Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor - Archive ouverte HAL Access content directly
Journal Articles Polymers Year : 2022

Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor

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Amer S Alali
Mohd Abul Kalam
Sulaiman S Alhudaithi
Md Khalid Anwer
Farhat Fatima
  • Function : Author
Muzaffar Iqbal


Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus ®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus ® and mannitol that is indicated by the presence of parent wave number peak. Twofold increased solubility of OLA was found in PBS with Soluplus ® from the NCs (69.3 ± 6.2 µgmL −1) as compared to pure drug (35.6 ± 7.2 µgmL −1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentrationtime profile indicated approximately 2.06-, 2.29-, 2-25-and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 • C, 25 • C and 40 • C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications.
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hal-03884720 , version 1 (05-12-2022)



Amer S Alali, Mohd Abul Kalam, Mohammed Muqtader Ahmed, M Ali Aboudzadeh, Sulaiman S Alhudaithi, et al.. Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor. Polymers, 2022, 14 (22), pp.4827. ⟨10.3390/polym14224827⟩. ⟨hal-03884720⟩
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