Nanoscale Diblock copolymer micelles: characterizations and estimation of the effective diffusion coefficients of biomolecules release through cylindrical diffusion model

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 (...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one Vol. 9; no. 8; p. e105234
Main Authors:	Amjad, M Wahab, Mohd Amin, Mohd Cairul I, Mahali, Shalela M, Katas, Haliza, Ismail, Ismanizan, Hassan, M Naeem Ul, Chuang, Victor T Giam
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 18-08-2014 Public Library of Science (PLoS)
Subjects:	Acids Analysis Animals Atomic force microscopy Biochemistry Biology and life sciences Biomolecules Bovine serum albumin Carbodiimide Cattle Cell Line, Tumor Chemical synthesis Cholic acid Controlled release Copolymers Cricetinae Cytotoxicity Diffusion Diffusion coefficient Drug delivery systems Electron microscopy Engineering and Technology Field emission microscopy Humans Macular degeneration Mathematical models Mathematical morphology Medicine and Health Sciences Micelles Microscopy, Electron, Transmission Morphology mRNA Pharmaceuticals Polyethyleneimine Polymerase chain reaction Polymers - chemistry Respiratory syncytial virus RNA RNA, Small Interfering - chemistry Scanning electron microscopy Serum albumin Serum Albumin, Bovine - chemistry siRNA Sustained release Kuala Lumpur Malaysia Malaysia Terengganu Malaysia Selangor Malaysia United States > US
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: MWA MCIMA. Performed the experiments: MWA MNUH SMM. Analyzed the data: MWA SMM MCIMA. Contributed reagents/materials/analysis tools: MCIMA HK SMM II VTGC. Contributed to the writing of the manuscript: MWA SMM MCIMA. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0105234