Vol.:(0123456789) 1 3 Journal of Pharmaceutical Investigation https://doi.org/10.1007/s40005-018-00415-x ORIGINAL ARTICLE Natural anti-proliferative agent loaded self-microemulsifying nanoparticles for potential therapy in oral squamous carcinoma Shital C. Patil 1  · Amol A. Tagalpallewar 1  · Chandrakant R. Kokare 1 Received: 29 June 2018 / Accepted: 26 October 2018 © The Korean Society of Pharmaceutical Sciences and Technology 2018 Abstract Piperine is a poorly water-soluble drug and its bioavailability is a great barrier for this drug. The objective of current work was to formulate and investigate a self-microemulsifying drug delivery system (SMEDDS) of piperine as well as modifca- tion of liquid SMEDDS into the solid SMEDDS. Solubility study of piperine was performed in various excipients. Optimum composition of the microemulsion region was identifed by using the pseudo-ternary phase diagram. Liquid SMEDDS for- mulation was optimized by Box–Behnken statistical design. The optimized liquid SMEDDS formulation showed particle size 22.12 ± 0.88 nm, PDI 0.185 ± 0.03 and transmittance 99.48 ± 0.32%. A methyl thiazolyl tetrazolium (MTT) assay was performed to determine in vitro anticancer efcacy of piperine using KB cell lines. The piperine loaded self-microemulsifying nanoparticles signifcantly inhibited the growth of carcinoma cells by targeting mitochondria and produced caspases-3 activ- ity. Whereas, this mechanism showed signifcant role in inhibition of cancer signaling stage. The MTT assay confrmed 98.7% cytotoxicity in cancerous cells. Moreover, PXRD analysis showed the transformation of the crystalline structure of piperine to the amorphous (dissolved) state. In vitro release and ex vivo permeation of liquid and solid-SMEDDS has shown faster drug release as compared to the pure drug. The developed formulation was stable under stability conditions after 3 months of storage. Thus, the studies revealed that SMEDDS has a promising strategy for a poorly water-soluble drug, which benefts to enhance the solubility, dissolution also an anti-proliferative performance of piperine in the oral squamous carcinoma. Keywords Apoptosis · Self-microemulsifying nanoparticles · Solid-SMEDDS · Ex vivo permeation · Piperine Introduction Oral carcinoma is the cancer of neck and head, the preva- lence of squamous carcinoma has been increasing in the many countries. So, the naturally occurring plant drugs, as well as chemotherapeutic chemicals, are necessary to reduce serious malignancy problems (Petersen et al. 2010). The apoptosis activating and inhibiting proliferation of tumor cells might denote an efective approach of natural anticancer agents, which are safe for human use. Conven- tional chemotherapies are toxic to normal healthy tissues and platelets, which cause a harmful efect in patients, but, the herbal drug products are possessing antitumor activity and relatively non-toxic in nature (Amin et al. 2009). Naturally occurring herbal drug products might enhance the safety and efcacy against cancerous cells. Piperine, chemically identifed as 1-piperoyl peperdine, is an alkaloid obtained from the fruits of black pepper (Piper nigrum Linn.). Piperine has been widely used as a traditional medicine. It has many potent pharmacologi- cal and biochemical activities including anti-proliferative, antioxidant, antifungal, anti-infammatory, antimicrobial, immune modulatory and hepato-protective properties. A cytoprotective, as well as chemo preventive results, have been revealed in lung cancer, breast cancer etc. Moreo- ver, these natural products inhibit cancer cell proliferation rate and cellular apoptosis with both intrinsic as well as the extrinsic pathway through activation of caspase-3 and loss of mitochondrial membrane potential (Siddiqui et al. 2017). Since hundreds of years, plants have been showing an extensive source of medicines. Newly, natural therapeu- tic agents with lower solubility, it has advance interest for Online ISSN 2093-6214 Print ISSN 2093-5552 * Chandrakant R. Kokare kokare71@redifmail.com 1 Department of Pharmaceutics, Sinhgad Technical Education Society’s, Sinhgad Institute of Pharmacy (Afliated to Savitribai Phule Pune University), Narhe, Pune, Maharashtra 411041, India