Abstract
Background: Obesity, considered a complex condition, is the fastest-growing public health concern worldwide. Its treatment is limited due to the side effects of pharmacological options available, outweighing their benefits.
Aim: The present study aims to formulate a novel biodegradable formulation of exenatide for direct brain delivery through the nasal route.
Methods: To formulate exenatide loaded poly (lactide-co-glycolide) (PLGA) nanoparticles, a double emulsion (w/o/w) solvent evaporation method was employed. A full factorial (33) design of the experiment was used to optimize the formulation.
Results: The entrapment efficiency and particle size of the optimized formulation were found to be 68% and 110 nm, respectively. The in-vitro drug release study indicated the sustained release of 48% drug in 5 days. The safety of drug-loaded PLGA nanoparticles for intranasal delivery was indicated by the sheep nasal toxicity study. The efficacy of the developed nanoparticles was demonstrated by an in-vivo pharmacodynamics study on Albino Wistar rats, showing a 6.2% weight reduction after 30 days of treatment.
Conclusion: Thus, exenatide is a novel peptide having significant weight loss benefits and no severe side effects. Long-term studies in at least two or more animal models followed by extensive clinical evaluation can safely result in a product for clinical use.
Keywords: Obesity, exenatide, PLGA nanoparticles, double emulsification solvent evaporation, sheep nasal toxicity study, in vivo pharmacodynamic study.
[http://dx.doi.org/10.1097/PRS.0000000000003264] [PMID: 28445378]
[http://dx.doi.org/10.1016/S2213-8587(17)30358-3] [PMID: 29066096]
[http://dx.doi.org/10.1016/S0140-6736(14)60460-8] [PMID: 24880830]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.087213] [PMID: 22753534]
[http://dx.doi.org/10.1093/qjmed/hcx152] [PMID: 29025162]
[PMID: 30167574]
[http://dx.doi.org/10.1016/S1470-2045(14)71123-4] [PMID: 25467404]
[http://dx.doi.org/10.1007/s00268-009-0062-y] [PMID: 19421812]
[http://dx.doi.org/10.15344/2456-8007/2019/131] [PMID: 31058246]
[http://dx.doi.org/10.1684/ecn.2018.0415] [PMID: 30547890]
[http://dx.doi.org/10.1007/s00018-019-03011-w] [PMID: 30683985]
[http://dx.doi.org/10.2174/1570161112666140423223529] [PMID: 24846238]
[http://dx.doi.org/10.1001/jama.2013.281361] [PMID: 24231879]
[http://dx.doi.org/10.4103/2230-8210.176351] [PMID: 27042424]
[http://dx.doi.org/10.1038/oby.2011.50] [PMID: 21415845]
[http://dx.doi.org/10.1016/j.cmet.2018.03.001] [PMID: 29617641]
[http://dx.doi.org/10.1038/s41578-019-0156-6]
[http://dx.doi.org/10.1016/j.brainresbull.2018.10.009] [PMID: 30449731]
[http://dx.doi.org/10.1208/s12248-009-9169-1] [PMID: 20077052]
[http://dx.doi.org/10.3109/10717541003762888] [PMID: 20429846]
[http://dx.doi.org/10.1007/s40005-019-00453-z]
[http://dx.doi.org/10.1016/j.arabjc.2017.05.011]
[http://dx.doi.org/10.1002/pat.3381]
[http://dx.doi.org/10.1002/pat.4375]
[http://dx.doi.org/10.3390/pharmaceutics10040269] [PMID: 30544966]
[http://dx.doi.org/10.1002/jbm.a.36145] [PMID: 28639394]
[http://dx.doi.org/10.1080/02652048.2018.1453560] [PMID: 29542378]
[http://dx.doi.org/10.1371/journal.pone.0049304] [PMID: 23166632]
[http://dx.doi.org/10.1016/j.jconrel.2007.09.013] [PMID: 18083265]
[http://dx.doi.org/10.1016/j.jconrel.2008.09.073] [PMID: 18848962]
[http://dx.doi.org/10.1080/02652040400026442] [PMID: 16019905]
[http://dx.doi.org/10.1016/j.ijpharm.2007.11.012] [PMID: 18162341]
[http://dx.doi.org/10.1089/adt.2019.920] [PMID: 31184962]
[http://dx.doi.org/10.1016/j.actbio.2011.07.025] [PMID: 21839863]
[http://dx.doi.org/10.1208/s12249-009-9329-8] [PMID: 19894122]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01245.x] [PMID: 21265828]
[http://dx.doi.org/10.1080/02652048.2017.1375038] [PMID: 28862072]
[http://dx.doi.org/10.3109/03639045.2014.938081] [PMID: 25026246]
[http://dx.doi.org/10.1016/j.msec.2017.03.121] [PMID: 28482569]
[http://dx.doi.org/10.1016/j.carbpol.2008.11.010]
[http://dx.doi.org/10.1016/j.msec.2015.10.003] [PMID: 26652355]
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2013006475] [PMID: 23614648]
[http://dx.doi.org/10.1208/s12249-019-1474-0] [PMID: 31399890]
[http://dx.doi.org/10.1016/j.ijpharm.2013.04.084] [PMID: 23684658]
[http://dx.doi.org/10.1080/10717544.2016.1223216] [PMID: 27648847]
[http://dx.doi.org/10.5455/jice.20160623122710] [PMID: 27757271]
[http://dx.doi.org/10.1007/s42452-021-04609-1]
[http://dx.doi.org/10.1080/21691401.2021.1939709] [PMID: 34151674]
[http://dx.doi.org/10.1248/cpb.58.1474] [PMID: 21048339]
[http://dx.doi.org/10.1016/j.ajps.2019.01.002] [PMID: 32636952]
[http://dx.doi.org/10.3390/ph13110335] [PMID: 33114120]