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 Cmax 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.
Subject(s)
Acquired Immunodeficiency Syndrome/metabolism , Benzoxazines/pharmacokinetics , Central Nervous System/metabolism , Emulsions/pharmacokinetics , Nasal Mucosa/metabolism , Neurons/metabolism , Administration, Intranasal/methods , Alkynes , Animals , Blood-Brain Barrier/metabolism , Cyclopropanes , Drug Delivery Systems/methods , Male , Rats , Rats, Wistar , Tissue DistributionABSTRACT
Bone healing of tibial defect in rabbit model was used to evaluate a composite coating of apatite-wollastonite/chitosan on titanium implant. This coating has been developed to overcome the shortcomings, such as implant loosening and lack of adherence, of uncoated titanium implant. An electrophoretic deposition technique was used to coat apatite-wollastonite/chitosan on titanium implants. The present study was designed to evaluate the bone response of coated as compared to uncoated titanium implants in an animal model. After an implantation period of 14 (group A), 21 (group B), 35 (group C) and 42 days (group D), the bone-implant interfaces and defect site healing was evaluated using radiography, scintigraphy, histopathology, fluorescence labeling and haematology. Radiography of defect sites treated with coated implants suggested expedited healing. Scintigraphy of coated implant sites indicated faster bone metabolism than uncoated implant sites. Histopathological examination and fluorescence labeling of bone from coated implant sites revealed higher osteoblastic activity and faster mineralization. Faster bone healing in the case of coated implant sites is attributed to higher cell adhesion on electrostatically charged chitosan surfaces and apatite-wollastonite-assisted mineralization at bone-implant interfaces. Haematological studies showed no significant differences in haemoglobin, total erythrocyte and leukocyte counts, done using one way-ANOVA, during the entire study period. Our results show that AW/chitosan-coated implants have the advantages of faster bone healing, increased mechanical strength and good bone-implant bonding.
