Faculty of Pharmacy and Alternative medicines, the Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan.
Drug Deliv. 2021 Dec;28(1):1569-1584. doi: 10.1080/10717544.2021.1944398.
To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230-550 nm), zeta potential (-15 to -18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12-59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism ( = 0.972-0.976, = 0.326-0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).
为了制备戊二醛交联的中分子量壳聚糖纳米粒包裹 5-氟尿嘧啶（5-FU），克服给药频率，降低药物的急性口服毒性和生物利用度差的问题。采用反胶束法制备中分子量壳聚糖纳米粒（MMWCH-NPs），并用戊二醛（GA）交联进行优化，并通过工艺和配方变量（如不同的药物与聚合物比、交联剂体积、不同的搅拌速度（rpm）、不同的旋转/搅拌时间）进行优化，研究其对平均粒径分布和纳米粒的包封效率%EE和%LC的影响。通过傅里叶变换红外光谱（FTIR）研究、TEM、PXRD、TGA 对制剂进行了表征，通过透析袋技术在 pH（1.2 和 7.4）下进行了稳定性和药物释放研究，在白化兔中进行了急性口服毒性研究。所制备的纳米粒呈光滑形态，粒径分布较小（230-550nm），zeta 电位（-15 至-18mV），这是实现增强渗透和保留效应（EPR）所需的，包封效率（%EE 12-59%）。这些纳米粒显示出一种控制药物释放的特性，在 24 小时内释放了 84.36%的药物。药物释放数据拟合到不同的动力学模型，这些模型主要遵循菲克扩散机制（=0.972-0.976，=0.326-0.256）。在差示扫描量热法/热重分析（DSC/TGA）、TEM、PXRD 曲线、傅里叶变换红外光谱（FTIR）下观察到优化后的制剂（5-FU6），证实了其热稳定性、结构完整性、无定形状态、药物与聚合物的相容性，以及在白化兔中降低了急性口服毒性。交联的中分子量壳聚糖纳米粒是无毒的，耐受性良好，因此可能成为治疗效果的候选物，作为新型药物传递载体用于抗癌药物。
Zotero 插件
