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J Control Release. 2008 May 22;128(1):60-70. doi: 10.1016/j.jconrel.2008.02.014. Epub 2008 Mar 5.

Molecular interactions, internal structure and drug release kinetics of rationally developed polymer-lipid hybrid nanoparticles.

Author information

1
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.

Abstract

This paper presents the first study of molecular interactions of ingredients and internal nanostructure in relation to drug loading and release mechanisms/kinetics of rationally designed solid polymer-lipid hybrid nanoparticles (PLN). The PLN were prepared by using a rationally selected composition that was found in our previous work to provide optimized interactions of verapamil hydrochloride (VRP) with dextran sulfate sodium (DS) and then the VRP-DS complex with dodecanoic acid (DA). The solid-state properties of the components, their molecular interactions and the morphology, particle size and internal structure of PLN were determined by use of differential scanning calorimetry, powder X-ray diffraction, (13)C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The distribution of VRP in PLN was examined by TEM imaging using a cationic gold tracer. Drug release studies were conducted in various media. Drug loading as high as 36% and loading efficiencies up to 99% were achieved in the rationally formulated PLN. Hydrogen bonding between drug, polymer and lipid and a uniform distribution of amorphous VRP within the solid lipid matrix were evident. Sustained drug release from the PLN was mainly controlled by ion exchange and diffusion processes. The results demonstrated that strong molecular interactions among the drug, the polymer and the lipid in the optimized formulation were responsible for the improved drug loading and release performance of the PLN.

PMID:
18406489
DOI:
10.1016/j.jconrel.2008.02.014
[Indexed for MEDLINE]

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