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Recent Advances in Drug Delivery and Formulation

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ISSN (Print): 2667-3878
ISSN (Online): 2667-3886

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Research Article

Ion-activated In Situ Gel of Gellan Gum Containing Chrysin for Nasal Administration in Parkinson’s Disease

Author(s): Khushboo Lavania and Anuj Garg*

Volume 18, Issue 1, 2024

Published on: 06 December, 2023

Page: [35 - 49] Pages: 15

DOI: 10.2174/0126673878279656231204103855

Price: $65

Abstract

Introduction: This study focused on creating an innovative treatment approach for Parkinson's disease (PD), a progressive neurodegenerative condition characterized by the loss of specific neurons in the brain.

Aim: The research aimed to develop a nasal gel using gellan gum containing a complex of chrysin with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the drug’s solubility and stability.

Method: The formulation process involved utilizing central composite design (CCD) to optimize the concentrations of gellan gum and HPMC E5, with viscosity and mucoadhesive strength as key factors. The resulting optimized In Situ gel comprised 0.7% w/v gellan gum and 0.6% w/v HPMC E5, exhibiting desirable viscosity levels for both sol and gel states, along with robust mucoadhesive properties. The formulated gel underwent comprehensive evaluation, including assessments for gelation, drug content, in vitro drug release, ex vivo permeation, and histopathology.

Result: The findings demonstrated superior drug release from the In Situ gel compared to standalone chrysin. Ex vivo studies revealed effective drug permeation through nasal mucosa without causing harm. Moreover, experiments on neuronal cells exposed to oxidative stress (H2O2- induced) showcased significant neuroprotection conferred by chrysin and its formulations. These treatments exhibited notable enhancements in cell viability and reduced instances of apoptosis and necrosis, compared to the control group. The formulations exhibited neuroprotective properties by mitigating oxidative damage through mechanisms, like free radical scavenging and restoration of antioxidant enzyme activity.

Conclusion: In conclusion, this developed In situ gel formulation presents a promising novel nasal delivery system for PD therapy. By addressing challenges related to drug properties and administration route, it holds the potential to enhance treatment outcomes and improve the quality of life for individuals with Parkinson's disease.

