Umamaheshwari R B, Jain N K
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar (M.P.) 470 003, India.
J Control Release. 2004 Sep 14;99(1):27-40. doi: 10.1016/j.jconrel.2004.06.006.
In the present context, phosphatidyl ethanolamine (PE) liposomes anchored polyvinyl alcohol (PVA) xerogel beads (lipobeads) bearing acetohydroxamic acid (AHA) was developed as a receptor-mediated drug delivery system for use in blocking adhesion of Helicobacter pylori and thereby preventing the sequelae of chronic gastric infections. PVA beads containing AHA were prepared by emulsification followed by low temperature crystallization method. Surface acylation with fatty acid chain was accomplished by treating PVA bare beads with palmitoyl chloride. The completion of this reaction was characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) which confirmed the formation of an ester bond. Final formation of lipobeads was accomplished by combining acylated PVA beads with a PE liposome suspension. To confirm the specific binding propensity of lipobeads towards the PE specific surface receptors of H. pylori, we have performed in situ adherence assay and radiolabelling assay with human stomach cells and KATO-III cells, respectively. In both of these studies, pretreatment of H. pylori with lipobeads completely inhibited the adhesion of H. pylori to human stomach cells and KATO-III cells. These assays could serve as suitable in-vitro models for the study of binding efficacy of lipobeads with H. pylori surface receptors. In addition, the antimicrobial activity of the formulations was evaluated by growth inhibition (GI) studies with isolated H. pylori strain. The inhibitory efficacy of lipobeads was significantly higher compared to that of PVA bare beads. These results suggest that lipobeads could be a potential targeted drug delivery system in the treatment of H. pylori.
在当前背景下，开发了一种以磷脂酰乙醇胺（PE）脂质体锚定的负载乙酰氧肟酸（AHA）的聚乙烯醇（PVA）干凝胶珠（脂质珠）作为受体介导的药物递送系统，用于阻断幽门螺杆菌的黏附，从而预防慢性胃部感染的后遗症。含AHA的PVA珠通过乳化后低温结晶法制备。用棕榈酰氯处理PVA裸珠完成脂肪酸链的表面酰化。该反应的完成通过衰减全反射傅里叶变换红外光谱（ATR-FTIR）表征，其证实了酯键的形成。脂质珠的最终形成通过将酰化的PVA珠与PE脂质体悬浮液混合来完成。为了确认脂质珠对幽门螺杆菌PE特异性表面受体的特异性结合倾向，我们分别用人胃细胞和KATO-III细胞进行了原位黏附试验和放射性标记试验。在这两项研究中，用脂质珠对幽门螺杆菌进行预处理完全抑制了幽门螺杆菌对人胃细胞和KATO-III细胞的黏附。这些试验可作为研究脂质珠与幽门螺杆菌表面受体结合效果的合适体外模型。此外，通过对分离的幽门螺杆菌菌株进行生长抑制（GI）研究来评估制剂的抗菌活性。脂质珠的抑制效果明显高于PVA裸珠。这些结果表明脂质珠可能是治疗幽门螺杆菌的一种潜在靶向药物递送系统。
