Role of pH-sensitive polymer–liposome complex in enhancing cellular uptake of biologically active drugs

In this study, we demonstrate the role of a pH-sensitive polymer–liposome complex in enhancing the delivery and the efficiency of bioactive drugs into cells. For this purpose, we made vesicles composed of poly(methacrylic acid-co-stearyl methacrylate), phosphatidylcholine, and cholesterol. The complex is stable at pH values above 6, but the structure becomes slightly disorganized at pH 5. Below pH 5, the complex readily precipitates. We made drugs-containing (calcein or α-ketoglutaric acid) vesicle dispersions and examined its cellular uptake and biological activity in vitro. Our results indicated that the polymer–liposome complex effectively enhances calcein delivery into human keratinocytes compared to liposome, but both vesicles showed an equal distribution of calcein inside melanocytes. Also, treatment of human dermal fibroblasts by using αKG-containing polymer–liposome complex dispersion significantly enhanced their production of procollagen compared to cells treated with αKG-containing liposome dispersion. The results are discussed by connecting the pH-dependent structural change of this carrier with the acidic environment of endosomes in the cells. Overall, the pH-sensitive polymer–liposome complex prepared in this study appears to be promising for the cytoplasmic delivery of bioactive agents.