Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 213, Issue -, Pages 1115-1126Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.06.031
Keywords
Nose-to-brain drug delivery; Methotrexate; Niosome; In situ gel formulation
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This study introduces a potential niosomal methotrexate (MTX) in situ gel formulation for direct brain drug delivery. By optimizing the preparation method and gel formulation, the study achieved higher brain concentration, lower plasma concentration, and lower side effects.
Achieving effective treatments for various brain disorders due to the blood-brain barrier existence and the brain's complex structure has become a challenging goal. To overcome these challenges, one of the non-invasive strategies aimed at direct brain drug delivery is the use of the intranasal route. Novel drug delivery systems can be used to overcome the limitations in this administration route. This study suggested niosomal methotrexate (MTX) in situ gel formulation, which could be a suitable candidate for drug delivery to the brain. Here, niosomal MTX was prepared by a modified reverse-phase evaporation method, optimized with the aid of the design expert (R) software, and characterized. Optimum niosomal MTX with particle size, zeta potential, and entrapment efficiency (EE%), equal to 130.5 nm,-38.5 mV, and 91.39 %, respectively, were added into the temperature sensitive in situ gel formulation composed of chitosan and Poloxamer 407. This study demonstrates that the simultaneous use of niosome and in situ gel formulations causes long-term persistence in the nasal cavity and helps us to have a more controlled drug release system with higher brain concentration, lower plasma concentration, higher Kp, and lower side effects compared to the free drug (MTX solution), MTX-gel (MTX-loaded in situ gel), and niosomal MTX formulations.
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