Executive Summary : | The postpartum depression (PPD) is a major cause of development of mental disorders in women particularly during the postpartum period with global prevalence of around 100‒150 per 1000 birth. Although, pathophysiology of depression is not well defined however, growing evidence suggests that brain derived neurotrophin factor (BDNF) plays a key role in growth and differentiation of synapses and neurons.Recently, ZULRESSO (brexanolone), a natural allosteric modulator of GABAA is approved for the treatment of PPD. Thus, search of natural therapeutics for the treatment of PPD is need of an hour. This indicated that natural therapeutics with reliable safety profile could be future for the treatment of PPD. We recently found that Ligustilide (Z-ligustilide) can modulate BDNF. Ligustilide (LIG) is a natural phthalide which is the main active metabolite in various Angelica subspecies. Angelica plant is widely used in traditional Chinese medicine (Dong quai) and also utilized in the Himalayan region of India. Our preliminary research indicated that indicated that LIG has poor pharmacokinetics properties which hinder its oral bioavailability and parenteral administration. Our results are supported by preclinical evidences that showed very less oral bioavailability of LIG due to first pass effect . LIG was reported to protect against inflammatory and oxidative stress induced cognitive impairment in preclinical studies, however, due to extremely poor stability and bioavailability in its current form the use of LIG is restricted in many other neurological problems like dementia, vascular dysfunction and inflammatory damages and development of novel formulations of LIG is highly recommended to make it a viable option for testing in clinical trials. Present proposal will formulate an intranasal nose to brain targeting nanoformulation of LIG (bypass the first pass effect) for PPD for the first time and also explore use of an indigenous novel lipid named Chyura butter from Diploknema butyrcea (Rxb.) for the development of nanoformulation. The fat from the tree is used for various household purposes, however it’s potential as a lipid carrier for drug delivery is never explored so far. Therefore, for the first time the Chyura butter will be utilized for drug delivery which might open a new era of a novel indigenous lipid based nanoformulation in future. |