紫杉醇PCL-PEG-PCL温敏性缓释凝胶的制备及性能研究

目的 利用聚己内酯-聚乙二醇-聚己内酯(PCL1250-PEG1500-PCL1250)两亲性聚合物温敏凝胶作为载体材料,构建疏水性抗肿瘤药物紫杉醇的载药体系.方法 以辛酸亚锡为催化剂、聚乙二醇为引发剂,引发己内酯单体开环聚合,合成PCL1250-PEG1500-PCL1250三嵌段共聚物.通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行表征:制备不同凝胶浓度及初始载药量的载药温敏凝胶,并对其相转变性能、体外药物释放行为以及体内的生物降解性能进行考察.结果 核磁共振及凝胶渗透色谱测定结果表明:合成的共聚物组成与初始投料比一致,符合设计的PCL1250-PEG1500-PCL1250嵌段聚合物结构;该凝胶在15%～30%浓度区间内,具备温敏性溶胶-凝胶相转变能力;该温敏凝胶对紫杉醇具有可控的药物缓释能力,通过改变凝胶浓度及初始载药量可调节药物释放速率和维持释放的时间.小鼠背部皮下注射PCL1250-PEG1500-PCL1250溶胶后在体内迅速原位凝胶化,凝胶随植入时间逐渐降解至45 d时基本降解完全.结论 PCL1250-PEG1500-PCL1250温敏凝胶作为紫杉醇载药体系具有良好的药物控释能力和体内生物降解性能.     

紫杉醇PCL—PEG—PCL温敏性缓释凝胶的制备及性能研究

目的利用聚己内酯-聚乙二醇-聚己内酯（PCL1250-PEG1500-PCL1250）两亲性聚合物温敏凝胶作为载体材料,构建疏水性抗肿瘤药物紫杉醇的载药体系。方法以辛酸亚锡为催化剂、聚乙二醇为引发剂,引发己内酯单体开环聚合,合成PCL1250-PEG1500-PCL1250三嵌段共聚物。通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行表征;制备不同凝胶浓度及初始载药量的载药温敏凝胶,并对其相转变性能、体外药物释放行为以及体内的生物降解性能进行考察。结果核磁共振及凝胶渗透色谱测定结果表明：合成的共聚物组成与初始投料比一致,符合设计的PCL1250-PEG1500-PCL1250嵌段聚合物结构;该凝胶在15％～30％浓度区间内,具备温敏性溶胶-凝胶相转变能力;该温敏凝胶对紫杉醇具有可控的药物缓释能力,通过改变凝胶浓度及初始载药量可凋节药物释放速率和维持释放的时间。小鼠背部皮下注射PCL1250-PEG1500-PCL1250溶胶后在体内迅速原位凝胶化,凝胶随植入时间逐渐降解至45d时基本降解完全。结论PCL1250-PEG1500-PCL1250温敏凝胶作为紫杉醇载药体系具有良好的药物控释能力和体内生物降解性能。     

超声引发抗肿瘤药物定时定量释放

研究超声对于高分子聚合物Pluronic P-105载药缓释系统的影响作用.方法 配制不同浓度的P-105溶液,研究P-105溶胶-凝胶转化点及其影响因素.构建P-105载米托蒽醌水凝胶系统,将水凝胶暴露于不同频率与功率的超声波作用下,一定时间后,用PBS缓冲液冲洗水凝胶,根据缓冲液中米托蒽醌的紫外吸光值计算得出超声引发的药物的释放量.结果 P-105的溶胶-凝胶转化点受P-105的浓度及外界环境温度的影响.在浓度低于26%的区域或较低温度时没有凝胶形成,浓度高于26%或者温度接近人体正常体温(或高于体温)时即为凝胶.P-105载药系统中药物的释放量与超声波的频率与功率有关,释放量随着超声功率增加而增加,随频率增加而降低.结论 超声可以引发高分子聚合物Pluronic P-105载药系统的药物定时定量释放.     

