title: Nanoscale Diblock copolymer micelles: characterizations and estimation of the effective diffusion coefficients of biomolecules release through cylindrical diffusion model.
abstract: Biomolecules have been widely investigated as potential therapeutics for various diseases. However their use is limited due to rapid degradation and poor cellular uptake in vitro and in vivo. To address this issue, we synthesized a new nano-carrier system comprising of cholic acid-polyethylenimine (CA-PEI) copolymer micelles, via carbodiimide-mediated coupling for the efficient delivery of small interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA) as model protein. The mean particle size of siRNA- or BSA-loaded CA-PEI micelles ranged from 100-150 nm, with zeta potentials of +3-+11 mV, respectively. Atomic force, transmission electron and field emission scanning electron microscopy demonstrated that the micelles exhibited excellent spherical morphology. No significant morphology or size changes were observed in the CA-PEI micelles after siRNA and BSA loading. CA-PEI micelles exhibited sustained release profile, the effective diffusion coefficients were successfully estimated using a mathematically-derived cylindrical diffusion model and the release data of siRNA and BSA closely fitted into this model. High siRNA and BSA binding and loading efficiencies (95% and 70%, respectively) were observed for CA-PEI micelles. Stability studies demonstrated that siRNA and BSA integrity was maintained after loading and release. The CA-PEI micelles were non cytotoxic to V79 and DLD-1 cells, as shown by alamarBlue and LIVE/DEAD cell viability assays. RT-PCR study revealed that siRNA-loaded CA-PEI micelles suppressed the mRNA for ABCB1 gene. These results revealed the promising potential of CA-PEI micelles as a stable, safe, and versatile nano-carrier for siRNA and the model protein delivery.
authors.affiliation: Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Federal Territory, Malaysia.
authors.forename: M Wahab
authors.initials: MW
authors.lastname: Amjad
authors.affiliation: Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Federal Territory, Malaysia.
authors.forename: Mohd Cairul I
authors.initials: MC
authors.lastname: Mohd Amin
authors.affiliation: School of Informatics & Applied Mathematics, Universiti Malaysia Terengganu, Kuala Terengganu, Terengganu, Malaysia.
authors.forename: Shalela M
authors.initials: SM
authors.lastname: Mahali
authors.affiliation: Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Federal Territory, Malaysia.
authors.forename: Haliza
authors.initials: H
authors.lastname: Katas
authors.affiliation: Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
authors.forename: Ismanizan
authors.initials: I
authors.lastname: Ismail
authors.affiliation: Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
authors.forename: M Naeem Ul
authors.initials: MN
authors.lastname: Hassan
authors.affiliation: School of Pharmacy, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia.
authors.forename: Victor T Giam
authors.initials: VT
authors.lastname: Chuang
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D006224:Cricetinae; D006801:Humans; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D008823:Micelles; D011108:Polymers; D034741:RNA, Small Interfering; D012710:Serum Albumin, Bovine