« Previous Next »
[1]
DeMaagd G, Philip A. Parkinson’s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P&T 2015; 40(8): 504-32.
[PMID: 26236139]
[2]
Kalia LV, Lang AE. Parkinson’s disease. Lancet 2015; 386(9996): 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[3]
Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 2003; 991(1): 1-14.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07458.x] [PMID: 12846969]
[4]
Goyal A, Verma A, Agrawal N. Dietary phytoestrogens:Neuroprotective role in Parkinson’s disease. Curr Neurovasc Res 2021; 18(2): 254-67.
[http://dx.doi.org/10.2174/1567202618666210604121233] [PMID: 34086550]
[5]
Angelopoulou E, Pyrgelis ES, Piperi C. Neuroprotective potential of chrysin in Parkinson’s disease: Molecular mechanisms and clinical implications. Neurochem Int 2020; 132: 104612.
[http://dx.doi.org/10.1016/j.neuint.2019.104612] [PMID: 31785348]
[6]
Fabbro LD, Goes AR, Jesse CR, et al. Chrysin protects against behavioral, cognitive and neurochemical alterations in a 6-hydroxydopamine model of Parkinson’s disease. Neurosci Lett 2019; 706: 158-63.
[http://dx.doi.org/10.1016/j.neulet.2019.05.036] [PMID: 31121284]
[7]
Murmu A, Krishnamoorthy A, Sevanan M. The flavone chrysin and usage in Parkinson’s disease. In: Martin CR, Patel VB, Preedy VR, Eds. Treatments, Nutraceuticals, Supplements, and Herbal Medicine in Neurological Disorders. Academic Press 2023; pp. 703-17.
[http://dx.doi.org/10.1016/B978-0-323-90052-2.00044-5]
[8]
Mishra A, Mishra PS, Bandopadhyay R, et al. Neuroprotective potential of chrysin: Mechanistic insights and therapeutic potential for neurological disorders. Molecules 2021; 26(21): 6456.
[http://dx.doi.org/10.3390/molecules26216456] [PMID: 34770864]
[9]
Souza LC, Antunes MS, Filho CB, et al. Flavonoid chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain. Pharmacol Biochem Behav 2015; 134: 22-30.
[http://dx.doi.org/10.1016/j.pbb.2015.04.010] [PMID: 25931267]
[10]
Prajit R, Sritawan N, Suwannakot K, et al. Chrysin protects against memory and hippocampal neurogenesis depletion in d-galactose-induced aging in rats. Nutrients 2020; 12(4): 1100.
[http://dx.doi.org/10.3390/nu12041100] [PMID: 32316121]
[11]
Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci 2019; 13: 363.
[http://dx.doi.org/10.3389/fncel.2019.00363] [PMID: 31440144]
[12]
Ahmed MR, Shaikh MA, Ul Haq SHI, Nazir S. Neuroprotective role of chrysin in attenuating loss of dopaminergic neurons and improving motor, learning and memory functions in rats. Int J Health Sci 2018; 12(3): 35-43.
[PMID: 29896070]
[13]
Balakrishnan R, Azam S, Cho DY, Su-Kim I, Choi DK. Natural phytochemicals as novel therapeutic strategies to prevent and treat parkinson’s disease: Current knowledge and future perspectives. Oxid Med Cell Longev 2021; 2021: 1-32.
[http://dx.doi.org/10.1155/2021/6680935] [PMID: 34122727]
[14]
Stompor-Gorący M, Bajek-Bil A, Machaczka M. Chrysin: Perspectives on contemporary status and future possibilities as pro-health agent. Nutrients 2021; 13(6): 2038.
[http://dx.doi.org/10.3390/nu13062038] [PMID: 34198618]
[15]
Fenyvesi F, Nguyen TLP, Haimhoffer Á, et al. Cyclodextrin complexation improves the solubility and caco-2 permeability of chrysin. Materials 2020; 13(16): 3618.
[http://dx.doi.org/10.3390/ma13163618] [PMID: 32824341]
[16]
Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F. Caloric restriction mimetics in nutrition and clinical trials. Front Nutr 2021; 8: 717343.
[http://dx.doi.org/10.3389/fnut.2021.717343] [PMID: 34552954]
[17]
Ge S, Gao S, Yin T, Hu M. Determination of pharmacokinetics of chrysin and its conjugates in wild-type FVB and Bcrp1 knockout mice using a validated LC-MS/MS method. J Agric Food Chem 2015; 63(11): 2902-10.
[http://dx.doi.org/10.1021/jf5056979] [PMID: 25715997]
[18]
Mohos V, Fliszár-Nyúl E, Schilli G, et al. Interaction of chrysin and its main conjugated metabolites chrysin-7-sulfate and chrysin-7-glucuronide with serum albumin. Int J Mol Sci 2018; 19(12): 4073.