载银水凝胶或载抗生素壳聚糖水凝胶在抑菌性能和细胞毒性方面的研究

目的研究壳聚糖水凝胶,壳聚糖载银水凝胶和壳聚糖载抗生素水凝胶短期的抑菌功效和细胞毒性。方法通过添加交联剂后制备壳聚糖水凝胶,并有效装载银离子或硫酸庆大霉素。进行抑菌实验和累计释放实验了解壳聚糖基水凝胶的抗菌性能和药物控释性。通过使用材料的浸提液检测这三种水凝胶的细胞毒性。结果抑菌实验结果表明壳聚糖水凝胶,壳聚糖载银水凝胶和壳聚糖载抗生素水凝胶均能有效抑制金黄色葡萄球菌的增殖。且壳聚糖载抗生素水凝胶具有最佳的抑菌性能且极大地抑制了生物膜的形成。体外药物释放显示抗生素在7天内的累计释放多于60%;而银离子的释放低于10%。细胞毒性实验表明这三个凝胶材料无明显细胞毒性。结论壳聚糖基水凝胶具有良好的短期抑菌效果,可降解,且无明显细胞毒性,在骨科应用方面有着巨大的前景。     

一种新型可降解缓释微系统的优化设计

多腔体的微型可降解高分子聚合物药物缓释系统是一种新型给药技术,其载体结构是利用MEMS工艺的制备特点,结合药物释放的要求和高分子聚合物生物降解特性进行设计的.为了达到该系统在体内长期释药的性能,对释药载体的结构进行参数优化十分必要.文中建立了具有多腔体的微型可降解高分子聚合物给药载体的释药模型以及载体的结构优化模型,仿真及优化结果表明该模型可以用来指导基于可降解材料的结构优化设计.     

壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶的体外抗结核作用

文题释义：基质细胞衍生因子1：是一种参与免疫细胞活化、分化和迁移及伤口愈合、角膜上皮再生和组织修复等过程的趋化因子,能促进干细胞的生长和发育,参与调节成骨分化,可通过细胞归巢提高干细胞向病灶区的趋化作用。而基质细胞衍生因子1的失活会损害成骨细胞的发育和分化。此外,其还与血管生成密切相关。 异烟肼：具有较高的杀菌活性,是治疗结核病的一线药物。世卫组织建议将异烟肼作为结核病的标准疗法,用于潜伏性结核病感染者的预防治疗,与利福平、吡嗪酰胺和乙胺丁醇一起用于治疗活动性肺结核。异烟肼的活化形式与脂肪酸生物合成Ⅱ型系统中的NADH依赖型烯醇酰基载体蛋白还原酶异烟肼a结合,阻断细菌细胞壁关键成分支原体酸的合成。 背景：抗结核化疗是目前治疗骨关节结核的主要手段,然而全身给药难以维持病灶区的有效浓度,治疗效果欠佳。 目的：制备一种原位、长期释放抗结核药物且兼备促成骨作用的壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶。 方法：将亲水性的抗结核药物异烟肼和疏水性的基质细胞衍生因子通过复乳法负载到聚乳酸-羟基乙酸中,制备聚乳酸-羟基乙酸载药微球,共混至壳聚糖-明胶水凝胶支架中,制备壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶。检测聚乳酸-羟基乙酸载药微球、壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶的体外释药与抗结核杆菌的能力。将成骨前体细胞MC3T3-E1分别接种于载药微球与联合载药水凝胶表面,CCK-8法检测细胞活力,碱性磷酸酶活性检测细胞的成骨性能。 结果与结论：①载药微球中异烟肼1 h内的突释约为23.3%,2 d内的释放率约为42.6%,随后进入缓释期,25 d后进入平台期;基质细胞衍生因子1在1 h内的累积释放率约为19.8%,2 d内的释放率约为44.7%,随后进入缓释期,25 d后进入平台期;联合载药水凝胶中异烟肼和基质细胞衍生因子1最初1 h的释放分别为8.3%和8.5%,第2天的累计释放率分别为15.2%和17.6%,远低于聚乳酸-羟基乙酸微球;②体外4周后,联合载药水凝胶的抑菌直径大于载药微球,抑菌率高于载药微球(P < 0.05);③联合载药水凝胶与载药微球均具有良好的细胞相容性,细胞活力均约为100%;④培养5,10 d后,联合载药水凝胶表面的细胞碱性磷酸酶活性与载药微球比较差异无显著性意义(P > 0.05);⑤结果表明,原位壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶有作为治疗骨关节结核及其他骨关节感染的潜力。 ORCID: 0000-0003-4166-2492(张贺龙) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

