RESUMEN
BACKGROUND: Withania somnifera is a medicinal plant native to India and is known to have anticancer properties. It has been investigated for its anti-melanoma properties, and since melanoma presents on the skin, it is prudent to probe the use of W. somnifera in topical formulations. To enhance topical drug delivery and to allow for controlled release, the use of niosomes and solid lipid nanoparticles (SLNs) as delivery vesicles were explored. OBJECTIVE: The objective of this study is to determine the stability and topical delivery of W. somnifera crude extracts encapsulated in niosomes and SLNs. MATERIALS AND METHODS: Water, ethanol, and 50% ethanol crude extracts of W. somnifera were prepared using 24 h soxhlet extraction which were each encapsulated in niosomes and SLNs. Franz cell diffusion studies were conducted with the encapsulated extracts to determine the release and skin penetration of the phytomolecules, withaferin A, and withanolide A. RESULTS: The niosome and SLN formulations had average sizes ranging from 165.9 ± 9.4 to 304.6 ± 52.4 nm with the 50% ethanol extract formulations having the largest size. A small particle size seemed to have correlated with a low encapsulation efficiency (EE) of withaferin A, but a high EE of withanolide A. There was a significant difference (P < 0.05) between the amount of withaferin A and withanolide A that were released from each of the formulations, but only the SLN formulations managed to deliver withaferin A to the stratum corneum-epidermis and epidermis-dermis layers of the skin. CONCLUSION: SLNs and niosomes were able to encapsulate crude extracts of W. somnifera and release the marker compounds, withaferin A, and withanolide A, for delivery to certain layers in the skin. SUMMARY: Withania somnifera crude extracts were prepared using ethanol, water, and 50% ethanol as solvents. These three extracts were then incorporated into niosomes and solid lipid nanoparticles (SLNs) for use in skin diffusion studies, thus resulting in six formulations (ethanol niosome, water niosome, 50% ethanol niosome, ethanol SLN, water SLN, and 50% ethanol SLN). The diffusion of two marker compounds (withaferin A and withanolide A) from the formulations into the skin was then determined. Abbreviations used: API: Active pharmaceutical ingredient, ANOVA: Analysis of variance, ED: Epidermis-dermis, HPLC: High-performance liquid chromatography, HLB: Hydrophilic-lipophilic balance, NMR: Nuclear magnetic resonance spectroscopy, PDI: Polydispersity index, SLN: Solid lipid nanoparticle, SD: Standard deviation, SCE: Stratum corneum-epidermis, TEM: Transmission electron microscopy.
RESUMEN
The blood-brain barrier is formed by the brain capillary endothelium and plays the predominant role in controlling the passage of substances between the blood and the brain. Recent studies on polycyclic structures, i.e. pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane and amantadine, indicated favourable distribution thereof to the brain and it was concluded that these polycyclic structures and their derivatives penetrate the blood-brain barrier readily. A series of novel polycyclic prodrugs incorporating the well known non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and ibuprofen, were synthesised and screened for blood-brain barrier permeability and antioxidant activity. Increased levels of both NSAIDs were detected in the brain tissue of C57BL/6 mice after administration of the synthesised prodrugs, indicating favourable blood-brain barrier permeation. Results from a lipid peroxidation assay indicated that the ester and amide prodrugs significantly increased the ability of the drugs to attenuate lipid peroxidation. These novel prodrugs thus readily penetrate the blood-brain barrier and exhibit increased antioxidant activity when compared to the free NSAIDs.