Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution

Autor: Balasrinivasa R. Sajja, Howard E. Gendelman, Dongwei Guo, Xin Ming Liu, Tianyuzi Li, Pavan Puligujja, JoEllyn M McMillan, Michael D. Boska
Rok vydání: 2014
Předmět:
Zdroj: Nanomedicine. 9:1341-1352
ISSN: 1748-6963
1743-5889
Popis: Aim: Drug toxicities, compliance and penetrance into viral reservoirs have diminished the efficacy of long-term antiretroviral therapy (ART) for treatment of HIV infection. Cell-targeted nanoformulated ART was developed to improve disease outcomes. However, rapid noninvasive determination of drug biodistribution is unrealized. To this end, small magnetite ART (SMART) nanoparticles can provide assessments of ART biodistribution by MRI. Materials & methods: Poly(lactic-co-glycolic acid), 1,2-distearoyl-sn-glycero-3-phosphocholine- and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy-PEG 2000)-encased particles were synthesized with atazanavir (ATV) and magnetite. Uptake and retention of ATV and magnetite administered at 3:1 ratios (weight/weight) were determined in human monocyte-derived macrophages and mice. Results: SMART particles were taken up and retained in macrophages. In mice, following parenteral SMART injection, magnetite and drug biodistribution paralleled one another with MRI signal intensity greatest in the liver and spleen at 24 h. Significantly, ATV and magnetite levels correlated. Conclusion: SMART can permit rapid assessment of drug tissue concentrations in viral reservoirs. Original submitted 11 February 2013; Revised submitted 2 April 2013
Databáze: OpenAIRE