Efavirenz-loaded intranasal microemulsion for crossing blood-CNS interfaces in neuronal-AIDS: pharmacokinetic and in vivo safety evaluation

Abstract

Purpose: Development of delivery tool for the existing antiretroviral drugs against the neuronal-AIDS in itself is a big challenge because of blood-brain-barrier (BBB). Aim of present research is to formulate efavirenz (EFV) based mucoadhesive microemulsion (EMME) and investigates its efficiency through intranasal delivery.

Methods: The EFV microemulsion (EME) was formulated by aqueous titration method. The formulation was screened for globule size, zeta potential and encapsulation efficiency. Bio-distribution of EFV was performed by gamma scintigraphy. Safety of optimized formulation was demonstrated using biochemical, hematological and histopathological data.

Results: Experimental data demonstrate that optimized formulation showed significant size (19.04 nm), zeta potential (−32.2 mV) and entrapment efficiency (98.39%). The results of C_max value suggested that intranasal (i.n.) ^99mTc-EMME is able to improve the brain uptake of EFV around 2 folds more than i.n. ^99mTC-EME and intravenous (i.v.) ^99mTC-EME administrations. The drug targeting index (DTI= 10), drug targeting efficiency (DTE = 1000%) and direct transport percentage (DTP = 89%) were found highly significant for EMME (i.n.) than EME (i.n.). In vivo safety evaluation studies on experimental animals for biochemical, hematological and histopathological parameters remain unchanged.

Conclusions: Hence, the intranasal delivery of EMME can be safe and effective tool in the treatment of neuronal-AIDS.

Keywords:

• Microemulsion
• neuronal-AIDS
• 99mTc radioisotope
• efavirenz
• intranasal delivery

Ethical approval

Experimental animals study protocol was approved by institutional animal ethics committee Protocol No. ACTREC/IAEC/12/2015 and SIOP/IAEC/2017/02/15, as per the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

Acknowledgements

The authors are grateful to ACTREC Kharghar, Navi-Mumbai for support in the gamma scintigraphy study.

Disclosure statement

The authors report no conflict of interest.