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1.
In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (Mc), polymer volume fraction in swollen state (V2s), number of repeating units between crosslinks (Mr) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.  相似文献   

2.
In this work, poly (vinyl alcohol) (PVA) hydrogels with different degree of hydrolysis (DH) were prepared by chemical crosslinking with glutaraldehyde (GA). The nanostructure of the resulting hydrogels was investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Synchrotron small-angle X-ray scattering characterization (SAXS). In vitro tests were performed by swelling ratio assays in different pH solutions. The infrared spectra of the crosslinked PVA showed absorption bands of the acetal bridges resulted from the reaction of the GA with the OH groups from PVA. Also the FTIR spectroscopy was used to determine the crystallinity of the PVA film based on the relative intensity of the vibration band at 1141 cm 1. The results have showed an increase of hydrogel crystallinity with higher DH of PVA. SAXS patterns have clearly indicated important modifications on the PVA semicrystalline structure when it was crosslinked by GA. The swelling ratio was significantly reduced by chemically crosslinking the PVA network. PVA-derived hydrogel with chemically modified network was found to be pH-sensitive, indicating a high potential to be used in drug delivery polymer system.  相似文献   

3.
Current research work was conducted to synthesize Thiol modified arabinoxylan and its application in fabrication of hydrogel. Thioglycolic acid was esterified with arabinoxylan to prepare Thiolatedarabinoxylan. Appearance of peak at 2533.34?cm?1 in FTIR and thiol content showed successful thiolation. The pH-dependent Thiolatedarabinoxylan/acrylic acid (TAX/AA) hydrogels of perindopril erbumine were prepared via free-radical co-polymerization. Perindopril erbumine (PE) was employed as model drug. Different batches with different feed ratio of TAX, AA, and MBA were prepared and their influence on swelling, solvent penetration, and consequent drug release was investigated. Swelling coefficients increased with increase in pH. TAX/AA hydrogels were characterized by Fourier-transform infrared spectroscopy (FT-IR), Thermal Analysis (TA), X-Ray diffraction (XRD), and scanning electron microscope (SEM). Dissolution studies were performed at pH 1.2 and 7.4 in which drug release showed direct correlation with TAX and AA ratio. In vivo studies showed that Cmax of TAX-co-AA based hydrogel was 81.57?±?0.35?ng/ml which was maintained for a longer time after its administration. All the results of in vivo studies were significant and TAX-co-AA based hydrogel enhances the bioavailability of perindopril erbumine.  相似文献   

4.
Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).  相似文献   

5.
Hydrogels forming in-situ have gained great attention in the area of bone tissue engineering recently, they were also showed to be a good and less invasive alternative to surgically applied ones. The primal focus of this study was to prepare chitosan-glycerol phosphate thermosensitive hydrogel formed in-situ and loaded with risedronate (bone resorption inhibitor) in an easy way with no requirement of complicated processes or large number of equipment. Then we investigated its effectiveness for bone regeneration. In-situ forming hydrogels were prepared using chitosan cross-linked with glycerol phosphate and loaded with risedronate and nano-hydroxyapatite as bone cement. The prepared hydrogels were characterized by analyzing their gelation time at 37?°C, % porosity, swelling index, in-vitro degradation, rheological properties, and in-vitro drug release. Results showed that the in-situ hydrogels prepared using 2.5% (w/v) chitosan cross-linked with 50% (w/v) glycerol phosphate in the ratio (9:1, v/v) reinforced with 20?mg/mL and nano-hydroxyapatite possessed the most sustained drug release profile. This optimized formulation was further evaluated using DSC and FTIR studies, in addition to their morphological properties using scanning electron microscopy. The effect on Saos-2 cell line viability was evaluated also using MTT assay on the optimized hydrogel formulation in addition to their action on cell proliferation using fluorescence microscope. Moreover, calcium deposition on the hydrogel and alkaline phosphatase activity were evaluated. Risedronate-nano-hydroxyapatite loaded hydrogels significantly enhanced the Saos-2 cell proliferation in addition to enhanced alkaline phosphatase activity and calcium deposition. Such results suggest that risedronate-nano-hydroxyapatite loaded hydrogels present great biocompatibility for bone regeneration. Proliferation of cells, as well as deposition of mineral on the hydrogel, was an evidence of the biocompatible nature of the hydrogel. This hydrogel formed in-situ present a good less invasive alternative for bone tissue engineering.  相似文献   

