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

M Wahab Amjad,Mohd Cairul I Mohd Amin,Shalela M Mahali,Ismanizan Ismail,Victor T Giam Chuang,Haliza Katas,M Naeem Ul Hassan

doi:10.1371/journal.pone.0105234

M Wahab Amjad, Mohd Cairul I Mohd Amin + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0105234

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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.

Highlights

Devices and vehicles for drug delivery have made excellent contributions to the improvement of therapeutic outcomes by enhancing the efficacy of established and emerging drugs [1,2,3,4]
We investigated their versatility as carriers of protein and oligonucleotides
We have shown that micelles made from cholic acid-polyethylenimine (CA-PEI) conjugates can be effectively loaded with small interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA)

Summary

Introduction

Devices and vehicles for drug delivery have made excellent contributions to the improvement of therapeutic outcomes by enhancing the efficacy of established and emerging drugs [1,2,3,4]. The hydrophobic core of micelles may be used as a cargo space for the encapsulation of a variety of hydrophobic therapeutic and diagnostic agents Such encapsulation substantially increases their bioavailability and improves their pharmacokinetics and biodistribution. The size of micelles permits their extravasation and accumulation in a variety of pathological sites where the permeability of the vascular endothelium is increased, such as infarct zones and tumors. This fact provides a unique opportunity for physiology-based targeting of drugs and/or drug-loaded pharmaceutical carriers, such as micelles, to these pathological areas via the enhanced permeation and retention (EPR) effect [12,13]. Micelles are easy to prepare on a large scale, providing an additional practical advantage

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