Abstract
Objective: Chitosan nanoparticles (ChNP’s) have been widely studied for drug and gene delivery. In this study, we prepared ChNP’s for co-delivery of doxorubicin (DOX) and siRNA for cancer treatment.
 Methods: The ionic gelation method was used to develop ChNP’s. The positively charged DOX and negatively charged siRNA encapsulated into ChNP’s. The particle size and zeta potential of the developed ChNP’s were studied by particle size analyzer and morphology was examined by TEM. Encapsulation of DOX in ChNP’s was confirmed by FTIR spectroscopy. The encapsulation efficiency and in vitro release of DOX were studied by UV-Vis spectrophotometry. The siRNA loading into ChNP’s was confirmed by gel retardation assay.
 Results: The developed ChNP’s showed particle size ranged from 127±6.5 to 215±8.5 nm with zeta potential ranged from 16.5±0.3 to 25.8±0.3. Transmission Electron Micrograph showed DOX and siRNA encapsulated ChNP’s are polydisperse and spherical in nature. FTIR study confirmed the binding of DOX with ChNP’s with absorption peaks at 1016 cm-1,1316 cm-1, 1412 cm-1, 1645 cm-1 and 3370 cm-1. The TPP:Ch ratio 0.1:0.5 showed the highest encapsulation efficiency 69±3.24%, with initial burst release and then sustained or slow release of DOX. Agarose gel retardation study confirmed the encapsulation of siRNA in ChNP’s by retarded migration of siRNA-ChNP’s in comparison with naked siRNA.
 Conclusion: The developed ChNP’s successfully encapsulated the DOX and siRNA and showed the sustain release of DOX. In conclusion, our study shown that ChNP’s is having a potential of co-loading of DOX-siRNA as an efficient drug delivery system for the treatment of various cancers such as colorectal cancer, breast cancer etc.
Highlights
A days, cancer is one of the main causes of death worldwide
RNA interference (RNAi) is a cellular mechanism for gene suppression induced by siRNA in which 21-23 base pairs sequence of siRNA complementary to its target mRNA, which acts as a post-transcriptional regulator [10]
The results revealed that Ch:TPP ratio 0.1:0.5 was found optimum on the basis of maximum percentage DOX encapsulation efficiency (69±3.24 %) with optimum size and distribution (192±8.1 and 0.62±0.05)
Summary
Cancer is one of the main causes of death worldwide. Conventional therapies such as radiotherapy, surgery, chemotherapy and a combination of them are used to treat cancer [1]. Problems related to acquired resistance and their acute cardiotoxicity, low penetration and limited distribution in solid tumor [4, 5]. Due to this side effects use of free DOX in the biomedical field is still limited. Nanocarrier based drug delivery systems offer several advantages, including the greater surface area of nanoparticles, due to reduced size, sustained drug release rate, improvement in biodistribution, and reduction in side effects [6, 7]. Polymeric nanoparticles are most studied carriers in drug delivery, which exhibits pH-responsive, drug retaining ability during circulation and releasing it at the tumor site. Even the use of siRNAs that target particular genes has been shown to reduce resistance problems. Most practical applications need a carrier to transport the siRNA via systemic application to the target site [11,12,13]
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