Abstract:
:We have shown that nanoparticles (NPs) conjugated to trans-activating transcriptor (TAT) peptide bypass the efflux action of P-glycoprotein and increase the transport of the encapsulated ritonavir, a protease inhibitor (PI), across the blood-brain-barrier (BBB) to the central nervous system (CNS). A steady increase in the drug parenchyma/capillary ratio over time without disrupting the BBB integrity suggests that TAT-conjugated NPs are first immobilized in the brain vasculature prior to their transport into parenchyma. Localization of NPs in the brain parenchyma was further confirmed with histological analysis of the brain sections. The brain drug level with conjugated NPs was 800-fold higher than that with drug in solution at two weeks. Drug clearance was seen within four weeks. In conclusion, TAT-conjugated NPs enhanced the CNS bioavailability of the encapsulated PI and maintained therapeutic drug levels in the brain for a sustained period that could be effective in reducing the viral load in the CNS, which acts as a reservoir for the replicating HIV-1 virus.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Rao KS,Reddy MK,Horning JL,Labhasetwar Vdoi
10.1016/j.biomaterials.2008.08.004subject
Has Abstractpub_date
2008-11-01 00:00:00pages
4429-38issue
33eissn
0142-9612issn
1878-5905pii
S0142-9612(08)00567-Xjournal_volume
29pub_type
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