Engineering design and molecular dynamics of mucoadhesive drug delivery systems as targeting agents

The goal of this critical review is to provide a critical analysis of the chain dynamics responsible for the action of micro- and nanoparticles of mucoadhesive biomaterials. The objective of using bioadhesive controlled drug delivery devices is to prolong their residence at a specific site of delivery, thus enhancing the drug absorption process. These mucoadhesive devices can protect the drug during the absorption process in addition to protecting it on its route to the delivery site. The major emphasis of recent research on mucoadhesive biomaterials has been on the use of adhesion promoters, which would enhance the adhesion between synthetic polymers and mucus. The use of adhesion promoters such as linear or tethered polymer chains is a natural result of the diffusional characteristics of adhesion. Mucoadhesion depends largely on the structure of the synthetic polymer gels used in controlled release applications.     

Gentamicin release from photopolymerized PEG diacrylate and pHEMA hydrogel discs and their in vitro antimicrobial activities

Hydrogels based on poly(ethylene glycol)-diacrylate (PEG-DA) and 2-hydroxyethyl methacrylate (HEMA) were polymerized with cross-linking agent ethylene glycol diacrylate (EGDMA) under mild photoinitiating conditions. PEG-DA and HEMA concentrations of disks with 1 ± 0.3 mm thickness were 30% and 50% w/w and 40% and 60% w/w, respectively. Gentamicin sulphate was incorporated into the hydrogel during photopolymerization and its release kinetics were tested by spectrophotometric method at 255 nm wavelength in phosphate buffer (pH 7.4) and citrate buffer (pH 2.2). The drug release in citrate buffer was faster compared with to phosphate buffer. The release of drug from 40% HEMA containing hydrogel showed Fickian diffusion mechanisms in phosphate buffer (pH 7.4). Antimicrobial efficiency of the samples was tested by agar diffusion method in two different bacterial cultures (Pseudomonas aeruginosa [ATCC 10145], Staphylococcus aureus [ATCC 25923]). Inhibition zone diameter (mm) surrounding each sample was measured after 24 hr incubation of drug loaded disks onto agar plates at 37°C. Inhibition zone formation also confirms that gentamicin sulphate preserves its antimicrobial activity after subjected to photopolymerization conditions.     

Polysaccharides for Colon Targeted Drug Delivery

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.     

Patent Briefing

The present work is focused on investigating the controlled drug release behavior of Poly [N-isopropylacrylamide-co-2-Hydroxyethylacrylate] (P [NIPAm-HEAc])-based hydrogel. The synthesis process includes the preparation of monodispersed hydrogel nanoparticles containing specific functional groups, followed by cross-linking to neighboring spheres to stabilize the entire network. The color and volume of these crystalline hydrogel networks can reversibly change in response to external stimuli such as temperature, pH, and other environmental conditions. The feasibility of the hydrogel as a controlled release vehicle for 5-fluorouracil is evaluated.     

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam

Abstract

Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX).

Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application.

Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430?nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of ?19.1 to ?25.7?mV. The release profiles of all formulations exhibited sustained release characteristics over 48?h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel.

Conclusion: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.     

Mechanical properties and thermal behaviour of PEGDMA hydrogels for potential bone regeneration application

Poly(ethylene glycol) hydrogels are currently under investigation as possible scaffold materials for bone regeneration. The main purpose of this research was to analyse the mechanical properties and thermal behaviour of novel photopolymerised poly(ethylene glycol) dimethacrylate (PEGDMA) based hydrogels. The effect of varying macromolecular monomer concentration, molecular weight and water content on the properties of the resultant hydrogel was apparent. For example, rheological findings showed that storage modulus (G′) of the hydrogels could be tailored to a range between approximately 14,000 and 70,000 Pa by manipulating both of the aforementioned criteria. Equally striking variations in mechanical performance were observed using uniaxial tensile testing where reduction in PEGDMA content in the hydrogels resulted in decrease in both tensile strength and Young’s modulus values. Conversely, increases in the elongation at break values were observed as would be expected. Differential scanning calorimetry and dynamic mechanical thermal analysis showed that there was an increase in Tg with an increase in the molecular weight of PEGDMA. The relationship between the initial feed ratio, molecular weight of the macromolecular monomer and the subsequent mechanical properties of the hydrogels are further elucidated throughout this study.     

Preparation of stable insulin-loaded nanospheres of poly(ethylene glycol) macromers and N-isopropyl acrylamide.

A series of nanospheres composed of temperature-sensitive poly(N-isopropylacrylamide), poly(ethylene glycol) 400 dimethacrylate, and poly(ethylene glycol) 1000 methacrylate was prepared by a thermally-initiated free radical dispersion polymerization method. Insulin was loaded into the nanoparticles by equilibrium partitioning. The loading capacity of insulin into the nanoparticles was 2.1% (2.1 mg insulin/100 mg nanoparticles). The stability of the loaded insulin at elevated temperatures was investigated by reverse phase high pressure liquid chromatography. The nanoparticles were able to protect the loaded insulin, as more than 80% of the loaded insulin could still be detected compared to 0% for the control (0.1% insulin solution in PBS) when heated to 80 °C for 5 h. The stability of the loaded insulin at high shear stress (289 1/s) was also investigated. No significant loss of insulin was detected both from nanoparticles loaded with insulin sample and the control (0.1% insulin solution in PBS). The results showed that shear stress alone did not have a major effect on insulin denaturation. The ability of the nanoparticles to protect the insulin from high temperature and high shear stress made the system a good candidate as a carrier for insulin for fluidized bed coating technology.     

