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Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Research Article

Preliminary Studies on Optimization of Anti-Parkinson Drug Loaded Lipid Nanoparticles Enriched Hydrogel Formulations for Management of Parkinson’s Disease

Author(s): Kumara S. Samanthula, Ramesh Alli and Thirupathi Gorre*

Volume 11, Issue 2, 2021

Published on: 11 March, 2021

Page: [112 - 126] Pages: 15

DOI: 10.2174/2468187311666210311114908

Price: $65

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Abstract

Introduction: Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration.

Aim: The objective of the current research was to develop RP-loaded solid lipid nanoparticles (RP- SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that could enhance RP therapeutic outcomes during PD treatment.

Methods: RP nanoparticles were prepared by homogenization followed by probe sonication and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), % assay, % entrapment efficiency, and in vitro release studies. Optimized formulations were converted into hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures.

Results: The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP-loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h. Optimized SLN, NLC, and nanocarrier- loaded hydrogel formulations were stable over three months at 4ºC and 25ºC storage conditions.

Conclusion: Overall, the results demonstrated that lipid nanocarriers and their corresponding hydrogel formulations can be considered as a topical drug delivery vehicle for RP during the treatment of PD.

Keywords: Parkinson's disease, ropinirole, carbopol 934, solid lipid nanoparticles, nanostructured lipid carriers, hydrogel.

