represents 12, 14, 16, and 18, respectively) as a comonomer of methacrylic (MAA), hydrophobically modified hydrogels of poly diallylmethyl alkyl ammonium salts‐methacrylic acid (PCCX‐MAA) were prepared by free radical copolymerization in aqueous solution. The synthetic conditions, such as dosage of cross‐linking agent, reaction concentration and length of alkyl chain were studied in detail. Results indicated that the swelling degree of hydrogels was decreased with dosage of cross‐linking agent, or monomer concentration increased at different pH. Incorporation of the different length of alkyl chain hydrophobic CCX units on PMAA chains by random distribution can change reswelling kinetics. The required time for reaching equilibrium swelling state was longest for PCC16‐MAA. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis, characterization and swelling properties of a chemically cross-linked poly(vinyl alcohol) hydrogel

A poly(vinyl alcohol) hydrogel was prepared by coupling poly(vinyl alcohol) with epichlorohydrin as the cross-linking agent. The structure of the hydrogel was characterized by FTIR and GPC techniques. Various amounts of water were added into the dry gel to swell it, and the quantity of water in various states in the partially swollen hydrogel was determined by DSC technique. The analytical results indicate that the water introduced into the dry gel first combines with the hydrophilic groups of the network chains through hydrogen bond forming non-freezable water. The weight ratio of the non-freezable water to dry gel in the hydrogels is about 0.20. After the non-freezable water is saturated, the additional water penetrates the network space and exists simultaneously both in the freezable and free water states until reaching equilibrium swelling. Translated from Acta Polymeric Sinica, 2006, (5): 671–675 (in Chinese)     

交联聚(N-异丙基丙烯酰胺)/(海藻酸钠/聚(N-异丙基丙烯酰胺))半互穿网络水凝胶的制备及其溶胀性能

将线性聚(N-异丙基丙烯酰胺)(PNIPAAm)和海藻酸钠(SA)分子同时引入到PNIPAAm凝胶中,制备了交联聚(N-异丙基丙烯酰胺)/(海藻酸钠/聚(N-异丙基丙烯酰胺))半互穿网络(Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN)水凝胶。在弱碱性条件下(pH=7.4),改变SA与线性PNIPAAm的质量比对Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN水凝胶的溶胀度没有太大的影响。在酸性条件下(pH=1.0),其溶胀度随着SA与线性PNIPAAm质量比的减小而增大。由于亲水性SA与线性PNIPAAm的协同作用,Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN水凝胶的消溶胀速率得到很大提高。     

羧甲基纤维素与丙烯酸接枝共聚凝胶的溶胀动力学及过溶胀平衡特性的研究

采用接枝共聚合成了羧甲基纤维素钠、丙烯酸与N,N′-亚甲基双丙烯酰胺的交联凝胶, 研究了这类凝胶在不同pH值的缓冲溶液中的溶胀行为, 发现在酸性介质中凝胶的溶胀动力学行为表现出过溶胀平衡特性(overshooting effect), 即凝胶先发生溶胀到最大值, 然后再逐渐消溶胀到平衡. 这种现象可归因于凝胶溶胀过程中羧基之间通过氢键所产生的协同物理交联. 较之凝胶的组成, 缓冲溶液的pH值对过溶胀平衡现象的影响更为显著. 前者是因为凝胶羧基的总摩尔分数并不随两组分结构单元摩尔数的改变而改变, 羧基之间通过氢键形成的物理交联程度在交联剂摩尔分数接近的条件下变化不大; 后者是由于溶液的pH值显著影响凝胶羧基的质子化程度, 进而影响羧基之间通过氢键形成的物理交联程度. 凝胶在酸性介质中的溶胀过程符合E. Díez-Peña等提出的溶胀动力学定量模型, 理论曲线与实验数据有较好的相关性. 凝胶在pH≥5.0的缓冲溶液中的溶胀不产生过溶胀平衡现象, 这一现象归因于完全离子化的羧基之间不能形成物理交联. 凝胶的溶胀过程遵循Schott二级溶胀动力学.     

