PEGylated Lipidic Nanocapsules Encapsulating Olaparib for Breast Cancer Therapy: In Vitro and In Vivo Evaluation

Multifunctional nanoparticles for co-delivery of elacridar and paclitaxel for breast cancer local treatment.

Breast cancer treatment is often limited by toxicity of systemic chemotherapy and by the development of drug resistance, which reduces the effectiveness of anticancer drugs. Delivering therapeutics directly into the mammary ducts has emerged as a promising strategy to increase drug concentrations at the tumor site while limiting unwanted systemic effects. In this study, we assessed two nanoparticle-based systems to locally co-deliver the anticancer drug paclitaxel with elacridar, an inhibitor of drug-efflux transporters that contribute to chemotherapy resistance. One formulation consisted of nanostructured lipid carriers (NLCs), whereas the other was a NLC-polymeric hybrid nanoparticle (H-NP), in which the polymeric poly(N-isopropylacrylamide) shell was functionalized with SILY, a collagen I-binding peptide, to enhance mammary tissue retention. All formulations exhibited diameter below 400  nm, and negative zeta potential (-16.0 to -8.8 mV). Elacridar was incorporated into the lipid matrix of the NLC (>80% encapsulation efficiency) and in the polymeric shell of the H-NPs (∼70%), which justifies its faster release from H-NPs after 120 h (∼92% compared to 75% from NLC). Compared to nanoparticles containing only paclitaxel, co-encapsulation improved cytotoxicity and reduced IC50 (up to 4.2-fold) in monolayers of paclitaxel-resistant MDA-MB-231 breast cancer and Kasumi-1 (characterized by overexpression P-glycoprotein) cells, as well as in MCF-7 3D spheroids. In an in vivo model of breast cancer, intraductal H-NPs reduced tumor incidence and volume compared to a drug solution, and increased the mammary tissue-to-plasma ratio of paclitaxel by 105-fold, supporting an improved tissue retention. These findings support H-NPs as promising platforms for localized breast cancer therapy.

Repurposed Axitinib delivered via lipid-extruded PEGylated liposomes: 2D/3D breast cancer cell evaluation and in-vivo pharmacokinetics.

PEGylated liposomal nanocarriers have emerged as a promising drug delivery platform for improving the pharmacokinetic performance and systemic circulation of poorly water-soluble anticancer drugs. In this study, Axitinib-loaded PEGylated liposomes (F11-PEGliposome) were prepared and evaluated for the potential treatment of breast cancer. Liposomes were prepared by optimization with a Box-Behnken design and subsequently extruded using lipid extrusion to obtain a vesicle size of 158.6 ± 2.4 nm, PDI of 0.12 ± 0.01, zeta potential of -1.2 ± 0.5, and entrapment efficiency of 79.9 ± 1.8%. In 2D cell culture studies, F11-PEGliposome showed enhanced anticancer activity with IC50 values of 1.7- and 2.13-fold lower than free Axitinib. Cellular uptake, ROS generation, JC-1 mitochondrial membrane potential, and AO/EB staining assays exhibited enhanced internalization and apoptosis induction. In 3D spheroid models, F11-PEGliposome exhibited deep penetration in the tumor, significant growth inhibition, increased ROS production, and pronounced apoptotic cell death. In-vivo pharmacokinetic and biodistribution studies showed extended circulation, enhanced bioavailability, and prolonged half-life. Reduced hepatic and renal toxicity was evident as shown by histopathological evaluation and decreased serum AST, ALT, creatinine, and BUN levels. Western blot analysis revealed dose-dependent increases of cleaved caspase-3 and cleaved PARP1, supporting the conclusion of apoptosis.

Liposomes-enabled gemcitabine therapy for breast cancer: in vitro and in vivo studies.

The nasal GLDL spray is anticipated to be a promising and effective treatment option for BC by developing a nasal spray containing GCN-loaded liposomes (GLDL), and exhibited antiproliferative properties, as demonstrated by histopathological analysis of the formulation.

Cationic Lipid Nanoparticles for Co-Encapsulation of Etoposide and Carboplatin: Formulation, Characterization, and In Vitro Evaluation

Engineered Multifunctional Nanococktail of Sorafenib for Targeted Therapy in Hepatic Cancer: In Vivo Study

Design, Development, and Characterization of Carmustine-Loaded Nanostructured Lipid Carriers for Enhanced Brain Accumulation and Antitumor Efficacy in Glioblastoma