Abstract
Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.
Highlights
Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery.[1]
We aimed at synthesizing long-circulating PEGylated poly(lactic-co-glycolic acid) (PLGA) conjugates which are capable of encapsulating curcumin for subsequent cancer therapy in vivo
It was hypothesised that the inclusion of an oil core into the polymeric NC will offer superior drug loading compared to other nanoformulations, while polymer PEGylation can prolong the blood circulation profile, maximizing the enhanced permeation and retention in solid tumors so that the drug can reach the tumor at high concentrations
Summary
Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery.[1] These features have made biodegradable polymeric nanocpasules (NCs) one of the most widely used. They can achieve high water insoluble drug loading, facilitate. I. El-Gogary Department of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Ain Shams University Khalifa El-Maamon Street, Abbasiya Square, Cairo 11566, Egypt. T. Al-Jamal School of Pharmacy University of East Anglia Norwich Research Park, Norwich NR4 7TJ, UK
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