Synthesis and Properties of New Multilayer Chitosan@layered Double Hydroxide/Drug Loaded Phospholipid Bilayer Nanocomposite Bio-Hybrids.

Dan A Lerner,Didier Tichit,Jean-Marie Devoisselle,Thierry Azaïs,Ramona Polexe,Anne Aubert-Pouëssel,Sylvie Bégu

doi:10.3390/ma13163565

Abstract

A novel bio-hybrid drug delivery system was obtained involving a Mg/Al-NO3 layered double hydroxide (LDH) intercalated either with ibuprofenate anions (IBU) or a phospholipid bilayer (BL) containing a neutral drug, i.e., 17β-estradiol, and then embedded in chitosan beads. The combination of these components in a hierarchical structure led to synergistic effects investigated through characterization of the intermediates and the final bio-composites by XRD, TG, SEM, and TEM. That allowed determining the presence and yield of IBU and of BL in the interlayer space of LDH, and of the encapsulated LDH in the beads, as well as the morphology of the latter. Peculiar attention has been paid to the intercalation process of the BL for which all available data substantiate the hypothesis of a first interaction at the defect of the LDH, as well as on the interaction mode of these components. 1H, 31P and 27Al MAS-NMR studies allowed establishing that the intercalated BL is not homogeneous and likely formed patches. Release kinetics were performed for sodium ibuprofenate as well as for the association of 17β-estradiol within the negatively charged BL, each encapsulated in the LDH/chitosan hybrid materials. Such new bio-hybrids offer an interesting outlook into the pharmaceutical domain with the ability to be used as sustained release systems for a wide variety of anionic and, importantly, neutral drugs.

Highlights

Organic-inorganic hybrid materials formed by intercalation of anionic drugs into the interlayer spaces of layered double hydroxides (LDH) have recently gained much attention in the pharmaceutical domain due to several useful properties such as high drug loading, biocompatibility, enhanced cellular uptake, and delivery efficiency by anionic exchange or dissolution of the LDH matrix
We first report on the preparation and characterization of beads of chitosan loaded with bio-hybrids formed by LDH exchanged with ibuprofen (IBU) in its anionic form. We extended this approach to new drug-carrying nanocomposites made from beads of chitosan containing LDH
The present work describes a novel drug delivery system based on LDH loaded with the drug and trapped into chitosan beads

Summary

Introduction

Organic-inorganic hybrid materials formed by intercalation of anionic drugs into the interlayer spaces of layered double hydroxides (LDH) have recently gained much attention in the pharmaceutical domain due to several useful properties such as high drug loading, biocompatibility, enhanced cellular uptake, and delivery efficiency by anionic exchange or dissolution of the LDH matrix. LDH, named anionic clays or hydrotalcite-like materials, existing as natural minerals, are more commonly synthesized in the laboratory. They consist of brucite-like sheets based on octadedrally coordinated metallic cations (M2+ and M3+ ) surrounded by hydroxyl groups, held together by the presence of exchangeable anions (An- ) and a variable number of water molecules in the interlayer space. Many pharmaceutically active compounds negatively charged at the physiological pH have been intercalated in LDH, forming two-component nanoparticles.

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