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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
Published on: August 6, 2019
Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an effectual groundwork for colorectal
Priyanka Bhatt1, Nirav Khatri1, Mukesh Kumar1
1a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Abstract:
This study was aimed to develop and evaluate p53 polyplex-loaded enteric-coated calcium pectinate microbeads for oral gene delivery as an effective novel alternative for colorectal cancer therapy. Mutation in p53 is the key event in colorectal cancer (CRC) and an important target for the treatment of CRC through gene therapy. Polymethacrylates-based non-viral vectors were evaluated for their ability to complex, protect and transfect p53 (wt) into colon cancer cell line. Polyplexes were formulated by complexation of cationic polymer with anionic pDNA at different N/P ratios. p53 polyplex-loaded calcium pectinate (CP) microbeads were prepared by ionotropic gelation of pectin with calcium chloride and coated with Eudragit® S100. In vitro release studies showed that enteric-coated CP microbeads protected the release of p53 polyplex in upper GIT with less than 10% release. In-vitro cell line studies and in vivo studies in rat showed that polymethacrylate carrier could transfect the pDNA effectively. Results of in vivo gene expression study further confirmed the ability of enteric-coated calcium pectinate microbeads to deliver pDNA specifically to rat colon. Conclusively, enteric-coated calcium pectinate microbeads released p53 polyplex specifically in colon and could serve as an effective alternative for CRC therapy.
Insights
New enteric-coated microbeads deliver p53 gene therapy directly to the colon for colorectal cancer treatment. This oral delivery system shows promise for effective cancer therapy.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Cancer Research
Background:
- Colorectal cancer (CRC) is often linked to p53 gene mutations, making it a key target for gene therapy.
- Developing effective oral gene delivery systems for CRC treatment remains a significant challenge.
Purpose of the Study:
- To create and assess p53 polyplex-loaded enteric-coated calcium pectinate microbeads for oral gene delivery.
- To establish a novel therapeutic alternative for colorectal cancer.
Main Methods:
- Formulation of p53 polyplexes using polymethacrylates and pDNA at varying N/P ratios.
- Preparation of enteric-coated calcium pectinate (CP) microbeads via ionotropic gelation and Eudragit® S100 coating.
- In vitro and in vivo evaluation of pDNA transfection efficiency and colon-specific delivery.
Main Results:
- Enteric-coated CP microbeads demonstrated minimal (<10%) p53 polyplex release in the upper gastrointestinal tract.
- In vitro and in vivo studies confirmed effective pDNA transfection by the polymethacrylate carrier.
- In vivo gene expression studies validated specific pDNA delivery to the rat colon.
Conclusions:
- Enteric-coated calcium pectinate microbeads facilitate targeted p53 polyplex release within the colon.
- This novel oral delivery system presents a viable and effective strategy for colorectal cancer gene therapy.
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