Effect of network connectivity on the mechanical and transport properties of block copolymer gels

Establishing the independent tunability of transport and mechanical properties in polymer gels would significantly contribute to their implementation as transdermal drug delivery media, among other things. The work conducted herein uses facile changes in the formulation of physically crosslinked styrenic ABA/AB block copolymer organogels to alter their mechanical properties independently from the mass transport of an internally-loaded nanocarrier. Such independent tunability is made possible by altering the relative amounts of ABA triblock and AB diblock copolymers while holding total copolymer concentration fixed. Specifically, three series of gels each with a fixed total copolymer concentration (10, 20, or 30 wt%) comprised of varying triblock copolymer concentration are studied. Small angle x-ray scattering confirms that, at the nanoscale, only gel network connectivity changes within each series, while mechanical and release experiments show that increasing network connectivity leads to significant growth of gel moduli, but little change in nanocarrier release rate.     

明胶-聚异丙基丙烯酰胺水凝胶的溶胀动力学

采用明胶（Gel)和N－异丙基丙烯酰胺（NIPAM）为原料，制备了Gel/聚异丙基丙烯酰胺（PNIPAM）水凝胶系列；研究了原料配比、pH值及温度对水凝胶溶胀速度的影响。结果表明，当温度大于PNIPAM的最低临界溶液温度（LCST）值时，Gel/PNIPAM水凝胶的溶胀速度随着组分中PNIPAM的增加而降低，且溶胀过程以扩散渗透控制为主。而pH对水凝胶溶胀速度的影响与温度有关。Gel/PNIPAM配比为5／5，温度大于LCST时，水凝胶的pH敏感性受明胶控制；温度低于LCST时，pH对水凝胶的溶胀速度的影响很小。     

N-异丙基丙烯酰胺-丙烯酰胺热敏凝胶的溶胀特性

制备并表征了N-异丙基丙烯酰胺-丙烯酰胺热敏凝胶(NIPAm-Am),研究了单体配比、引发剂、交联剂用量和温度对其溶胀特性的影响。结果表明：NIPAm-Am热敏凝胶是由亲水和疏水基团组成的非晶高聚物。mAm／mNIPAm越大,凝胶的平衡溶胀率越大;增加交联剂的用量,凝胶的溶胀率减小,当引发剂的质量分数为0．008时溶胀率达最大值;温度的增加会使凝胶的溶胀率减小,在相转变温度时,溶胀率的变化最大。     

The Cyclodextrins as Modelling Agents of Drug Controlled Release

The controlled release of nicardipine (NC) was achieved by hybridizing its hydrophilic and hydrophobic cyclodextrin (CDs) complexes, i.e., those with hydroxypropyl--cyclodextrin (HPCD) andtriacetyl--cyclodextrin (TACD),respectively. ¹H-nuclearmagnetic resonance (¹H-NMR) was performed to examine the interaction between both CDs and NC in solution. The solid complexes of NC : HPCD and NC : TACD were prepared, in a 1 : 1 molar ratio by the spray-drying method. Complexation in the solid state was demonstrated by differential scanning calorimetry (DSC) and powder X-ray diffractometry. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the USP basket method. The ¹H-NMR studies provided clear evidence of an interaction between the CDs and the aromatic rings of NC. The DSC thermograms of the solid complexes showed no endothermic peak due to NC melting and their diffraction pattern was completely diffuse, which suggested the formation of a novel type solid phase with an amorphous character. The low dissolution rate of NC, a weak basic drug, in alkaline medium was significantly improved by complexation with HPCD. In contrast, the in vitro release of this drug from the NC : TACD complexes was markedly retarded in both dissolution media. An optimal formulation was then designed by the combination, in different molar ratios, of these two complexes. The release behavior of these preparations was investigated and it was observed that the retarding effect was dependent on the amount of the NC : TACD complex. In addition, the initial release rate became faster as the molar ratio of the NC : HPCD complex increased.