Graphical Abstract
[1]
Tysnes O-B, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna) 2017; 124(8): 901-5.
[http://dx.doi.org/10.1007/s00702-017-1686-y] [PMID: 28150045]
[2]
McGregor MM, Nelson AB. Circuit Mechanisms of Parkinson’s Disease. Neuron 2019; 101(6): 1042-56.
[http://dx.doi.org/10.1016/j.neuron.2019.03.004] [PMID: 30897356]
[3]
de Lau LML, Breteler MMB. Epidemiology of Parkinson’s disease. Lancet Neurol 2006; 5(6): 525-35.
[http://dx.doi.org/10.1016/S1474-4422(06)70471-9] [PMID: 16713924]
[4]
Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39(6): 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[5]
Raza C, Anjum R, Shakeel NUA. Parkinson’s disease: Mechanisms, translational models and management strategies. Life Sci 2019; 226: 77-90.
[http://dx.doi.org/10.1016/j.lfs.2019.03.057] [PMID: 30980848]
[6]
Pahwa R, Lyons KE, Hauser RA. Ropinirole therapy for Parkinson’s disease. Expert Rev Neurother 2004; 4(4): 581-8.
[http://dx.doi.org/10.1586/14737175.4.4.581] [PMID: 15853577]
[7]
Shill HA, Stacy M. Update on ropinirole in the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat 2009; 5: 33-6.
[PMID: 19557097]
[8]
Matheson AJ, Spencer CM. Ropinirole: a review of its use in the management of Parkinson’s disease. Drugs 2000; 60(1): 115-37.
[http://dx.doi.org/10.2165/00003495-200060010-00007] [PMID: 10929932]
[9]
Nashatizadeh MM, Lyons KE, Pahwa R. A review of ropinirole prolonged release in Parkinson’s disease. Clin Interv Aging 2009; 4: 179-86.
[PMID: 19503779]
[10]
Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 2004; 3(2): 115-24.
[http://dx.doi.org/10.1038/nrd1304] [PMID: 15040576]
[11]
Wokovich AM, Prodduturi S, Doub WH, Hussain AS, Buhse LF. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. Eur J Pharm Biopharm 2006; 64(1): 1-8.
[http://dx.doi.org/10.1016/j.ejpb.2006.03.009] [PMID: 16797171]
[12]
Benson HA. Transdermal drug delivery: penetration enhancement techniques. Curr Drug Deliv 2005; 2(1): 23-33.
[http://dx.doi.org/10.2174/1567201052772915] [PMID: 16305405]
[13]
Fatima T, Ajjarapu S, Shankar VK, et al. Topical Pilocarpine Formulation for Diagnosis of Cystic Fibrosis. J Pharm Sci 2020; 109(5): 1747-51.
[http://dx.doi.org/10.1016/j.xphs.2020.01.030] [PMID: 32035925]
[14]
Maurya A, Rangappa S, Bae J, Dhawan T, Ajjarapu SS, Murthy SN. Evaluation of soluble fentanyl microneedles for loco-regional anti-nociceptive activity. Int J Pharm 2019; 564: 485-91.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.066] [PMID: 31026490]
[15]
Dudhipala N, Phasha Mohammed R, Adel Ali Youssef A, Banala N. Effect of lipid and edge activator concentration on development of aceclofenac-loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation. Drug Dev Ind Pharm 2020; 46(8): 1334-44.
[http://dx.doi.org/10.1080/03639045.2020.1788069] [PMID: 32598194]
[16]
Tatke A, Dudhipala N, Janga KY, et al. In Situ Gel of Triamcinolone Acetonide-Loaded Solid Lipid Nanoparticles for Improved Topical Ocular Delivery: Tear Kinetics and Ocular Disposition Studies. Nanomaterials (Basel) 2018; 9(1): 33.
[http://dx.doi.org/10.3390/nano9010033] [PMID: 30591688]
[17]
Dudhipala N, Ali Youssef AA, Banala N. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: Comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chem Phys Lipids 2020; 233: 104981.
[http://dx.doi.org/10.1016/j.chemphyslip.2020.104981] [PMID: 33031802]
[18]
Janga KY, Tatke A, Dudhipala N, et al. Gellan Gum Based Sol-to-Gel Transforming System of Natamycin Transfersomes Improves Topical Ocular Delivery. J Pharmacol Exp Ther 2019; 370(3): 814-22.
[http://dx.doi.org/10.1124/jpet.119.256446] [PMID: 30872389]
[19]
Shruthi K, Narendar D, Arjun N, Kishan V. Development and Antimicrobial Evaluation of Binary Ethosomal Topical Gel of Terbinafine Hydrochloride for the Treatment of Onychomycosis. Int J Pharm Sci Res 2018; 11: 9.
[20]
MuÈller RH, MaÈder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery ± a review of the state of the art. Eur J Pharm Biopharm 2000; 17: 161-77.
[21]
Dudhipala N. A comprehensive review on solid lipid nanoparticles as delivery vehicle for enhanced pharmacokinetic and pharmacodynamic activity of poorly soluble drugs. IJPSN 2019; 12: 20.
[22]
Dudhipala N, Ay AA. Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections. Chem Phys Lipids 2020; 232: 104953.
[http://dx.doi.org/10.1016/j.chemphyslip.2020.104953] [PMID: 32814084]
[23]
Dudhipala N, Veerabrahma K. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation. Eur J Pharm Biopharm 2017; 110: 47-57.
[http://dx.doi.org/10.1016/j.ejpb.2016.10.022] [PMID: 27810472]
[24]
Dudhipala N, Veerabrahma K. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Deliv 2016; 23(2): 395-404.