微透析和高效液相色谱检测万古霉素在清醒兔眼玻璃体内的浓度

背景：万古霉素玻璃体内注射后的药代动力学资料较少。 目的：观察万古霉素玻璃体腔内注射后在清醒兔眼玻璃体内的浓度。 方法：将微透析探针植入清醒正常兔眼和细菌性眼内炎兔眼玻璃体内24 h后,向玻璃体内注射10 g/L万古霉素0.1 mL,利用微透析采样技术联合高效液相色谱法连续检测万古霉素注射后0.5,1,2,4,6,12,24,48,72,84 h,兔眼玻璃体内的药物浓度。 结果与结论：万古霉素在正常兔眼玻璃体内的代谢呈开放式二室模型,玻璃体内的峰值浓度为695.92 mg/L,半衰期51.66 h;在细菌性眼内炎兔眼玻璃体内的代谢呈一室模型,万古霉素的峰值浓度为713.35 mg/L,半衰期为11.91 h。所有动物给药84 h,玻璃体内万古霉素的浓度均高于最小抑菌浓度。实验在动物清醒状态下实时、连续、动态采样,检测结果准确,能满足万古霉素药动学分析的需要。     

对映异构聚乳酸/聚乙二醇空间异构复合水凝胶的药物释放及形貌和细胞毒性

背景：目前生物降解水凝胶已被广泛应用于抗癌药物及生物活性大分子的装载,但为了保护生物活性大分子的活性,需要得到凝胶化条件更温和,凝胶化时间更短的凝胶体系。 目的：制备对映异构聚乳酸∕聚乙二醇的空间异构复合水凝胶,使其具有更短的凝胶化时间,实现对模拟药物溶菌酶的装载和控释。 方法：以聚乙二醇为引发剂,辛酸亚锡为催化剂,丙交酯与聚乙二醇发生开环聚合反应,得到聚乳酸/聚乙二醇的三嵌段共聚物(PLLA-PEG-PLLA 和 PDLA-PEG-PDLA)。用1H NMR,FT-IR 和 XRD表征三嵌段共聚物。10% PLLA20-PEG227-PLLA20的水溶液和10%PDLA21-PEG227-PDLA21的水溶液在室温下混合,12 h后形成凝胶。通过XRD考察凝胶化机制,以溶菌酶为模拟药物,考察凝胶的释药特性,通过扫描电镜考察凝胶的形貌,采用MTT法考察凝胶的细胞毒性。 结果与结论：成功得到聚乳酸/聚乙二醇的三嵌段共聚物,在嵌段共聚物中,聚乳酸嵌段和聚乙二醇嵌段都能结晶,但以聚乙二醇嵌段的结晶为主。通过XRD证明凝胶中存在空间异构复合作用,溶菌酶在凝胶中通过凝胶的溶蚀和降解行为,在7 d之内释放完全。通过扫描电镜观察到冻干的水凝胶呈三维贯穿的多孔结构,空隙尺寸在50~100 μm 之间。鼠成纤维细胞与浓度为100%的凝胶浸提液共培养72 h之后,细胞的存活率为99.3%。     

聚乳酸/聚乙二醇琥珀酸酯-姜黄素纳米粒的制备及体外评价*

背景：聚乳酸及其共聚物是一类具有良好生物相容性的可降解高分子材料,已被广泛用于可生物降解型药物缓释或靶向给药系统中。 目的：探索载药纳米粒制备条件对包封率和载药量的影响,确定最佳制备工艺条件。 方法：以维生素E1000聚乙二醇琥珀酸酯(TPGS)为乳化剂、姜黄素为模型药物、聚乳酸为载体材料,采用O/W型乳化-溶剂挥发法制备聚乳酸-姜黄素纳米粒,以包封率和载药量为主要指标,单因素实验探索影响两指标的主要因素,再正交试验设计优化制备工艺。 结果与结论：通过正交试验设计制备聚乳酸-姜黄素纳米粒的最佳工艺为：水油相比10∶1,聚合物浓度15 g/L,药物浓度3 g/L,乳化剂TPGS浓度0.03%。以此工艺制备的载药纳米粒外形圆整光滑,粒度分布较为均匀,平均粒径为167.5 nm,包封率为89.52%,载药量为13.72%,纳米粒前期突释不明显具有良好的缓释作用。该工艺稳定、简单可行,优化制备工艺得到的聚乳酸-姜黄素纳米粒粒径适中、包封率和载药量较高。     

