Brain targeted intra nasal acyclovir lipid nanoparticles; in-vitro characterization and in-vivo biodistribution studies

Acyclovir (ACY) is an antiviral class of drugs used to treat herpes simplex virus infections such as herpes simplex encephalitis (HSE). ACY is widely distributed; Systemic exposure of ACY leads to serious adverse effects. Because of its high pH, intravenous ACY may cause phlebitis and local inflammation if extravasation occurs. This study aims to enhance acyclovir delivery to the brain via the intranasal route by formulating ACY nano lipid carriers (ACY- NLCs) to circumvent the side-effects, as mentioned earlier. ACY-NLCs were prepared by emulsification, followed by ultrasonication. A Box-Behnken statistical design with three factors, three levels and 17 runs was selected for the optimization study using Design-Expert Software. Nanoparticles were characterized for particle size, entrapment efficiency and in-vitro drug release. ACY-NLC showed biphasic release pattern i.e. an initial faster release followed by sustained release. Biodistribution study by imaging, Nanoparticles were slowly cleared and biodistributed to the other organs was observed in 2nd and 3rd hr post-administration. From the toxicity studies, NLC formulation is safe and non- toxic for the nasal administration. Rhodamine loaeded NLCs were quickly adsorbed by the olfactory tract and distributed mainly to the lungs through respiratory tract and were also detected in the trachea and olfactory bulb. Biodistribution study of dye loaded NLCs reach brain compared to the Rhodamine-solution. Keywords: Acyclovir, blood-brain barrier, blood-cerebrospinal fluid barrier, central nervous system, intranasal, nano lipid carriers.