Leishmaniasis is still a serious public health problem worldwide, especially in tropical areas where this infectious disease is endemic. The most severe form of the disease (i.e. visceral) can claim victims if left untreated and the few accessible drugs have several drawbacks including major side effects and parenteral administration. In this context, the investigation of new delivery modalities which might reduce the toxicity and increase the bioavailability of the drugs currently on the market represents a valid strategy to counter these problems. Herein we present the development of a macrophage mediated drug targeting delivery system by conjugating the anti-leishmanial drug pentamidine (Pent) with the biocompatible polymer hyaluronic acid (HA), the latter employed at the same time as a delivery platform and targeting scaffold. Biological assays against Leishmania major amastigote-infected macrophages and primary bone marrow derived macrophages (BMDM) confirmed the validity of our strategy as the resulting bioconjugate HA-Pent increased both the potency and the selectivity index of the drug

A hyaluronic acid–pentamidine bioconjugate as a macrophage mediated drug targeting delivery system for the treatment of leishmaniasis

MICALE, Nicola
Primo
;
PIPERNO, Anna
Secondo
;
SCALA, ANGELA
Penultimo
;
GRASSI, Giovanni
Ultimo
2015-01-01

Abstract

Leishmaniasis is still a serious public health problem worldwide, especially in tropical areas where this infectious disease is endemic. The most severe form of the disease (i.e. visceral) can claim victims if left untreated and the few accessible drugs have several drawbacks including major side effects and parenteral administration. In this context, the investigation of new delivery modalities which might reduce the toxicity and increase the bioavailability of the drugs currently on the market represents a valid strategy to counter these problems. Herein we present the development of a macrophage mediated drug targeting delivery system by conjugating the anti-leishmanial drug pentamidine (Pent) with the biocompatible polymer hyaluronic acid (HA), the latter employed at the same time as a delivery platform and targeting scaffold. Biological assays against Leishmania major amastigote-infected macrophages and primary bone marrow derived macrophages (BMDM) confirmed the validity of our strategy as the resulting bioconjugate HA-Pent increased both the potency and the selectivity index of the drug
2015
File in questo prodotto:
File Dimensione Formato  
RSC-2015.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 499.33 kB
Formato Adobe PDF
499.33 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3065338
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 19
social impact