Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries

In vitro dissolution/release methods for mucosal delivery systems

“…This setup is widely employed for in vitro drug release testing from ocular inserts [50] and contact lenses [51]. Sometimes is also used in case of semisolid dosage forms [6], microparticles for nasal application [52] and thermosensitive gels for buccal application [53]. This apparatus allows the drug release testing under physiological flow rate of the dissolution medium and offers ability to maintain the sink conditions while operating in an open system setup.…”

Intranasal chitosan-g-HPβCD nanoparticles of efavirenz for the CNS targeting

“…According to Hanson and Frey, IN delivery of ARV could be used in prevention and treatment of neuro-AIDS [5]. Literature indicates successful delivery ARV by IN routes, Abeer M. Al-Ghananeem and coworkers [6] have formulated didanosine-chitosan nanoparticles with increased drug delivery in the CNS, Barbi et al [7] prepared zidovudinchitosan nanoparticles for IN delivery, Dalpiaz A. and coworkers has conjugated zidovudine to ursodeoxycholic acid to produce prodrug which remained in murine macrophages 20 times higher than zidovudine and designed chitosan chloride microparticles had more CSF uptake in rat [8], Mahajan et al [9] developed saquinavir mesylate nanoemulsion and Chiappetta et al [10] developed efavirenz poly(ethylene oxide)-poly(propylene oxide) polymeric micelles with fivefold increase in bioavailability of drug compared to intravenous (i.v.) administration.…”

Advancements in nano-enabled therapeutics for neuroHIV management

“…31 The sustained release of NRTIs for long time, enhanced efficacy, and biocompatible nature proposed this NF as a promising candidate to be tested in humanized mouse (hu-PBL) HIV model for the development of personalized nanomedicine. Recent success in the CNS delivery of ARV, ie, zidovudine (AZT), through the nasal route using chitosan microparticles (CP), prepared by spray drying techniques, as a carrier to cure brain HIV sanctuaries has been reported by Dalpiaz et al 32 The authors produced a prodrug via conjugating AZT with ursodeoxycholic acid (UCDA-AZT) to overcome the issue of active efflux transporter systems. The UCDA-AZT (5 µM or 10 µM) system demonstrated 20 times higher efficacy than AZT to cure HIV in the CNS and in macrophages.…”

“…The UCDA-AZT (5 µM or 10 µM) system demonstrated 20 times higher efficacy than AZT to cure HIV in the CNS and in macrophages. 32 To demonstrate delivery to rat brain, the authors administered this prodrugencapsulated CP through the nasal route, aiming to achieve high CNS uptake. The results suggested that utilization of CP increased the dissolution rate of UDCA-AZT and reduced water uptake, resulting in high levels in cerebrospinal fluid in rats, which is required for better efficacy in the CNS.…”

“…The results suggested that utilization of CP increased the dissolution rate of UDCA-AZT and reduced water uptake, resulting in high levels in cerebrospinal fluid in rats, which is required for better efficacy in the CNS. 32 Currently, scientists are exploring novel multi-functional NFs to block unwanted disorders in HIV-infected patients using substance of abuse. 33 Sagar et al 33 developed a highly selective magnetic NF for the delivery of a therapeutic agent to block the effects induced by morphine.…”