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New nanoparticles for the delivery of antibiotics to fight antimicrobial-resistance

AlbuminAntibioticscolistindrug-resistanceNanoparticles

Introduction

The antimicrobial resistance phenomenon has long been an important sanitary emergency, making it necessary to resort to “last choice” antibiotics such as colistin, little used due to toxicity and poor penetrability at sites of infection. To counteract this we developed a new drug delivery system able to reduce toxicity, increase efficacy and overcome antimicrobial resistance.

Technical features

The nanoparticles we have developed consist of a lipophilic multireservoir containing the molecularly dispersed colistin. The formulation consists of albumin, a biocompatible substance, with reduced costs compared to other formulations containing phospholipids, coated with chitosan, which increases its mucoadhesive properties. The formulation is neither toxic nor haemolytic, it is highly stable and allows a prolonged release of the drug over time. The manufacturing process is short, not complex and easily scalable, reducing the production costs. Respect to other albumin nanoparticles currently in use, as antitumoral drug, this formulation is innovative as the colistin is not chemically bound to the albumin. The results obtained in in vitro experiments with this new delivery system show an increased antimicrobial and antibiofilm activity (a significant reduction of the MIC value from 4 to 10 times compared to free colistin, and a 60-fold MBIC50 lower than MBIC50 of free colistin), towards colistin resistant and sensible bacteria.

Possible Applications

  • Topical treatment of skin infections in burn patients;
  • Topical treatment of chronic wounds and ulcers;
  • Inhalation/nebulization treatment  of chronic respiratory infections in cystic fibrosis patients.

Advantages

  • Low costs of production;
  • Short production times;
  • Possible use of the two forms of colistin: colistin sulphate and methanesulfonate;
  • Prolonged release of the drug over time.