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Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor
Amer S Alali1, Mohd Abul Kalam2,3, Mohammed Muqtader Ahmed1
1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Polymers
|November 26, 2022
Summary
This study developed nanocrystals of the anticancer drug Olaparib (OLA) to overcome its poor solubility and limited clinical use. The resulting Olaparib nanocrystals (OLA-NCs) showed enhanced solubility, improved anticancer efficacy in cell studies, and significantly increased bioavailability in rats.
Area of Science:
- Pharmaceutical Sciences
- Nanotechnology
- Drug Delivery
Background:
- Olaparib (OLA), a PARP-I inhibitor, is an effective anticancer agent but faces limited clinical application due to its poor solubility and permeability (BCS Class-IV drug).
- Developing advanced drug delivery systems is crucial to enhance the therapeutic performance of poorly soluble drugs like Olaparib.
Purpose of the Study:
- To formulate and characterize Olaparib nanocrystals (OLA-NCs) using Soluplus® as a stabilizer to improve Olaparib's solubility, dissolution, and anticancer efficacy.
- To evaluate the in vitro and in vivo performance of OLA-NCs compared to pure Olaparib.
Main Methods:
- Olaparib nanocrystals (OLA-NCs) were prepared via antisolvent precipitation using homogenization and probe sonication with Soluplus®.
- Particle size, zeta potential, morphology (SEM), drug-excipient interactions (DSC, XRD, FTIR), solubility, in vitro release, and cellular cytotoxicity (MCF-7 cells) were assessed.
- In vivo pharmacokinetic studies in rats and storage stability tests were conducted.
Main Results:
- OLA-NCs exhibited a particle size of ~103 nm with a positive zeta potential (+8.67 mV), indicating good stability.
- Solubility of OLA-NCs in PBS was doubled compared to pure OLA, and in vitro release was significantly higher at pH 6.8.
- OLA-NCs demonstrated enhanced in vitro anticancer activity against MCF-7 cells (lower IC50) and significantly increased expression of p53, Caspase-3, and Caspase-9.
- In vivo studies in rats showed a 2- to 2.6-fold increase in key pharmacokinetic parameters (Cmax, AUC) for OLA-NCs compared to OLA-pure.
- The OLA-NC formulation remained physically and chemically stable for up to 6 months under various storage conditions.
Conclusions:
- The developed Olaparib nanocrystals (OLA-NCs) effectively enhance the solubility, dissolution, and oral bioavailability of Olaparib.
- OLA-NCs show improved in vitro anticancer potency and are a promising formulation strategy to overcome the challenges associated with poorly soluble drugs for potential clinical applications.
