Development and evaluation of amphiphilic heterolipid based pH-sensitive nanomicelles of doxorubicin

Abstract

Although with limited success, drug delivery approaches particularly lipid-based nano-drug delivery systems (LBNDDS) is frequently considered to address drug toxicity problem in cancer chemotherapy. Design, synthesis and evaluation of nitrogen containing heterolipids is present area of our research. In the present paper investigations to evaluate the potential of few such synthesized heterolipids in nano-drug delivery systems are recorded. The heterolipids were studied for their self-assembling properties, pH dependent characteristics and potential as intracellular drug delivery nanocarriers using doxorubicin as a model drug. Among tested heterolipids, HLysA-3 with critical micellar concentration (CMC) of 40 μM and pKa of 7.74 was found to have maximum drug loading of 24.85% w/w with an excellent quantitative encapsulation efficiency. The nanomiceller formulation, doxorubicin-HLysA-3 (DOX-HLysA-3) developed using HLysA-3 was found to be pH dependent. At physiological pH 7.4, the nanomicelles were more stable with incomplete drug release than at acidic pH 5.0, where instability of the nanomicelles resulted in complete drug release. HLysA3 was found to be nontoxic with equipotent anti-tumor activity as arbitrated by growth inhibition of 50% (GI₅₀) value of <10 μg/mL to marketed DOX formulation Adriamycin® against HeLa, MCF-7, and PC-3 cell lines. To summarize, our designed and synthesized heterolipid HLysA-3 can form self-assemblies of nanomicelles with doxorubicin and have pH-sensitive drug release, indicating that it could be a promising cancer therapy candidate.