Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an effectual groundwork for colorectal cancer

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 Õ 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.

Coadministration of Polypeptide-k and Curcumin Through Solid Self-Nanoemulsifying Drug Delivery System for Better Therapeutic Effect Against Diabetes Mellitus: Formulation, Optimization, Biopharmaceutical Characterization, and Pharmacodynamic Assessment

“…In addition to that, formation of complex film of surfactant and cosurfactants around the droplets contributes to stability of droplets by strengthening their interfacial film. 5,25 It could also be attributed to the better solubility of both the poorly soluble drugs in oil; the surfactant and cosurfactants reduce the interfacial tension upon dispersion of drugs in aqueous medium. In case of PPK-CRM SNEDDS, an increase in zeta potential was observed toward negative side at higher level of oil, surfactant, and cosurfactant whereas, in case of only PPK-SNEDDS, the zeta potential was decreased at higher levels of oil and cosurfactant.…”

“…The study was carried out in hexaplicate and mean data -SD (standard deviation) was recorded. 5,21,24,25 Ex vivo diffusion studies. Intestine of 24-h fasting goat was collected from a local slaughterhouse and used for permeation study.…”

Applications liposome in cancer drug delivery and treatment: A review

“…Also, liposome can be combination of ligands and opsonin to activate endocytosis. Designed liposomes can be used for transformation of DNA 16 which is known as lipofection. Liposomes can be used in many other delivery systems such as Pesticides to plants, Cosmetics to the skin, Dyes to textiles etc.…”

Liposomal Formulations In Cancer Therapy: Passive Versus Active Targeting

“…Therefore, numerous research and studies have been carried out for immunoliposomes for the cancer treatment by targeted drug delivery for various types of cancer disease such as breast cancer, colorectal cancer, lung cancer, etc. 11,12 . The function of immunoliposomes in cancer treatment is to reduce the accumulation of drug in healthy tissues and increase the drug delivery to tumour by antibodymediated guiding of the liposomes 13,14 .…”