Abstract

DOI : 10.26650/IstanbulJPharm.2019.19036 Nano drug co-delivery system is a popular strategy for combined application of two or more anticancer and/or synergistic drugs. Synergistic effects of nonsteroidal anti-inflammatory drugs and anti-cancer drugs in cancer treatment are shown in the literature. In this study, it was aimed to screen and understand critical formulation and process parameters inthe preparationflurbiprofen and paclitaxel co-loaded nanoparticles for developing an anti-cancer nano co-delivery system. With this aim, critical parameters were determined using Plackett–Burman experimental design (DoE). Flurbiprofen and paclitaxel drug loading amounts were considered as critical quality attributes to controleffective drug loading ratio. Furthermore, average particle size and zeta potential were also defined as critical quality attributes in order to optimize passive drug targeting and colloidal stability. Surfactant type was determined as the most significant factors for the average particle size and zeta potential. For flurbiprofen and paclitaxel drug loading into the nanoparticles, amounts of both flurbiprofen and paclitaxel were determined as critical factors. Consequently, paclitaxel and flurbiprofen were efficiently loaded into nanoparticles and the impact of the formulation variables were successfully screened by a DoE. By controlling the determined parameters, therapeutic efficacy of co-loaded drug nanoparticles could be maximized in further studies. You may cite this article as : Sahin A, Caban-Toktas S, Tonbul H, Yerlikaya F, Aktas Y, Capan Y (2019). Development of Paclitaxel and Flurbiprofen Co-Loaded PLGA Nanoparticles: Understanding Critical Formulation and Process Parameters Using Plackett–Burman Design. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19036.

Highlights

  • Previous studies showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer drugs, the effects of which were well confirmed in clinical trials ( Thun et al 2002)

  • For flurbiprofen and paclitaxel drug loading into the nanoparticles, amounts of both flurbiprofen and paclitaxel were determined as critical factors

  • Paclitaxel and flurbiprofen were efficiently loaded into nanoparticles, and the impact of the formulation variables was successfully screened by a designs of experiment (DoE)

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Summary

Introduction

Previous studies showed that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer drugs, the effects of which were well confirmed in clinical trials ( Thun et al 2002). Anticancer effects of R-flurbiprofen, a NSAID, have been shown in vitro and in vivo models of prostate and colon cancer (Liu et al 2012). It was demonstrated that R-flurbiprofen increased levels of the tumor suppressor neurotrophin receptor in gastric cancer cells and reversed multidrug resistance (Jin et al 2010). Paclitaxel is one of the most important anticancer drugs, approved by the United States Food and Drug Administration (FDA) for clinical use in chemotherapy. It is a Permeability-glycoprotein (P-gp) substrate (Yerlikaya et al 2013).

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