Adefovir dipivoxil loaded proliposomal powders with improved hepatoprotective activity: formulation, optimization, pharmacokinetic, and biodistribution studies

Abstract

The present study aimed to prepare proliposomal formulae for improving the oral bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor effective against hepatitis B virus (HBV). The prepared proliposomal formulae were characterized for entrapment efficiency (E.E.%), vesicle size and in vitro drug release after reconstitution to conventional liposomes. The optimized formula (F9) with a maximum desirability value of 0.858 was selected having E.E.% of 71 ± 3.3% with an average vesicle size of 164.6 ± 5 nm. Moreover, the crystallization of AD within the optimized formula investigated via powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) confirmed the presence of the drug in an amorphous state within the lipid vesicles with enhanced stability over a storage period of 12 months. Thioacetamide-induced liver damage in rats evidenced by elevated liver enzymes was significantly improved after treatment with the optimum formula. Pharmacokinetic and biodistribution studies of formula F9 showed a higher accumulation of AD in the liver with enhanced bioavailability compared to AD suspension which highlights its potential advantage for an effective treatment of chronic HBV. Hence, proliposomal drug delivery is considered as a better choice for the oral delivery of AD.

Statistical optimization of bile salt deployed nanovesicles as a potential platform for oral delivery of piperine: accentuated antiviral and anti-inflammatory activity in MERS-CoV challenged mice

“…DSC thermograms of pure piperine, cholesterol, plain lyophilized formula as well as the optimum lyophilized piperineloaded bilosomal formula (F2) were displayed in Figure 6 . DSC thermogram of pure piperine revealed an acute pointed distinctive endotherm at approximately 131.2 °C which is equivalent to its melting point (Ding et al, 2018 ), while cholesterol exhibited an endothemic peak at 148.5 °C corresponding to its melting point (Abdelbary et al, 2018 ). DSC thermogram of lyophilized plain and piperine-loaded bilosomal formula (F2) exhibited no characteristic peak of piperine suggesting the complete transaction of piperine and other components as Brij 72, SDC, and cholesterol from a crystalline to amorphous form proposing good encapsulation of the drug within the vesicles.…”

Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator

“…The formulation of nanoparticulate carrier systems gasp the attention of various scientists in order to enhance the drugs oral bioavailability [6]. Such studies, fabrication of Adefovir dipivoxil proliposomal powders, polymeric nanoparticles and solid lipid nanoparticles that succeeded to improve its bioavailability and biodistribution [5,7].…”

Design, Green Synthesis and Tailoring of Vitamin E TPGS Augmented Niosomal Nano-Carrier of Pyrazolopyrimidines as Potential Anti-Liver and Breast Cancer Agents with Accentuated Oral Bioavailability

“…The adjustment of the equipment was manipulated by adopting purified indium (99.9%). The temperature was elevated at a rate of 10 °C/min, surrounded by nitrogen in a temperature range of 20–400 °C [ 57 ].…”

“…Precisely 1 mL of sorensen phosphate buffer (pH 7.4) was manipulated to disperse with 1 mL of the optimized niosomal formula; then 1 mL, corresponding to 1mg, of the investigated compound from the attained dispersion was placed in a 10 cm in length and 2.5 cm in diameter glass cylinder and a presoaked cellulose membrane was conjugated to its bottom where dispersion prevailed. The shaft of the dissolution tester (Copley, DIS 8000, Nottingham, UK) was then attached to the glass cylinder and located in 900 mL dissolution media (sorensen phosphate buffer, pH 7.4) at 37 ± 0.5 °C and speed of 50 rpm [ 57 ]. At scheduled time interventions, equal volumes were withdrawn from the dissolution media and analyzed by HPLC at 300 nm to compute the percentage of drug released.…”