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Cholesterol-grafted chitosan micelles as a nanocarrier system for drug-siRNA co-delivery to the lung cancer cells

Author:
Muddineti, Omkara Swami, Shah, Aashma, Rompicharla, Sri Vishnu Kiran, Ghosh, Balaram, Biswas, Swati
Source:
International journal of biological macromolecules 2018 v.118 pp. 857-863
ISSN:
0141-8130
Subject:
adverse effects, chitosan, cholesterol, curcumin, drug therapy, drugs, endocytosis, ethidium, gel electrophoresis, human cell lines, hydrophobicity, lung neoplasms, micelles, molecular weight, nanocarriers, nanoparticles, neoplasm cells, particle size, small interfering RNA, zeta potential
Abstract:
Combined delivery of a therapeutic small interfering RNA (siRNA) and a chemotherapeutic agent to cancer cells is promising as anticancer therapy, which could offer enhanced cell killing potential and low side effect. However, simultaneous delivery to tumor is challenging. In our study, cholesterol-modified low molecular weight chitosan (MW ~ 15 kDa) was employed as a self-assembled delivery system for both siRNA and a hydrophobic chemotherapeutic agent, curcumin to cancer cells. The siRNA/curcumin loaded nanoparticles (C-CCM/siRNA) were physico-chemically characterized for particle size (165 ± 2.6 nm) and zeta potential (+24.8 ± 2.2 mV). The ability of CCM to condense siRNA was determined by ethidium bromide exclusion and gel retardation assay using electrophoresis. The result demonstrated that the condensation of C-CCM with siRNA was optimum at minimum N/P ratio of 40. C-CCM/siRNA was stable at 4 °C for a period of >1 month. C-CCM/siRNA was taken up efficiently by human lung carcinoma cells, A549 in a time-dependent manner. The cellular internalization of C-CCM/siRNA was observed via clathrin-mediated endocytosis as determined by using specific endocytosis inhibitors. The study demonstrated the feasibility of the use of cholesterol conjugated chitosan as a co-delivery system for both siRNA and a hydrophobic drug for combination cancer therapy.
Agid:
6052921