加替沙星-聚癸二酸酐局部缓释系统的体内释药特性CSCD

背景:全身大剂量应用抗生素治疗骨感染的不良反应较多,效果不是十分理想,因此探索一种以可降解材料为载体预防骨感染的方法具有很好的应用价值。目的:分析加替沙星-聚癸二酸酐局部缓释系统的体内释药特性。方法:在新西兰大耳白兔右侧膝关节制作3mm×6mm大小的骨窗,植入加替沙星-聚癸二酸酐缓释制剂,术后1,2,3,6,9,12,15,18,25,30d取心脏血、骨组织及骨髓组织标本,以高效液相色谱法测定各组织内加替沙星浓度;扫描电镜观察加替沙星-聚癸二酸酐缓释制剂植入前后的结构变化。结果与结论:加替沙星-聚癸二酸酐缓释制剂植入后,骨髓组织内药物浓度逐渐降低,在第1天出现了一个较高的高峰,第3-15天药棒释放较平稳,15-30d逐渐降低,但在30d末时的药物浓度仍大于对金黄色葡萄球菌的最小抑菌浓度0.1mg/L;骨组织内的药物浓度高峰出现于第3天,其余时间的浓度较平稳,并且均大于0.1mg/L;在同一时间点,血标本中药物浓度小于骨髓组织和骨组织内药物浓度。加替沙星-聚癸二酸酐缓释制剂是表面溶蚀降解,降解残留物为小球状,其内部结构未发生变化,在药物持续释放过程中药棒未发生崩解和碎片化。表明加替沙星-聚癸二酸酐局部缓释制剂具有良好的载药及药物缓释能力。     

Hydrogel probe for iontophoresis drug delivery to the eye

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm² for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. Iontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.     

Hydrogel probe for iontophoresis drug delivery to the eye

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm2 for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. lontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.     

Biodegradable dextran-polylactide hydrogel network and its controlled release of albumin

The objective of this paper was to study the release of bovine serum albumin (BSA) from a series of biodegradable hydrogels having a wide range of hydrophilicity to hydrophobicity, swelling, and biodegradation properties. BSA was incorporated into a series of biodegradable hydrogels made from a dextran derivative of allyl isocyanate (dex-AI, as the hydrophilic constituent) and poly(DL-lactic acid) diacrylate macromer (PDLLAM, as the hydrophobic constituent). The release kinetics of BSA from these dex-AI/PDLLAM hydrogels was studied. Laser confocal scanning microscopy was used to investigate the morphological change of the hydrogels, as well as BSA distribution in the hydrogels, as a function of dex-AI to PDLLAM composition ratio and incubation time. We found that the incorporation of PDLLAM into dex-AI reduced the initial burst release of BSA due to its more homogeneous distribution in the hydrogels. As the PDLLAM component increased, the rate of formation of a loose three-dimensional (3D) network structure increased; consequently, the sustained rate and extent of BSA release increased. Both release index and diffusion coefficient (from release kinetics data) increased as the PDLLAM component increased in the hydrogels. The data suggest that the release of BSA was controlled by both diffusion of BSA through swelling of the hydrophilic phase during an early stage, and degradation of the hydrophobic phase during a late stage, and also that the magnitude of diffusion versus degradation controlled release is dependent on composition ratio and immersion time.     

Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and controlled drug release

The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.     

About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study

The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate-based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. pHEMA-UV revealed some superficial porosity and a lower short-range order than pHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMA-UV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered.     

Controlled release of drugs from multi-component biomaterials

In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report on a multi-component drug delivery biomaterial that consists of a hydrogel matrix in which drug-loaded biodegradable microcarriers are dispersed, and whose potential applications could be found in the design of implantable devices with long-term activity, as required by contraceptive and hormone replacement treatments. The release profile of the drug can actually be tuned by the complex interplay of several release mechanisms, including the permeability and eventually the degradation rate of the microcarriers and the diffusion through the hydrogel. The hydrogel consisted of 2-hydroxyethyl methacrylate cross-linked by ethylene glycol dimethacrylate. The microcarriers were biodegradable poly-epsilon-caprolactone (PCL) microspheres in which active molecules, such as levonorgestrel (LNG), were encapsulated. The hydrogels were characterized by water swelling, thermal properties, LNG diffusion through drug-free and drug-depleted hydrogel membranes and LNG release from devices with drug dispersed in the hydrogel. The PCL microspheres were observed by scanning electron microscopy; their size distribution, LNG loading and release were also investigated. The hydrogel-microsphere assemblies were characterized in terms of the distribution of the microspheres within the hydrogel, water swelling and the release of the encapsulated molecules. The developed device, due to its composite structure, has the ability to combine several release mechanisms, leading to drug release obeying zero-order kinetics for most of the time.     