6.
One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48?h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.  相似文献   

7.
用零长度的1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC·HCl)和N-羟基丁二酰亚胺(NHS)作为偶联剂和稳定剂制备了壳聚糖基透明质酸复合水凝胶,探讨了溶液pH值对该类水凝胶溶胀性的影响。溶液的pH在4.0时,该类水凝胶的溶胀率最低,升高和降低溶液的pH,该类水凝胶的溶胀率均升高,文中还对水凝胶的降解率进行了研究,实验发现,交联后的水凝胶具有一定的稳定性。包埋在此水凝胶中的牛血清蛋白(BSA)释放随载药介质pH值的变化而显著不同,pH 7.4条件下载药的水凝胶释药率大于pH 1.2条件下的释药率。因此,具有pH敏感性的壳聚糖透明质酸复合水凝胶在药物运输领域具有潜在的应用。  相似文献   

8.
The purpose of this study was to prepare hydrogels and microemulsion (ME)-based gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to evaluate the use of these formulations for the antifungal treatment of fungal infections. Three different hydrogel formulations were prepared using chitosan, Carbopol® 974 and Natrosol® 250 polymers. A pseudo-ternary phase diagram was constructed, and starting from ME formulation, a ME gel form containing 1% Carbopol 974 was prepared. We also examined the characteristic properties of the prepared hyrogels. The physical stability of hydrogels and the ME -based gels were evaluated after storage at different temperatures for a period of 3 months. The release of TER-HCL from the gels and the commercial product (Lamisil®) was carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at 32?°C. The results of the in vitro release study showed that the Natrosol gel released the highest amount of drug, followed by Carbopol gel, chitosan gel, commercial product, and the microoemulsion-based gel in that order. In vitro examination of antifungal activity revealed that all the prepared and commercial products were effective against Candida parapsilosis, Penicillium, Aspergillus niger and Microsporum. These results indicate that the Natrosol®-based hydrogel is a good candidate for the topical delivery of TER-HCL.  相似文献   

9.
Attempting to prepare a convenient bioavailable formulation of vitamin B12 (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B12 bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone® I.M. injection.  相似文献   

10.
Hydrogels are extensively studied as carrier matrices for the controlled release of bioactive molecules. The aim of this study was to design gelatin-based hydrogels crosslinked with genipin and study the impact of crosslinking temperature (5, 15 or 25°C) on gel strength, microstructure, cytocompatibility, swelling and drug release. Gels crosslinked at 25°C exhibited the highest Flory–Rehner crosslink density, lowest swelling ratio and the slowest release of indomethacin (Idn, model anti-inflammatory drug). Diffusional exponents (n) indicated non-Fickian swelling kinetics while drug transport was anomalous. Hydrogel biocompatibility, in vitro cell viability, cell cycle experiments with AH-927 and HaCaT cell lines indicated normal cell proliferation without any effect on cell cycle. Overall, these results substantiated the use of genipin-crosslinked hydrogels as a viable carrier matrix for drug release applications.  相似文献   

11.
Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).  相似文献   

12.
To take advantage of the drug-binding ability of albumin as a component of drug delivery system, we have prepared hydrogels consisting of alginic acid (AL) and recombinant human serum albumin (rHSA) by dehydrating condensation using N-hydroxysuccininimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. As rHSA content increased, the swelling ratio of the hydrogel decreased, indicating rHSA functioned as a crosslinker. In fact, trypsin treatment solubilized the hydrogel. Salicylic acid, which has high affinity for rHSA, was loaded most on the hydrogel of the highest rHSA content despite the lowest swelling ratio. Meanwhile, drugs with less affinity for HSA such as o-anisic acid and benzoic acid were preferably loaded on the hydrogel having the highest swelling ratio but the lowest HSA content. The release of salicylic acid from the hydrogel sustained longer than o-anisic acid and benzoic acid, reflecting the affinity of the drug for HSA. Furthermore, the hydrogel could carry much of positively charged dibucaine by the interaction with anionic alginic acid and showed highly sustained release. Since the safety of AL and rHSA in medical use is guaranteed, rHSA-crosslinked AL hydrogel is expected to use as a sustained drug release carrier for drugs having affinity for HSA and those with cationic charge.  相似文献   

