Abstract
Effective treatment of glioma still stands as a challenge in medical science. The work aims for the fabrication and evaluation of lipid based nanostructures for improved delivery of lomustine to brain tumor cells. Experimental formulations (LNLs) were developed by modified lipid layer hydration technique and evaluated for different in vitro characteristics like particle size analysis, surface charge, surface morphology, internal structure, in vitro drug loading, drug release profile etc. Anticancer potential of selected LNLs was tested in vitro on C6 glioma cell line. Electron microscopic study depicted a size of less than 50 nm for the selected LNLs along 8.8% drug loading with a sustained drug release tendency over 48 h study period. Confocal microscopy revealed extensive internalization of the selected LNL in C6 cells. LNLs were found more cytotoxic than free drug and blank nanocarriers as depicted from MTT assay. The selected LNL showed improved pharmacokinetic profile both in blood and brain in the experimental mice models along with negligible hemolysis in mice blood cells. Further studies are warranted for the future translation of LNLs at clinics.
Highlights
Effective treatment of brain tumor remains a challenge in medical science
Many conventional anticancer drugs are available in clinical practice, but majority of them fails to maintain the desired therapeutic concentration in the brain tissue for a sufficient period of time due to their inability to pass effectively through blood-brain barrier (BBB).[7]
It is hypothesized that phospholipid based nanostructures may improve the delivery of LS to glioma cells and maintain desired therapeutic concentration in brain tissue over a period of time due to sustained drug release
Summary
Effective treatment of brain tumor remains a challenge in medical science. Gliomas are the most common type of tumors of brain and central nervous system.[1] Based on the type of primary cells along with molecular characteristics, gliomas can be of astrocytomas, ependymomas, oligodendrogliomas etc. Are being claimed to cross BBB, but shorter half-life along with severe dose related toxic effects associated with them throw additional challenges to get desired treatment outcomes.[8,9] In this context, novel drug delivery strategies like nanoliposomes, nanoparticles, polymeric micelles, niosomes, dendrimers etc. Some lipophilic drugs like carmustine, temozolomide, bevacizumab etc. are being claimed to cross BBB, but shorter half-life along with severe dose related toxic effects associated with them throw additional challenges to get desired treatment outcomes.[8,9] In this context, novel drug delivery strategies like nanoliposomes, nanoparticles, polymeric micelles, niosomes, dendrimers etc. have been investigated
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