Development of a Thymoquinone Polymeric Anticancer Nanomedicine through Optimization of Polymer Molecular Weight and Nanoparticle Architecture.

Suhair Sunoqrot,Ala'A M Hammad,Lina Hasan Ibrahim,Malek Alfaraj,Violet Kasabri,Dana Shalabi,Khaldoun Shnewer,Ahmad A Deeb,Ismail Yousef

doi:10.3390/pharmaceutics12090811

Suhair Sunoqrot, Ala'A M Hammad + Show 7 more

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https://doi.org/10.3390/pharmaceutics12090811

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Abstract

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

Highlights

Cancer is considered one of the leading causes of death worldwide and is responsible for millions of deaths annually [1]
Preparation and Characterization of TQ-Loaded NPs with Varying Polymer molecular weight (MW) and NP Architectures methoxy poly(ethylene glycol) (mPEG)-PCL copolymers with two different PCL chain lengths were synthesized in this study by controlling the mPEG:CL weight ratio during synthesis
We showed that NPs based on the biodegradable copolymer mPEG-PCL could be effectively tailored to design a nanoscale delivery system for the bioactive compound TQ

Summary

Introduction

Cancer is considered one of the leading causes of death worldwide and is responsible for millions of deaths annually [1]. Therapeutic success with conventional chemotherapeutic agents is complicated by their notoriously severe side effects, rapid clearance, and tumor relapse due to onset of multidrug resistance [2]. Throughout history, medicinal plants have been used to treat a wide range of diseases Due to their structural diversity, natural products and their derivatives constitute a rich source of bioactive compounds with unique pharmacologic effects against various ailments including cancer [3]. Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone; TQ) is the major constituent of the volatile oil of N. sativa Since it was first isolated, TQ has been investigated for its therapeutic benefits such as antioxidant, anti-inflammatory, anti-diabetic, immunomodulatory, and anticancer effects, in both in vitro and in vivo settings [5]. TQ has been faced with major biopharmaceutical challenges related to its poor aqueous solubility, hindering its therapeutic potential in vivo [6]

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