13.
Context: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. Objective: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. Methods: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez® 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. Results and Discussion: Nanocapsules showed mean particle size and zeta potential of 201 ± 6 and ?5.73 ± 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 ± 2.96 mg/cm2/h1/2) compared to the hydrogels containing the free drug (k = 26.65 ± 2.09 mg/cm2/h1/2). Conclusion: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.  相似文献   

14.
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.  相似文献   

15.
In this work, a pH/temperature responsive hydrogel (PMEA) from N-acryloylglycine methyl ester (NAGME), N-acryloylglycine ethyl ester (NAGEE), and acrylic acid (AAc) was synthesized by free radical polymerization. The swelling behaviors and drug release properties of hydrogels were systematically investigated at different temperature, pH, and AAc content. It was found that the hydrogel PMEA demonstrated pH and temperature responsive nature. The caffeine-release behaviors showed that only 49.1% caffeine was released from PMEA in pH 2.70 phosphate buffer solution (PBS) after 500 minutes, whereas more than 93.9% caffeine was gradually diffused into the medium in pH 7.49 PBS over the same time interval. In addition, the caffeine release was much higher at 37°C than that at 14°C in deionized water. As seen from the results, the PMEA seems to be a potential drug carrier with pH-temperature responsiveness.  相似文献   

16.
In this work, the carboxymethyl chitosan (CMCTS) grafted poly(N‐vinylpyrrolidone) (PVP) copolymers were synthesized. The hydrogel beads containing VB2 were prepared from the copolymers by an ionic crosslinked. The experimental results shown that VB2 drug release rate from those beads decreased with the increasing grafting percentage, crosslinker concentration and pH value of the medium. Besides, the beads have the better control ability for releasing of model drug than CMCTS does.  相似文献   

17.
Poly (vinyl alcohol) hydrogels containing different concentrations of chitosan with molecular weight of 471 and 101 kDa were crosslinked by gamma irradiation at a dose of 25 kGy. The swelling behavior, gel content and morphological structure of the blend were investigated. The antibacterial effect, as a function of chitosan content and molecular weight in the hydrogel, was investigated against Escherichia coli and Bacillus subtilis. With increasing chitosan content the equilibrium degree of swelling of the blend increased and the gel fraction decreased. Results of antibacterial activity of chitosan revealed that chitosan was more effective in inhibiting growth of gram positive bacteria than that of gram negative ones. It was observed that, the chitosan content as well as its molecular weight has a direct influence on bacteria growth inhibition. The higher the chitosan content in the blend and the higher its initial molecular weight, the larger was the inhibition zone diameter. The bacteria growth inhibition was attributed to the diffusion of entrapped chitosan from the hydrogel blend to the culture medium.  相似文献   

18.
Biodegradable polymers are compatible, permeable and nontoxic, thus they can provide a useful tool for drug delivery or tissue engineering. These polymers can form hydrogels, which are suitable vehicles for different types of materials e.g. drugs, bioactive molecules or cells. In the case of dentistry, photopolymerization is an obvious method to obtain in situ useable devices which can provide a more efficient way of tailoring drug release. A hydrogel system was developed based on poly-gamma-glutamic acid that was modified with methacryloyl groups to achieve this purpose. The resulting new reactive structure was proved by NMR spectroscopy. The swelling ratio of this type of hydrogel has been found remarkable, over 300 % after 24 h, and it can release 5 ng/mm2 metronidazole. The prepared hydrogels were nontoxic as viability, cytotoxicity tests and cell morphology investigations proved it. These results render this model system an excellent candidate for use as an in situ curing local drug delivery device. The new photoactive system can be utilized in the treatment of periodontal diseases or raising the effectiveness of drugs used only in the minimal effective dose.  相似文献   

19.
Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m2/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.  相似文献   

20.
A kind of novel three-dimensional crosslinked hydrogel was synthesized via Michael-type addition reaction of dithiothreitol (DTT) as a crosslinker/extender towards the self-assembly of α-cyclodextrins (α-CDs) with acryloyl end capped 3-arm PEG. The supramolecular structure of the resulting hydrogels was characterized by using FT-IR, TGA, XRD and DSC measurements. The effect of varying the amount of α-CDs was studied on the crosslinking process. Interestingly, this conjugation reaction is smoothly carried out at physiological temperature and pH in the absence of any sensitizer or catalyst. It appears that these chemically crosslinked hydrogels have the potential to be used as carriers for drug controlled release and scaffolds for injectable tissue engineering.  相似文献   

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