Targeted Drug Delivery Using Silica Xerogel Systems To Treat Diseases Due To Intracellular Pathogens

Intracellular bacterial pathogens like Salmonella, Brucella, Mycobacterium and Listeria have developed various mechanisms to invade host cells, and they can establish persistent infections. Treatment and eradication are difficult in vivo due to its localization at the cellular level and many of the available antimicrobials cannot efficiently penetrate cell membrane. Development of a method to effectively deliver the drug in to phagocytic cells is the use of carrier system that will encapsulate the drug, transport them to the target cell and release the drugs within the cells where they can reach the intracellular bacteria. The recently developed sol-gel technique offers new possibilities for embedding organic compounds within a porous silica matrix and for controlling their release from the host matrix into a surrounding medium. We investigated a sol-gel derived silica xerogel as a delivery system for the prolonged release of gentamicin for treatment of Salmonella infection in a mouse model. The particle sizes of our porous silica are in a broad range from 1.7 to 3.3 mu m. The release of gentamicin from the inside hollow part of the porous carrier can last a comparatively long time, leading to a delayed release of the drug (90% of gentamicin released in 5 days). Administration of three doses of porous silica loaded with gentamicin reduced the CFU of S. thyphimurium in livers of infected mice by 0.48 log compared to 0.13 log with free drug. This new approach, utilizing sol-gel carrier systems for drug delivery, should improve our capability for targeting intracellular pathogens. (C) 2009 Elsevier B.V. All rights reserved.