Photolytic Controlled Release Formulation of Methotrexate Loaded in Chitosan/TiO2 Nanoparticles for Breast Cancer

Abstract

A new system composed of chitosan nanoparticles loaded with methotrexate (MTX-CS-NPs) and functionalized with photocatalytic TiO2 nanoparticles (TiO2-NPs) was prepared. This system is expected to initiate polymeric rupture of MTX-CS-NPs and subsequently release MTX, upon illumination with UV light. MTX-CS-NPs were prepared and characterized in terms of particle size, charge, polydispersity and drug release before and after coating with TiO2-NPs. The release of MTX in vitro was studied in dark, light and UV light. Finally, coated and uncoated MTX-CS-NPs were studied in vitro using MCF-7 cell line. The functionalized NPs were larger in size, more polydisperse and carried higher positive charges compared to the unfunctionalized NPs. The entrapment efficacy was high reaching 75% and was not affected by coating with MTX-CS-NPs. Further, less than 5% of methotrexate was released after 80 h from uncoated NPs and the release was not enhanced by UV illumination of the particles. In contrast, the release from functionalized NPs was enhanced, reaching 40% after 80 h, as the particles were stroked with UV light and as the amount of TiO2-NPs used in coating increased. Finally, coating the MTX-CS-NPs with TiO2-NPs significantly enhanced their cytotoxicity on MCF-7 cells. The coated MTX-CS-NPs recorded low cell viabilities compared to the other formulations. In conclusion, the drug release of MTX-CS-NPs could be triggered and controlled remotely by coating with TiO2-NPs, which maybe more effective in cancer treatment.

Surface-Decorated Nanocarrier as a Targeted Drug Delivery Cargo to Folate Receptor-Overexpressing Cells for Enhancing Anti-cancer and Anti-inflammatory Activity

“…Collectively, such mechanisms could synergistically enhance the cytotoxicity and antitumor effect of FA-CS coated MTX NPs. Interestingly, the majority of studies using MTXloaded NPs focus on breast cancer cells [11,22,29]. Our findings on HeLa cells could support recent findings reported in the literature that MTX could be used to treat cervical cancer in a clinical setting [82].…”

“…The dialysis bag diffusion method was equipped to evaluate the in vitro release pattern of MTX from the optimized freshly prepared uncoated formulation (F2) and either 0.1% or 0.2% FA-CS coated formulation F10 and F11, respectively, and to compare their release patterns with that of free MTX as control from each release medium [17,22,29]. The experiment was held at three different pH values (1.2, 6.8, and 7.4).…”

Magnetic and pH-Responsive Magnetite/Chitosan (Core/Shell) Nanoparticles for Dual-Targeted Methotrexate Delivery in Cancer Therapy

“…1c) clearly illustrated the embedding of iron oxide nuclei within the polymeric matrices. The observed clustering of NPs was likely a consequence of the sample preparation method involving drying for microscopy observations, a phenomenon documented in existing literature [38,49,63]. EDX analyses further validated the NP composition, verifying the presence of Fe, C, N and O elements within the NPs (Fig.…”

“…Several MTX-loaded CS-based NPs have been designed to enhance controlled drug delivery to tumors [46][47][48][49]. These include actively targeted NPs, such as those using covalently conjugated to folate [48], as well as stimuli-responsive particles.…”

Nanocarriers for methotrexate delivery/codelivery in the frame of cancer diagnostics and treatment: a review

“…CS NPs without TiO 2 NPs coating did not release a significant percentage of a drug upon UV irradiation, whereas TiO 2 NPs improved the release of MTX up to 40% in the presence of UV light. The cytotoxicity data confirmed that the developed nanosystem was cytotoxic against MCF-7 cells, hence showing promise in cancer therapy (Al-Nemrawi et al, 2022). In order to pass through the blood-brain barrier (BBB), which is as physical/biochemical barrier, the transactivator of transcription (TAT) peptide was used to produce mesoporous silica nanoparticles-linked TAT (MSN-NH-TAT) with the aim of improving MTX (MTX-loaded MSN-NH-TAT) penetration into the brain.…”