Design and optimization of olaparib nanostructured lipid carriers for breast cancer treatment

设计和优化用于乳腺癌治疗的奥拉帕尼纳米结构脂质载体

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Abstract

AIMS: Breast cancer (BC) is the most prevalent cancer diagnosed globally. Olaparib (OLA) BCS-IV class drug, is an inhibitor of the poly(ADP-ribose)polymerase enzyme. Due to its restricted absorption, an escalation in dosage and frequency is necessary to attain therapeutic efficacy, which may lead to potential toxicity in patients. In this study, nanostructured lipid carriers (NLCs) were prepared to mitigate OLA's side effects by reducing the dose without compromising efficacy. MATERIALS AND METHODS: OLA-NLCs were formulated, and a Design of Experiments optimization technique was utilized to assess essential formulation parameters systematically. Investigations were conducted on particle size, polydispersity index, zeta potential, encapsulation efficiency, release, and stability assessments. The impact of NLCs was evaluated on MCF-7 and MDA-MB-231 cell lines. RESULTS: OLA-NLCs were evaluated for particle size (134.0 ± 2.56 nm), PDI (0.32 ± 0.01), ZP (-37.7 ± 0.89 mV), and EE (97.28 ± 1.48%). The in-vitro release profile of OLA-NLCs showed a sustained release pattern for 72 h. OLA-NLCs showed a concentration-dependent effect on cell viability for 24 h and 72 h. The uptake of OLA-NLCs was almost 1.75 and 3.69 times higher for MCF-7 and MDA-MB-231, respectively, compared to free-OLA. OLA-NLCs induced more cancer cell apoptosis than free-OLA. CONCLUSIONS: Our data suggest OLA-NLCs may be a practical approach for BC treatment.

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