Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting.

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer.

Crosslinked and PEGylated Pectin Chitosan nanoparticles for delivery of Phytic acid to colon.

Polysaccharide-based nanoparticles (NPs) such as pectin/ chitosan (PN/CN) had always been of greatest interest because of their excellent solubility, biocompatibility, and higher suitability for oral drug delivery. This study employed blending-crosslinking of polymers (PN&CN) followed by emulsification-solvent evaporation to prepare and compare two sets of PEGylated NPs to deliver phytic acid (IP6) to colon orally as it has potential to manage colon cancer but fails to reach colon when ingested in pure form. The first set was crosslinked with Glutaraldehyde (GE) (GE*PN-CN-NPs) while the second set was crosslinked with sodium tripolyphosphate (TPP) (TPP*PN-CN-NPs). IP6-loaded-GE/TPP*PN-CN-NPs were optimized using a central composite design. Developed TPP*PN-CN-NPs had a smaller size (210.6 ± 7.93 nm) than GE*PN-CN-NPs (557.2 ± 5.027 nm). Prepared NPs showed <12% IP6 release at pH 1.2 whereas >80% release was observed at pH 7.4. Further, NPs were explored for cytocompatibility in J774.2 cell lines, cytotoxicity, and cellular uptake in HT-29 and DLD-1 cell lines. While exhibiting substantial cytotoxicity and cellular uptake in HT-29 and DLD-1, the NPs were deemedsafe in J774.2. The PEGylated-TPP*PN-CN-NPs showed time-dependent uptake in J774.2 cell lines. Conclusively, the employed NP development method successfully delivered IP6 to colon and may also open avenues for the oral delivery of other drugs to colon.