[http://dx.doi.org/10.3390/ijms19124073] [PMID: 30562928]
[19]
Dong D, Quan E, Yuan X, Xie Q, Li Z, Wu B. Sodium oleate-based nanoemulsion enhances oral absorption of chrysin through inhibition of UGT-mediated metabolism. Mol Pharm 2017; 14(9): 2864-74.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00851] [PMID: 27983856]
[20]
Ting P, Srinuanchai W, Suttisansanee U, et al. Development of chrysin loaded oil-in-water nanoemulsion for improving bioaccessibility. Foods 2021; 10(8): 1912.
[http://dx.doi.org/10.3390/foods10081912] [PMID: 34441689]
[21]
Anari E, Akbarzadeh A, Zarghami N. Retracted article: Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. Artif Cells Nanomed Biotechnol 2016; 44(6): 1410-6.
[http://dx.doi.org/10.3109/21691401.2015.1029633] [PMID: 26148177]
[22]
Chadha R, Bhalla Y, Nandan A, Chadha K, Karan M. Chrysin cocrystals: Characterization and evaluation. J Pharm Biomed Anal 2017; 134: 361-71.
[http://dx.doi.org/10.1016/j.jpba.2016.10.020] [PMID: 27894779]
[23]
Abbas M. Potential role of nanoparticles in treating the accumulation of amyloid-beta peptide in alzheimer’s patients. Polymers 2021; 13(7): 1051.
[http://dx.doi.org/10.3390/polym13071051] [PMID: 33801619]
[24]
Sharma T, Katare OP, Jain A, et al. QbD-Steered development of biotin-conjugated nanostructured lipid carriers for oral delivery of chrysin: Role of surface modification for improving biopharmaceutical performance. Colloids Surf B Biointerfaces 2021; 197: 111429.
[http://dx.doi.org/10.1016/j.colsurfb.2020.111429] [PMID: 33130524]
[25]
Bahadur S, Sachan N, Harwansh RK, Deshmukh R. Nanoparticlized system: Promising approach for the management of alzheimer’s disease through intranasal delivery. Curr Pharm Des 2020; 26(12): 1331-44. [a]
[http://dx.doi.org/10.2174/1381612826666200311131658] [PMID: 32160843]
[26]
Chapman CD, Frey WH II, Craft S, et al. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res 2013; 30(10): 2475-84.
[http://dx.doi.org/10.1007/s11095-012-0915-1] [PMID: 23135822]
[27]
Bahadur S, Pardhi DM, Rautio J, Rosenholm JM, Pathak K. Intranasal nanoemulsions for direct nose-to-brain delivery of actives for CNS disorders. Pharmaceutics 2020; 12(12): 1230.
[http://dx.doi.org/10.3390/pharmaceutics12121230] [PMID: 33352959]
[28]
Taléns-Visconti R, de Julián-Ortiz JV, Vila-Busó O, Diez-Sales O, Nácher A. Intranasal drug administration in alzheimer-type dementia: Towards clinical applications. Pharmaceutics 2023; 15(5): 1399.
[http://dx.doi.org/10.3390/pharmaceutics15051399] [PMID: 37242641]
[29]
Cunha S, Forbes B, Sousa Lobo JM, Silva AC. Improving drug delivery for alzheimer’s disease through nose-to-brain delivery using nanoemulsions, nanostructured lipid carriers (nlc) and in situ hydrogels. Int J Nanomedicine 2021; 16: 4373-90.
[http://dx.doi.org/10.2147/IJN.S305851] [PMID: 34234432]
[30]
Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: An excellent platform for brain targeting. Expert Opin Drug Deliv 2013; 10(7): 957-72.
[http://dx.doi.org/10.1517/17425247.2013.790887] [PMID: 23586809]
[31]
Khosrow Tayebati S, Ejike Nwankwo I, Amenta F. Intranasal drug delivery to the central nervous system: Present status and future outlook. Curr Pharm Des 2013; 19(3): 510-26.
[http://dx.doi.org/10.2174/138161213804143662] [PMID: 23116337]
[32]
Raj R, Wairkar S, Sridhar V, Gaud R. Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity. Int J Biol Macromol 2018; 109: 27-35.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.056] [PMID: 29247729]
[33]
Bonferoni MC, Rassu G, Gavini E, Sorrenti M, Catenacci L, Giunchedi P. Nose-to-brain delivery of antioxidants as a potential tool for the therapy of neurological diseases. Pharmaceutics 2020; 12(12): 1246.
[http://dx.doi.org/10.3390/pharmaceutics12121246] [PMID: 33371285]
[34]
