Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, United Kingdom.
Biomater Adv. 2024 Nov;164:213995. doi: 10.1016/j.bioadv.2024.213995. Epub 2024 Aug 12.
This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A ∼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a ∼ 1.78 and ∼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.
本研究旨在制备基于新型生物材料的活性微针（MN）贴片，并评估其对模型药物（Linezoid）的有效耦合（物理和电）透皮递送。采用真空微成型法制备改良 MN 贴片（例如由 Linezoid、硼化壳聚糖、聚乙烯醇和 D-山梨糖醇制成）。对制备的配方进行物理化学、傅里叶变换红外（FTIR）、计算机模拟、结构和热分析，以确定 MN 的质量、组成和完整性。进行体外机械试验、膜毒性、药物释放、抗生物膜、离体黏膜黏附、插入和体内抗生物膜研究，以进一步验证耦合系统的可行性。优化的 MN 贴片配方（CSHP3-包含 3%w/v 硼化壳聚糖、3.5%w/v PVA 和 10%w/w D-山梨糖醇）具有锋利的尖端、等距和均匀表面的微米级突起，具有一致的物理化学特征。FTIR 分析证实了壳聚糖的修饰（即硼化）以及 CSHP3 成分的相容性和相互作用。计算机模拟分析表明所有配方成分之间存在非共价相互作用。此外，硼化壳聚糖-粘蛋白糖蛋白复合物的结合强度（CScore 高约 1.86 倍）强于利奈唑胺-粘蛋白对应物。热分析表明 CSHP3 具有无定形性质。CSHP3 的拉伸强度比对照（即纯壳聚糖、聚乙烯醇和基于 D-山梨糖醇的 MN 贴片）高约 1.42 倍。膜毒性研究表明 CSHP3 具有非毒性和生理相容性。在 90 分钟内，91.99±2.3%的利奈唑胺从 CSHP3 中释放出来。在琼脂糖凝胶上的释放研究中，与 CSHP3 单独处理相比，CSHP3-离子电渗处理在 60 分钟内分别导致甲基蓝覆盖面积和光密度增加约 1.78 倍和 1.20 倍。用 CSHP3 处理的金黄色葡萄球菌生物膜的质量减少了 65±4.2%。CSHP3 MN 贴片在兔子口腔黏膜上的黏附时间为 6±0.15 h。用 CSHP3 和 CSHP3-离子电渗联合处理的黏膜显示出在上皮层中产生了通路，而对下面的固有层没有任何损伤。用 CSHP3-离子电渗联合方法治疗 7 天后，记录到从口腔黏膜伤口中消除金黄色葡萄球菌和完全组织再生。
