Phospholipid Based Colloidal Nanocarriers for Enhanced Solubility and Therapeutic Efficacy of Withanolides

Abstract

The bioactive withanolides of Withania somnifera (WS) are reported to treat acute stress-induced anxiety and chronic stress-induced depression. However, its biopharmaceutical attributes such as poor water solubility, poor permeability, and lower bioavailability need to be tuned to improve the therapeutic efficacy. Hence, we hypothesized and designed the present study to enhance withanolides' solubility and therapeutic efficacy by fabricating their naturosomal delivery using phospholipid complexation (PLC). Moreover, investigation of the effect of PLC on solubility and colloidal stability of withanolides encapsulated in naturosomes (WNs) was another objective of the present investigation. Naturosomes were developed and optimized by employing Quality by Design, further characterized for demonstrating their physicochemical and functional properties. The solubility study of WNs exhibited a ∼14-fold and ∼1.3-fold increase in aqueous solubility than the pure WS and physical mixture (PM) with a phospholipid, respectively. The results of dynamic light scattering and zeta potential (−37.30 mV) of WNs has proven its colloidal stability with controlled size particles. These colloidal WNs were transformed in dry powder and retained their stability upon lyophilization. Likewise, the in-vitro dissolution studies exhibited >95% release of withanolides from WNs in comparison with WS (∼27%) or the PM (∼29%). The ex-vivo permeation studies demonstrated significant improvement in the permeation of WNs (>74%) in comparison to the WS (∼16%) or the PM (∼18%). Withanolides encapsulated naturosomes prepared by PLC could be an alternative strategy to enhance the solubility and improve bioavailability and efficacy.