Injectable in situ dual-crosslinking hyaluronic acid and sodium alginate based hydrogels for drug release

A series of injectable in situ dual-crosslinking hydrogels (HA/ALG) based on oxidized sodium alginate (oxi-ALG) and hyaluronic acid modified with thiol and hydrazide (HA-SH/CDH) were prepared via hydrazone bonds and disulfide bonds. The chemical structures, morphologies, rheological properties, gelling time, swelling ratio, degradation rate and drug release behavior of hydrogels were investigated. HA/ALG hydrogels exhibited tunable gelling time, rheological properties, swelling ratio and degradation rate with varying precursor concentrations. The gelling time of HA/ALG hydrogels ranged from 157?s to 955?s, the values of yield stress of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were 1724, 4349 and 5306?Pa, and the degradation percentage of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were about 64%, 51% and 42% after incubating 35?days, respectively. Bovine serum albumin (BSA) was used as a model drug to investigate the drug controlled release properties, and the in vitro cumulative release percentage of BSA from HA2/ALG2, HA3/ALG3 and HA4/ALG4 drug-loaded hydrogels were about 79%, 72% and 69% after 20?days. The series of injectable in situ dual-crosslinking HA/ALG hydrogels could be an attractive candidate for drug delivery system, tissue engineering and regenerative medicine.     

In vitro release behavior of insulin from biodegradable hybrid hydrogel networks of polysaccharide and synthetic biodegradable polyester

The controlled release of insulin from a series of biodegradable hybrid hydrogel network containing dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of composition ratio was investigated. Laser confocal scanning microscope was used to understand the insulin dispersion and release mechanism in the hydrogels. We found that the dispersion of insulin in the hydrogel network appeared to become less homogeneous as the PDLLAM composition in the hydrogel increased. The increase in hydrogel degradability imparted by PDLLAM incorporation shifted the hydrogel to a more open structure at a later release time, which facilitated the release rate and extent of insulin. From the result of release kinetics study (i.e., diffusion coefficient), insulin release occurred through diffusion and degradation controlled mechanisms. In addition, a comparison of the release characteristics of indomethacin, insulin and bovine serum albumin from the hydrogel network showed that the following parameters determined the release kinetics: drug molecular weight and size, hydrogel swellability and degradability, drug solubility in water and the hydrophobic interaction between drugs and the hydrogel network.     

Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis,characterization, and preliminary release studies of protein drugs

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.     

Polymeric matrices based on graft copolymers of PCL onto acrylic backbones for releasing antitumoral drugs

Graft copolymers of poly(epsilon-caprolactone) (PCL) on poly(dimethylacrylamide) (PDMAm), poly(methylmethacrylate) (PMMA), or on copolymers of poly(DMAm-co-MMA) have been synthesized and characterized by (1)H NMR spectroscopy, differential scanning calorimetry (DSC), and size exclusion chromatography (SEC). These partially biodegradable copolymer matrices have been proposed as drug delivery systems for the release of low-molecular-weight glycosides. Octyl-N-acetyl-6-O-[2,2-bis(hydroxymethyl)-3-hydroxypropyl]-alpha-D-glucosamide, a synthetic carbohydrate able to inhibit the proliferation of human malignant glioma cells in culture and transplanted glioma in rats was selected as drug model. The in vitro aqueous behavior of four drug-loaded and unloaded graft copolymers of different MMA: DMAm and PCL ratios has been analyzed performing swelling, degradation, and drug release experiments. An intimate dependence of the aqueous behavior with the composition has been found. The higher was the DMAm content, the higher was the hydrophilicity of the synthesized systems as well as the swelling, degradation, and drug release rate. In vivo experiments in pigs demonstrated the very good tolerance of drug-loaded implanted polymeric discs, and that >95% of the charged drug is released after 2 months' implantation.