Resistance of catheters coated with a modified hydrogel to encrustation during an in vitro test

Summary Mid-shaft specimens were cut from latex catheters coated with a modified hydrogel, latex catheters coated with silicone elastomer, and 100% silicone catheters. These specimens were subjected to controlled in vitro encrustation conditions. During a test period of 11 weeks, there was no significant difference in the quantities of encrusting deposits formed on the three materials.     

载奥沙利铂类弹性蛋白多肽水凝胶的制备及其对小鼠结肠癌CT26细胞的杀伤作用

目的 制备担载奥沙利铂（OXA）的类弹性蛋白多肽（ELPs）水凝胶,研究其体外药物释放情况及对小鼠结肠癌CT26细胞的杀伤作用。 方法 利用大肠杆菌（E.coli）系统表达ELPs原核蛋白,利用可逆相变循环法（ITC）进行蛋白纯化,将ELPs蛋白溶液与交联剂四羟甲基氯化磷（THPC）混匀制备水凝胶,扫描电子显微镜（SEM）观察水凝胶的超微结构,CCK-8法检测不同浓度ELPs水凝胶处理后CT26细胞和小鼠成纤维NIH3T3细胞存活率,活/死细胞染色法观察30和40 g?L^－1 ELPs水凝胶作用48 h后CT26细胞存活情况。制备载OXA的ELPs水凝胶,检测其在不同pH值（6.5和7.4）缓冲液中的药物释放情况,CCK-8法检测加入载不同浓度（0.25、1.00、4.00、16.00和64.00 mg?L^－1）OXA的ELPs水凝胶浸泡液后各组CT26细胞存活率和处理不同时间各组CT26细胞存活率。 结果 凝胶电泳分析,E.coli诱导后在预计相对分子质量38 000附近出现明显加粗的蛋白条带,ITC纯化后泳道中无明显杂蛋白存在。ELPs蛋白溶液中加入THPC后由透明液体状态转变为不透明的白色水凝胶,SEM观察显示出排列整齐的孔隙和三维结构;CCK-8法检测,经不同浓度ELPs蛋白处理后CT26细胞和NIH3T3细胞存活率仍接近100%;活/死细胞染色,ELPs水凝胶处理后的CT26细胞在荧光显微镜下呈现明亮的绿色荧光。载OXA的ELPs水凝胶能在体外持续释放OXA,在pH值6.5条件下OXA的释放速度较pH值7.4条件下稍快;CCK-8法检测,载不同浓度OXA的ELPs水凝胶浸泡液呈剂量依赖性抑制CT26细胞增殖,且随孵育时间的延长CT26细胞存活率逐渐降低。 结论 载OXA的ELPs水凝胶具有持续释放OXA的特性,能够高效且持续地杀伤小鼠结肠癌CT26细胞,可作为一种安全有效的药物递送载体用于抗肿瘤研究。     

Biocompatibility and Recanalization Characteristics of Hydrogel Microspheres with Polyzene-F as Polymer Coating

The objective of this study was to evaluate inflammatory response and recanalization after embolization with a new spherical embolic agent based on a core and shell design with a hydrogel core of polymethylmethacrylate (PMMA) and a Polyzene-F nanoscale coating in a porcine kidney model. Thirty-six minipigs were enrolled for superselective renal embolization. Polyzene-F-coated PMMA particles and uncoated PMMA particles with a diameter of 300-600 mum were used. Either 4 or 12 weeks post-embolization, arteriography of the embolized kidneys was performed and then compared with pre- and immediate post-embolization arteriograms using a specific recanalization score to determine the extent of recanalization. Using a microscopic inflammation score (Banff classification), the embolized organs were examined for local inflammatory effects which occurred in response to the embolic agent. In Polyzene-F-coated particles, the Banff classification showed an average inflammation score of 0.26 +/- 0.58 at 4 weeks and of 0.08 +/- 0.28 at 12 weeks. In uncoated particles, the Banff score measured 0.37 +/- 0.6 at 4 weeks, which was higher, but without a statistically significant difference. According to the recanalization score used in this study, mild angiographic recanalization was evident in all groups, without statistically significant differences (3.0 +/- 0.71 in coated particles, 3.09 +/- 0.81 in uncoated particles; p = 0.74). We conclude that both uncoated hydrogel particles and Polyzene-F-coated embolic agents triggered virtually no inflammatory response and effectively occluded target arteries. This study demonstrates good biocompatibility of the new embolic material. As in other spherical embolic agents, recanalization can occur to some degree.