Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an effectual groundwork for colorectal cancer.
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.
a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Priyanka
P
Bhatt
a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Nirav
N
Khatri
a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Mukesh
M
Kumar
a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Dipesh
D
Baradia
a Department of Pharmacy, Faculty of Technology & Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
Ambikanandan
A
Misra
D000284:Administration, Oral; D000818:Animals; D002122:Calcium Chloride / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004247:DNA / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D016158:Genes, p53; D015316:Genetic Therapy; D008863:Microspheres; D010368:Pectins / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage* / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000737:chemistry*; D051381:Rats; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical; D014162:Transfection / Q000379:methods
D004337:Drug Carriers; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; C030613:polymethacrylic acid; D010368:Pectins; D004247:DNA; D002122:Calcium Chloride
(wt) p53; Calcium-pectinate; colon targeting; eudragit; non-viral vector