Saraf S, Alexander A. Nose-to-brain drug delivery approach: A key to easily accessing the brain for the treatment of Alzheimer’s disease. Neural Regen Res 2018; 13(12): 2102-4.
[http://dx.doi.org/10.4103/1673-5374.241458] [PMID: 30323136]
[35]
Rassu G, Soddu E, Cossu M, et al. Solid microparticles based on chitosan or methyl-β-cyclodextrin: A first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate. J Control Release 2015; 201: 68-77.
[http://dx.doi.org/10.1016/j.jconrel.2015.01.025] [PMID: 25620068]
[36]
Ibrahim SS, Abo Elseoud OG, Mohamedy MH, et al. Nose-to-brain delivery of chrysin transfersomal and composite vesicles in doxorubicin-induced cognitive impairment in rats: Insights on formulation, oxidative stress and TLR4/NF-kB/NLRP3 pathways. Neuropharmacology 2021; 197: 108738.
[http://dx.doi.org/10.1016/j.neuropharm.2021.108738] [PMID: 34339751]
[37]
Lungare S, Hallam K, Badhan RKS. Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery. Int J Pharm 2016; 513(1-2): 280-93.
[http://dx.doi.org/10.1016/j.ijpharm.2016.09.042] [PMID: 27633279]
[38]
Tapeinos C, Battaglini M, Ciofani G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release 2017; 264: 306-32.
[http://dx.doi.org/10.1016/j.jconrel.2017.08.033] [PMID: 28844756]
[39]
Türker S, Onur E, Ózer Y. Nasal route and drug delivery systems. Pharm World Sci 2004; 26(3): 137-42.
[http://dx.doi.org/10.1023/B:PHAR.0000026823.82950.ff] [PMID: 15230360]
[40]
Keller LA, Merkel O, Popp A. Intranasal drug delivery: Opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res 2022; 12(4): 735-57.
[http://dx.doi.org/10.1007/s13346-020-00891-5] [PMID: 33491126]
[41]
Nair AB, Chaudhary S, Jacob S, et al. Intranasal administration of dolutegravir-loaded nanoemulsion-based in situ gel for enhanced bioavailability and direct brain targeting. Gels 2023; 9(2): 130.
[http://dx.doi.org/10.3390/gels9020130] [PMID: 36826300]
[42]
Jeswani G, Paul SD. Design of vincristine sulfate loaded poloxamer in situ nanogel: Formulation and in vitro evaluation. J Drug Deliv Sci Technol 2021; 61.
[43]
Vigani B, Rossi S, Sandri G, Bonferoni MC, Caramella CM, Ferrari F. Recent advances in the development of in situ gelling drug delivery systems for non-parenteral administration routes. Pharmaceutics 2020; 12(9): 859.
[http://dx.doi.org/10.3390/pharmaceutics12090859] [PMID: 32927595]
[44]
Ong WY, Shalini SM, Costantino L. Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders. Curr Med Chem 2014; 21(37): 4247-56.
[http://dx.doi.org/10.2174/0929867321666140716103130] [PMID: 25039773]
[45]
Aderibigbe B. In Situ-based gels for nose to brain delivery for the treatment of neurological diseases. Pharmaceutics 2018; 10(2): 40.
[http://dx.doi.org/10.3390/pharmaceutics10020040] [PMID: 29601486]
[46]
Lavania K, Garg A. Inclusion complex of chrysin with hydroxypropyl-β-cyclodextrin (HP-β-CD) preparation, characterization, and dissolution study. Bionanoscience 2023; 13(2): 616-24.
[http://dx.doi.org/10.1007/s12668-023-01106-0]
[47]
Chaturvedi S, Garg A. Development and optimization of nanoemulsion containing exemestane using box-behnken design. J Drug Deliv Sci Technol 2023; 80: 104151.
[http://dx.doi.org/10.1016/j.jddst.2023.104151]
[48]
Srividya B, Cardoza RM, Amin PD. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. J Control Release 2001; 73(2-3): 205-11.
[http://dx.doi.org/10.1016/S0168-3659(01)00279-6] [PMID: 11516498]
[49]
Hassan H, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules 2021; 26(18): 5432.
[http://dx.doi.org/10.3390/molecules26185432] [PMID: 34576904]
[50]
Patro CS, Sahu PK. Combined effect of synthetic and natural polymers in preparation of cetirizine hydrochloride oral disintegrating tablets: optimization by central composite design. J Pharm 2017; 2017: 1-12.
[http://dx.doi.org/10.1155/2017/8305976] [PMID: 28154771]
[51]
Khan S, Patil K, Bobade N, Yeole P, Gaikwad R. Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats. J Drug Target 2010; 18(3): 223-34.
