Ramadon Delly, Permana Andi Dian, Courtenay Aaron J, McCrudden Maelíosa T C, Tekko Ismaiel A, McAlister Emma, Anjani Qonita Kurnia, Utomo Emilia, McCarthy Helen O, Donnelly Ryan F
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia.
Mol Pharm. 2020 Sep 8;17(9):3353-3368. doi: 10.1021/acs.molpharmaceut.0c00431. Epub 2020 Aug 4.
Methicillin-resistant (MRSA) can cause harmful and potentially deadly infections. Vancomycin remains the first-line antibiotic treatment for MRSA-derived infections. Nevertheless, as a peptide drug, it is poorly absorbed when administered orally because of its high molecular weight and low permeability in the gastrointestinal tract and is therefore administered intravenously for the treatment of systemic diseases. In order to circumvent some of the many drawbacks associated with intravenous injection, other routes of drug delivery should be investigated. One of the strategies which has been employed to enhance transdermal drug delivery is based on microarray patches (MAPs). This work, for the first time, describes successful transdermal delivery of vancomycin hydrochloride (VCL) using dissolving MAPs (DMAPs) and hydrogel-forming MAPs (HFMAPs). VCL was formulated into DMAPs and reservoirs [film dosage forms, lyophilized wafers, and compressed tablets (CSTs)] using excipients such as poly(vinyl pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, d-sorbitol, and glycerol. In this study, HFMAPs were manufactured using aqueous blends containing poly(methylvinyl ether--maleic acid) cross-linked by esterification with poly(ethylene glycol). The VCL-loaded CSTs (60% w/w VCL) were the most promising reservoirs to be integrated with HFMAPs based on the physicochemical evaluations performed. Both HFMAPs and DMAPs successfully delivered VCL in studies with the percentage of drug that permeated across the neonatal porcine skin recorded at 46.39 ± 8.04 and 7.99 ± 0.98%, respectively. In studies, the area under the plasma concentration time curve from time zero to infinity (AUC) values of 162.04 ± 61.84 and 61.01 ± 28.50 μg h/mL were achieved following the application of HFMAPs and DMAPs, respectively. In comparison, the AUC of HFMAPs was significantly greater than that of the oral administration control group, which showed an AUC of 30.50 ± 9.18 μg h/mL ( < 0.05). This work demonstrates that transdermal delivery of VCL is feasible using DMAPs and HFMAPs and could prove effective in the treatment of infectious diseases caused by MRSA, such as skin and soft tissue infections, lymphatic-related infections, and neonatal sepsis.
耐甲氧西林金黄色葡萄球菌（MRSA）可引发有害且可能致命的感染。万古霉素仍是治疗MRSA所致感染的一线抗生素。然而，作为一种肽类药物，它口服时因分子量高且在胃肠道中渗透性低而吸收不佳，因此用于治疗全身性疾病时需静脉给药。为了规避静脉注射带来的诸多缺点，应研究其他给药途径。已采用的增强经皮给药的策略之一基于微阵列贴片（MAPs）。这项工作首次描述了使用溶解型微阵列贴片（DMAPs）和水凝胶形成型微阵列贴片（HFMAPs）成功实现盐酸万古霉素（VCL）的经皮给药。VCL使用聚（乙烯基吡咯烷酮）、聚（乙烯醇）、透明质酸钠、d -山梨醇和甘油等辅料被制成DMAPs和储库制剂[薄膜剂型、冻干薄片和压制片（CSTs）]。在本研究中，HFMAPs是使用含有通过与聚（乙二醇）酯化交联的聚（甲基乙烯基醚 - 马来酸）的水性混合物制造的。基于所进行的理化评估，负载VCL的CSTs（60% w/w VCL）是与HFMAPs整合最有前景的储库制剂。在研究中，HFMAPs和DMAPs均成功递送了VCL，经新生猪皮肤渗透的药物百分比分别记录为46.39±8.04%和7.99±0.98%。在研究中，分别应用HFMAPs和DMAPs后，从零到无穷大的血浆浓度 - 时间曲线下面积（AUC）值达到162.04±61.84和61.01±28.50 μg h/mL。相比之下，HFMAPs的AUC显著大于口服给药对照组，口服给药对照组的AUC为30.50±9.18 μg h/mL（P<0.05）。这项工作表明使用DMAPs和HFMAPs经皮递送VCL是可行的，并且可能在治疗由MRSA引起的传染病，如皮肤和软组织感染、淋巴相关感染及新生儿败血症方面有效。
