K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose.

Andre-I Sarabia-Sainz,Ana Guzman-Partida,Veronica Mata-Haro,Luz Vazquez-Moreno,Gabriela Montfort,Roberto Guzman,Hector Sarabia-Sainz,Mariano Garcia-Soto

doi:10.3390/ijms160922425

Abstract

The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.

Highlights

In the last few decades, drug delivery technology has gained great interest in the pharmaceutical industry
Albumin modified with lactose (BSA-Lac) was used as the polymer for the synthesis of lactosylated albumin microspheres [14,15]
Three formulations labeled as MS-Lac1, MS-Lac2 and MS-Lac3, obtained by water-in-oil emulsion at three concentrations of crosslinker were imaged by scanning electron microscopy

Summary

Introduction

In the last few decades, drug delivery technology has gained great interest in the pharmaceutical industry. Drug carriers, such as liposomes, nanoparticles and microspheres, are systems based in biodegradable and biocompatible polymers [1]. These systems of controlled drug delivery offer advantages over conventional methods of drug administration, namely drug protection, control delivery and patient compliance [2]. Langer and Farokhzad Laboratories working with drug-loaded polymeric nanoparticles coated with aptamers targeting tumor-specific cells have shown that such constructs can enhance selective killing of tumor cells [6,7]

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