“…Additionally, glibenclamide given intracranioventricularly is rapidly removed across the BBB [16]. Effective nanoformulations of glibenclamide for type 2 diabetes treatment were reported recently [17], but neuroinflammation treatment by CNS-permeable nanoparticles is currently unprecedented. Thus, in this study, dual-ligand liposomes were developed for CNS delivery and the controlled release of glibenclamide, as a model of poorly CNS-bioavailable drugs.…”
Dual functionalized liposomes were developed to cross the blood–brain barrier (BBB) and to release their cargo in a pathological matrix metalloproteinase (MMP)-rich microenvironment. Liposomes were surface-functionalized with a modified peptide deriving from the receptor-binding domain of apolipoprotein E (mApoE), known to promote cargo delivery to the brain across the BBB in vitro and in vivo; and with an MMP-sensitive moiety for an MMP-triggered drug release. Different MMP-sensitive peptides were functionalized at both ends with hydrophobic stearate tails to yield MMP-sensitive lipopeptides (MSLPs), which were assembled into mApoE liposomes. The resulting bi-functional liposomes (i) displayed a < 180 nm diameter with a negative ζ-potential; (ii) were able to cross an in vitro BBB model with an endothelial permeability of 3 ± 1 × 10−5 cm/min; (iii) when exposed to functional MMP2 or 9, efficiently released an encapsulated fluorescein dye; (iv) showed high biocompatibility when tested in neuronal cultures; and (v) when loaded with glibenclamide, a drug candidate with poor aqueous solubility, reduced the release of proinflammatory cytokines from activated microglial cells.
“…Additionally, glibenclamide given intracranioventricularly is rapidly removed across the BBB [16]. Effective nanoformulations of glibenclamide for type 2 diabetes treatment were reported recently [17], but neuroinflammation treatment by CNS-permeable nanoparticles is currently unprecedented. Thus, in this study, dual-ligand liposomes were developed for CNS delivery and the controlled release of glibenclamide, as a model of poorly CNS-bioavailable drugs.…”
Dual functionalized liposomes were developed to cross the blood–brain barrier (BBB) and to release their cargo in a pathological matrix metalloproteinase (MMP)-rich microenvironment. Liposomes were surface-functionalized with a modified peptide deriving from the receptor-binding domain of apolipoprotein E (mApoE), known to promote cargo delivery to the brain across the BBB in vitro and in vivo; and with an MMP-sensitive moiety for an MMP-triggered drug release. Different MMP-sensitive peptides were functionalized at both ends with hydrophobic stearate tails to yield MMP-sensitive lipopeptides (MSLPs), which were assembled into mApoE liposomes. The resulting bi-functional liposomes (i) displayed a < 180 nm diameter with a negative ζ-potential; (ii) were able to cross an in vitro BBB model with an endothelial permeability of 3 ± 1 × 10−5 cm/min; (iii) when exposed to functional MMP2 or 9, efficiently released an encapsulated fluorescein dye; (iv) showed high biocompatibility when tested in neuronal cultures; and (v) when loaded with glibenclamide, a drug candidate with poor aqueous solubility, reduced the release of proinflammatory cytokines from activated microglial cells.
“…The improved absorption of MG in the SLN preparation may be attributed to enhanced lymphatic drug transport. The external lipid-based formulation contributes to increased lymphatic transport by promoting the formation of lipoproteins and intestinal lymphatic lipid flux ( Pandey et al, 2018 , Arrua et al, 2021 ). Fig.…”
“…The rate of GB release from zein nano-particles was faster than that of the pure GB; as after 12 hours, more than 90% of GB was released, while the amount of pure GB dissolved was found to slightly exceed 60%, and needed a period of 24 hours in order to release the whole drug amount. This may be attributed to the enhancement of dissolution of GB after incorporation into zein nanoparticles 71 .…”
Objectives: Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide. According to the statistics declared in 2020 by the World Health Organization [WHO], in the year of 1980, 108 million people have been diagnosed with diabetes mellitus worldwide, then, in 2014, that number had increased to 422 million. In 2020, International Diabetes Federation [IDF] has highlighted that; there will be nearly 700 million adults all over the world to be diagnosed with diabetes by the year of 2045. DM is sub-categorized into Type 1 and Type 2 DM. The former is considered as an autoimmune disorder, in which pancreatic β-cells are destructed, impairing insulin production. While Type 2 DM occurs due to loss of cells sensitivity to insulin. Both are associated with a marked increase in the blood glucose level (BGL) and hence, patients need for pharmacological treatment. T2DM is the most common among diabetic patients and its treatment involves the use of different classes like sulphonylureas, miglitinides and thiazolidinediones. Glibenclamide (GB) belongs to sulphonylureas, its low water solubility accompanied with lower bioavailability demands the use of a higher dose to assure proper management of diabetes. However, this is accompanied in some cases by a severe hypoglycemia that might be lethal in some cases. Therefore, finding a proper delivery system that could improve GB solubility is highly recommended. Nano-medicine could be considered as a promising strategy to improve the solubility and hence, bioavailability of GB. This review is exploring and presenting the recent studies performed to either to encapsulate GB into NPs or reduction of its size to the nano-size level, in order to improve its bioavailability. The review also points to the various obstacles facing nano-medicine clinical application and lack of human studies and sufficient long term safety studies suggesting that future work is needed to make a clearer conclusion about the clinical applicability of the nanodelivery of GB. Methods: This review reports a collection of research articles that investigated the use of several nanodelivery approaches for the delivery of GB up to 2022, using internationally accepted scientific journals and databases. Results: This review shows that the delivery of GB using nano-medicine strategy improves the GB aqueous solubility and hence, improves its oral bioavailability. It also shows that nano-medicine approach could sustain/control the release of GB, therefore, maintaining stable plasma drug concentration and avoiding any undesired fluctuation. Conclusion: The results of the collected articles show that the use of the different nano-medicine categories could be promising to overcome the poor bioavailability of GB. The successful clinical application of the liposomal delivery of certain drugs renders liposomes promising carrier for GB, however, because of the several advantages of the niosomes over liposomes, they seem to be a
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