[http://dx.doi.org/10.3109/10611860903386938] [PMID: 20030503]
[52]
Miller SC, Donovan MD. Effect of poloxamer 407 gel on the miotic activity of pilocarpine nitrate in rabbits. Int J Pharm 1982; 12(2-3): 147-52.
[http://dx.doi.org/10.1016/0378-5173(82)90114-4]
[53]
Salunke SR, Patil SB. Ion activated in situ gel of gellan gum containing salbutamol sulphate for nasal administration. Int J Biol Macromol 2016; 87: 41-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.02.044] [PMID: 26899173]
[54]
Corazza E, di Cagno MP, Bauer-Brandl A, et al. Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin. Eur J Pharm Sci 2022; 179: 106294.
[http://dx.doi.org/10.1016/j.ejps.2022.106294] [PMID: 36116696]
[55]
Patil SB, Kaul A, Babbar A, Mathur R, Mishra A, Sawant KK. In vivo evaluation of alginate microspheres of carvedilol for nasal delivery. J Biomed Mater Res B Appl Biomater 2012; 100B(1): 249-55.
[http://dx.doi.org/10.1002/jbm.b.31947] [PMID: 22113887]
[56]
Sunada H, Bi Y. Preparation, evaluation and optimization of rapidly disintegrating tablets. Powder Technol 2002; 122(2-3): 188-98.
[http://dx.doi.org/10.1016/S0032-5910(01)00415-6]
[57]
Pabari RM, Ramtoola Z. Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets. Int J Pharm 2012; 430(1-2): 18-25.
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.021] [PMID: 22465631]
[58]
Donnelly RF, Shaikh R, Raj Singh TR, Garland MJ, Woolfson AD. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci 2011; 3(1): 89-100.
[http://dx.doi.org/10.4103/0975-7406.76478] [PMID: 21430958]
[59]
Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 2009; 71(3): 505-18.
[http://dx.doi.org/10.1016/j.ejpb.2008.09.028] [PMID: 18984051]
[60]
Gohel MC, Parikh RK, Nagori SA, Shah SN, Dabhi MR. Preparation and evaluation of soft gellan gum gel containing paracetamol. Indian J Pharm Sci 2009; 71(2): 120-4.
[http://dx.doi.org/10.4103/0250-474X.54273] [PMID: 20336205]
[61]
Siddhardha B, Pandey U, Kaviyarasu K, et al. Chrysin-loaded chitosan nanoparticles potentiates antibiofilm activity against staphylococcus aureus. Pathogens 2020; 9(2): 115.
[http://dx.doi.org/10.3390/pathogens9020115] [PMID: 32059467]
[62]
Davis SS, Illum L. Absorption enhancers for nasal drug delivery. Clin Pharmacokinet 2003; 42(13): 1107-28.
[http://dx.doi.org/10.2165/00003088-200342130-00003] [PMID: 14531723]
[63]
Jacob S, Nair AB, Boddu SHS, Gorain B, Sreeharsha N, Shah J. An updated overview of the emerging role of patch and film-based buccal delivery systems. Pharmaceutics 2021; 13(8): 1206.
[http://dx.doi.org/10.3390/pharmaceutics13081206] [PMID: 34452167]
[64]
Shukla SK, Chan A, Parvathaneni V, et al. Enhanced solubility, stability, permeation and anti-cancer efficacy of Celastrol-β-cyclodextrin inclusion complex. J Mol Liq 2020; 318: 113936.
[http://dx.doi.org/10.1016/j.molliq.2020.113936]
[65]
Adrover A, di Muzio L, Trilli J, et al. Enhanced loading efficiency and mucoadhesion properties of gellan gum thin films by complexation with hydroxypropyl-β-cyclodextrin. Pharmaceutics 2020; 12(9): 819.
[http://dx.doi.org/10.3390/pharmaceutics12090819] [PMID: 32872207]
[66]
Tie F, Fu Y, Hu N, Wang H. Silibinin protects against H2O2-Induced oxidative damage in SH-SY5Y cells by improving mitochondrial function. Antioxidants 2022; 11(6): 1101.
[http://dx.doi.org/10.3390/antiox11061101]
[67]
Venuprasad MP, Hemanth Kumar K, Khanum F. Neuroprotective effects of hydroalcoholic extract of ocimum sanctum against H2O2 induced neuronal cell damage in SH-SY5Y cells via its antioxidative defence mechanism. Neurochem Res 2013; 38(10): 2190-200.
[http://dx.doi.org/10.1007/s11064-013-1128-7] [PMID: 23996399]
[68]
Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 1995; 9(7): 526-33.
[http://dx.doi.org/10.1096/fasebj.9.7.7737461] [PMID: 7737461]

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