Thermosensitive hydrogel for in situ-controlled methotrexate delivery

Abstract

Methotrexate (MTX) is widely used for the treatment of various types of cancer; however, it has drawbacks such as low solubility, lack of selectivity, premature degradation, and side effects. To solve these weaknesses, a hydrogel with the ability to contain and release MTX under physiological conditions without burst release was synthesized. The hydrogel was fabricated with a poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL–PEG–PCL) triblock copolymer, synthesized by ring-opening polymerization. The characterizations by proton nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectrometry confirmed the copolymer assembly, whereas the molecular weight analysis validated the PCL2000–PEG1000–PCL2000 structure. The copolymer aqueous solution exhibited sol–gel phase transition at 37°C and injection capacity. The hydrogel supported a load of 1,000 μg MTX·mL−1, showing a gradual and sustained release profile of the drug for 14 days, with a delivery up to 92% at pH 6.7. The cytotoxicity of the MTX-loaded hydrogel was performed by the methyl thiazole tetrazolium assay, showing a mean inhibitory concentration of 50% of MCF-7 cells (IC50) at 43 µg MTX·mL−1.

Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects

“…Poloxamers such as poloxamer 407, 188, and 388 are made of only one poly(propylene oxide) group and two hydrophilic blocks [46]; thus, the loading of hydrophobic chemotherapeutics into poloxamer-based hydrogels is therefore severely limited. For example, Carrillo-Castillo and colleagues prepared a thermoresponsive PCL-PEG-PCL triblock copolymer which loaded only 1 ug/mL of methotrexate with no significant improvement to the drug's aqueous solubility [47]. Insoluble drugs may also become heterogeneously distributed within the hydrogels, leading to variabilities and non-uniformity of drug release rates from hydrogel samples.…”

“…Figure 3 depicts the sol-gel transition and drug loading of diblock and triblock copolymers. Attempts to improve this deficiency in amphiphilic thermosensitive hydrogels have been explored by combining block copolymers of differing molecular weights and ratios [47], including complexes such as cyclodextrins (CD) [48] or synthesising dual delivery systems such as the use of nanocarriers and liposomes, with targets for thermoresponsive sol-gel properties [49][50][51]. One study maximised this hybrid strategy by loading nanocrystals into a thermosensitive hydrogel constructed with poloxamer 407, poloxamer 188, and carbomer 974P to generate PTX-nanocrystalline gel [52].…”

Synthesis and Characterization of Polymer-Based Membranes for Methotrexate Drug Delivery

“…Since alginate is an anionic polysaccharide [8], the present study aimed to characterize and compare pharmaceutical formulations for the release of methotrexate based on another anionic polysaccharide, namely κ-carrageenan [9], or a cationic polysaccharide, namely chitosan [10]. Other research groups have published studies on the release of methotrexate, e.g., through hydrogels [11] or magnetic nanoparticles [12].…”

“…Since alginate is an anionic polysacchae and compare pharmaceutical formulaother anionic polysaccharide, namely κely chitosan [10]. Other research groups trexate, e.g., through hydrogels [11] or e name carrageenan, which are obtained olieriaceae, Hypneaceae, and Furcellariaceea lic colloids that can be classified into six rigin, and solubility: kappa (κ-), iota (ɩ-), (θ-) carrageenan. From a chemical point pyranose structure in which part of the [13][14][15].…”

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery

“…to non-parenteral (such as topical, oral, etc.) [ 6 ]. Currently, hydrogels are an attractive type of site-specific drug delivery system, and have many applications in medical and biomedical engineering, including wound and cartilage regeneration, bone tissue engineering, soft robotic components, biosensors, and inflammation relief [ 7 , 8 ].…”