Poly vinyl pyrrolidone (PVP) based inhaled delivery carriers for olaparib for non-small cell lung cancer (NSCLC) treatment

Non-small cell lung cancer (NSCLC) is ranked first worldwide amongst deadly cancers with poor patient survival rate. While chemotherapy, radiation and surgery are available treatment options, NSCLC tumor cells are known to develop resistance and quickly metastasize. Recently, PARP inhibitors have shown their potential as anti-cancer agents. One of the FDA approved PARP inhibitors, Olaparib (Ola) has been approved for advanced and metastatic ovarian, prostate, pancreatic and breast cancers; and has shown potential in NSCLC treatment. However, due to its low solubility and permeability, Ola possesses poor bioavailability leading to minimal therapeutic efficacy. In this study, we aimed to explore the potential of FDA approved pharmaceutical excipient, Polyvinylpyrrolidone (PVP), as a complexation agent to overcome the challenges of Olaparib by developing an inhaled dosage form for NSCLC treatment.

Phase solubility studies indicated enhanced solubility of Ola when complexed with PVP. Complex formation between Ola and PVP was confirmed via solid state characterization studies. Accelerated stability study showed that Olaparib was not degraded at 37 °C when complexed with PVP, suggesting PVP rendering stability to Olaparib, thus shielding it from harsh environment. The formed Ola-PVP complex demonstrated excellent aerosolization performance and exhibited a higher cytotoxic profile against NSCLC cell lines. 3D tumor simulation studies also depicted improved therapeutic potential of Ola against an actual physiological tumor. This study lays the foundation for preclinical and potential clinical translation of inhaled Olaparib with PVP.

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Materials

Polyvinyl pyrrolidone (Plasdone– K29/32) was obtained as a gift from Ashland (Wilmington, DE, USA). Olaparib (Ola) was purchased from LC Laboratories (Woburn, MA, USA). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO), LC-MS grade water, acetonitrile (ACN), and methanol were purchased from Fisher Scientific (Hampton, NH, USA).

Mimansa Goyal, Gauravi Tulsyan, Dipti D. Kanabar, Tejashri Chavan, Aaron Muth, Vivek Gupta, Poly vinyl pyrrolidone (PVP) based inhaled delivery carriers for olaparib for non-small cell lung cancer (NSCLC) treatment, Journal of Drug Delivery Science and Technology, 2023, 104767, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104767.

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