Abstract
Purpose The current investigation is on the explicit development and evaluation of nanostructured lipidic carriers (NLCs) through the oral route to overcome the inherent lacuna of chemotherapeutic drug, in which Ribociclib (RBO) was used for breast cancer to diminish the bioavailability issue. Method The RBO-NLCs were prepared using the solvent evaporation method and optimized method by the Box–Behnken design (BBD). Various assessment parameters characterized the optimized formulation and their in vivo study. Results The prepared NLCs exhibited mean particle size of 114.23 ± 2.75 nm, mean polydispersity index of 0.649 ± 0.043, and high entrapment efficiency of 87.7 ± 1.79%. The structural analysis by TEM revealed the spherical size of NLCs and uniform drug distribution. An in vitro drug release study was established through the 0.1 N HCl pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8 with % cumulative drug release of 86.71 ± 8.14, 85.82 ± 4.58, and 70.98 ± 5.69%, was found respectively, compared with the RBO suspension (RBO-SUS). In vitro intestinal gut permeation studies unveiled a 1.95-fold gain in gut permeation by RBO-NLCs compared with RBO-SUS. In vitro lipolysis suggests the drug availability at the absorption site. In vitro haemolysis study suggests the compatibility of NLCs to red blood cells compared to the suspension of the pure drug. The confocal study revealed the depth of penetration of the drug into the intestine by RBO-NLCs which was enhanced compared to RBO-SUS. A cell line study was done in MCF-7 and significantly reduced the IC50 value compared to the pure drug. The in vivo parameters suggested the enhanced bioavailability by 3.54 times of RBO-NLCs as compared to RBO-SUS. Conclusion The in vitro, ex vivo, and in vivo results showed a prominent potential for bioavailability enhancement of RBO and effective breast cancer therapy.
Highlights
The incidence of cancerous disease recently increased in recent years, impacting the physical, mental, and social life of humans
The in vitro drug release from the nanostructured lipidic carriers (NLCs) nanoformulation shows a sustained release for a long time, unlike drug suspension, which is only up to 24 h of drug release, and it could not maintain the sustained drug release for a longer period
The in vitro haemolysis study suggested that the NLCs formulation of the given drug was safe compared to the pure drug
Summary
The incidence of cancerous disease recently increased in recent years, impacting the physical, mental, and social life of humans. The estimate showed that more than 7 million people die from cancer disease and is predicted to be 10 to 15 million new cases added by 2020. This disease is an unexceptional malignant breast cancer found in women, with more than 1 million fresh cases added yearly [1]. The mechanism of action of RBO is to hamper the activity of cyclin-dependent kinase (CDK) at different types of cyclins like CDK4 and CDK6 of cell cycle pathways which indirectly inhibit the retinoblastoma (Rb) protein phosphorylation.
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