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

Autor: Mohamed Y. Zakaria, Eman Fayad, Islam Zaki, Fayez Althobaiti, Ali H. Abu Almaaty
Jazyk: angličtina
Rok vydání: 2021
Předmět:
inflammatory cytokines
Pharmaceutical Science
Administration
Oral
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
chemistry.chemical_compound
Mice
0302 clinical medicine
Drug Delivery Systems
Piperidines
Aqueous solubility
Cytochrome P-450 Enzyme Inhibitors
media_common
Liposome
General Medicine
021001 nanoscience & nanotechnology
Molecular Docking Simulation
Piperine
Middle East Respiratory Syndrome Coronavirus
0210 nano-technology
optimization
Research Article
Drug
2019-20 coronavirus outbreak
medicine.drug_class
Polyunsaturated Alkamides
media_common.quotation_subject
Biological Availability
RM1-950
Antiviral Agents
Anti-inflammatory
pharmacokinetic study
Proinflammatory cytokine
Bile Acids and Salts
03 medical and health sciences
Surface-Active Agents
anti-MERS-CoV activity
Alkaloids
medicine
Animals
Piperine bilosomes
Benzodioxoles
Plants
Medicinal
molecular docking
Bioavailability
Nanostructures
Drug Liberation
chemistry
Liposomes
Therapeutics. Pharmacology
Zdroj: Drug Delivery
article-version (VoR) Version of Record
Drug Delivery, Vol 28, Iss 1, Pp 1150-1165 (2021)
ISSN: 1521-0464
1071-7544
Popis: The objective of this paper is to confine piperine, a poor oral bioavailable herbal drug into bile salt based nano vesicles for improving its aqueous solubility, hence, its therapeutic activity. Piperine-loaded bilosomes were fabricated adopting thin film hydration technique according to 32.21 full factorial design to investigate the impact of different formulation variables on the characters of bilosomes: entrapment efficiency (EE%), particle size, and % of drug released post 8 h (Q8hr). The selected optimum formula was F2 (enclosing 1% bile salt, brij72 as a surfactant, and ratio of surfactant:cholesterol was 9:1) with desirability value 0.801, exhibiting high EE% (97.2 ± 0.8%) nanosized spherical vesicles (220.2 ± 20.5 nm) and Q8hr (88.2%±5.6). The superiority of the optimized formula (F2) over the drug suspension was revealed via ex vivo permeation study, also pharmacokinetic study denoted to the boosted oral bioavailability of piperine-loaded bilosome compared to piperine suspension. Moreover, antiviral activity and safety margin of F2 was significantly higher than that of the drug suspension. The ability of piperine to interact with the key amino acids in the receptor binding domain 4L3N as indicated by its docking configuration, rationalized its observed activity. Furthermore, F2 significantly reduce oxidant markers, inflammatory cytokines in MERS-CoV-infected mice. Hence, bilosomes can be considered as a carrier of choice for piperine with potential antiviral and anti-inflammatory activities.
Databáze: OpenAIRE
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