Wang Shiqi, Attah Reva, Li Jiali, Chen Yitong, Chen Rongjun
Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
ACS Biomater Sci Eng. 2018 Dec 10;4(12):4236-4243. doi: 10.1021/acsbiomaterials.8b01040. Epub 2018 Oct 10.
Oral administration is a noninvasive and convenient drug delivery route most preferred by patients. However, poor stability in the gastrointestinal tract and low bioavailability of hydrophobic drugs has greatly limited their oral administration. To address this problem, we report a pH-responsive, amphiphilic hydrogel drug carrier based on a pseudopeptide poly(l-lysine isophthalamide) (PLP) and poly(ethylene glycol) (PEG). The hydrogels were prepared by a simple -(3-(dimethylamino)propyl)-'-ethyl carbodiimide hydrochloride (EDC)/-hydroxysuccinimide (NHS) coupling reaction, and the cross-linking was confirmed by infrared spectroscopy and differential scanning calorimetry analyses. Because of the pH-responsive conformational alteration of PLP, the hydrogels were relatively hydrophobic and collapsed at acidic pH, but became hydrophilic and swollen at neutral pH. The amphiphilicity enabled the hydrogels to well retain and protect hydrophobic model drugs in the simulated gastric fluid, but efficiently release them in the simulated intestinal fluid. These results suggested that the pH-responsive amphiphilic hydrogels are promising candidates for oral delivery of hydrophobic drugs.
口服给药是一种无创且方便的给药途径，是患者最为青睐的方式。然而，胃肠道中稳定性差以及疏水性药物生物利用度低极大地限制了它们的口服给药。为了解决这一问题，我们报道了一种基于假肽聚（间苯二甲酰-L-赖氨酸）（PLP）和聚乙二醇（PEG）的pH响应型两亲性水凝胶药物载体。通过简单的盐酸-(3-(二甲氨基)丙基)-'-乙基碳二亚胺（EDC）/N-羟基琥珀酰亚胺（NHS）偶联反应制备水凝胶，并通过红外光谱和差示扫描量热法分析确认交联情况。由于PLP的pH响应构象改变，水凝胶相对疏水，在酸性pH下会塌陷，但在中性pH下会变得亲水并溶胀。两亲性使水凝胶能够在模拟胃液中很好地保留和保护疏水性模型药物，但在模拟肠液中能有效释放它们。这些结果表明，pH响应型两亲性水凝胶有望成为口服递送疏水性药物的候选材料。