[http://dx.doi.org/10.3109/10717544.2014.914986] [PMID: 24865287]
[25]
Dudhipala N, Puchchakayala G. Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation, cytotoxic, pharmacokinetic, and pathological evaluation. Drug Dev Ind Pharm 2018; 44(10): 1572-82.
[http://dx.doi.org/10.1080/03639045.2018.1445264] [PMID: 29493289]
[26]
Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 2002; 54(Suppl. 1): S131-55.
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720]
[27]
Mei Z, Chen H, Weng T, Yang Y, Yang X. Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm 2003; 56(2): 189-96.
[http://dx.doi.org/10.1016/S0939-6411(03)00067-5] [PMID: 12957632]
[28]
Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao YM. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies. Lipids Health Dis 2009; 8: 6.
[http://dx.doi.org/10.1186/1476-511X-8-6] [PMID: 19243632]
[29]
Narendar D, Thirupathi G. Neuroprotective effect of ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics 2020; 12(5): 448.
[http://dx.doi.org/10.3390/pharmaceutics12050448]
[30]
Fuster J, Negro S, Salama A, et al. HPLC-UV method development and validation for the quantification of ropinirole in new PLGA multiparticulate systems: Microspheres and nanoparticles. Int J Pharm 2015; 491(1-2): 310-7.
[http://dx.doi.org/10.1016/j.ijpharm.2015.06.035] [PMID: 26149934]
[31]
Dudhipala N, Janga KY, Gorre T. Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artif Cells Nanomed Biotechnol 2018; 46(sup2): 616-25.
[http://dx.doi.org/10.1080/21691401.2018.1465068] [PMID: 29688077]
[32]
Dudhipala N, Veerabrahma K. Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Dev Ind Pharm 2015; 41(12): 1968-77.
[http://dx.doi.org/10.3109/03639045.2015.1024685] [PMID: 25830370]
[33]
Gondrala UK, Dudhipala N, Kishan V. Preparation, characterization and in vivo evaluation of felodipine solid-lipid nanoparticles for improved oral bioavailability. 2015; 8: 9.
[34]
Dudhipala N, Janga KY. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm 2017; 43(7): 1205-14.
[http://dx.doi.org/10.1080/03639045.2017.1304957] [PMID: 28274147]
[35]
Thirupathi G, Swetha E, Narendar D. Role of Isradipine Loaded Solid Lipid Nanoparticles on the Pharmacodynamic Effect in Rats. Drug Res (Stuttg) 2017; 67(3): 163-9.
[http://dx.doi.org/10.1055/s-0042-119947] [PMID: 27992936]
[36]
Nagaraj K, Narendar D, Kishan V. Development of olmesartan medoxomil optimized nanosuspension using the Box-Behnken design to improve oral bioavailability. Drug Dev Ind Pharm 2017; 43(7): 1186-96.
[http://dx.doi.org/10.1080/03639045.2017.1304955] [PMID: 28271908]
[37]
Kakkar S, Kaur IP. A novel nanovesicular carrier system to deliver drug topically. Pharm Dev Technol 2013; 18(3): 673-85.
[http://dx.doi.org/10.3109/10837450.2012.685655] [PMID: 22612232]
[38]
Palem CR, Gannu R, Doodipala N, Yamsani VV, Yamsani MR. Transmucosal delivery of domperidone from bilayered buccal patches: in vitro, ex vivo and in vivo characterization. Arch Pharm Res 2011; 34(10): 1701-10.
[http://dx.doi.org/10.1007/s12272-011-1014-2] [PMID: 22076770]
[39]
Reddy AB, Reddy ND. Reddy and Narendar D. Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro dissolution by modified dissolution apparatus, in vivo radiographic studies in human volunteers. Drug Res (Stuttg) 2017; 67(7): 412-8.
[http://dx.doi.org/10.1055/s-0043-102952] [PMID: 28449156]
[40]
Abdellatif AAH, El-Telbany DFA, Zayed G, Al-Sawahli MM. Hydrogel Containing PEG-Coated Fluconazole Nanoparticles with Enhanced Solubility and Antifungal Activity. J Pharm Innov 2019; 14: 112-22.
[http://dx.doi.org/10.1007/s12247-018-9335-z]
[41]
Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual Delivery of Ketoconazole Nanoemulgel for the Effective Management of Onychomycosis. AAPS PharmSciTech 2016; 17(6): 1477-90.
[http://dx.doi.org/10.1208/s12249-016-0488-0] [PMID: 26857516]
[42]
Ramasamy T, Khandasami US, Ruttala H, Shanmugam S. Development of solid lipid nanoparticles enriched hydrogels for topical delivery of anti-fungal agent. Macromol Res 2012; 20: 682-92.
[http://dx.doi.org/10.1007/s13233-012-0107-1]
[43]
Butreddy A, Dudhipala N, Janga KY, Gaddam RP. Lyophilization of small-molecule injectables: an industry perspective on formulation development, process optimization, scale-up challenges, and drug product quality attributes. AAPS PharmSciTech 2020; 21(7): 252.
[http://dx.doi.org/10.1208/s12249-020-01787-w] [PMID: 32885357]
[44]
Vamshi Krishna M, Vijay Kumar B, Narendar Dudhipala. In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-Emulsifying Drug System. Pharm Nanotechnol 2020; 8: 207-24.
[http://dx.doi.org/10.2174/2211738508666200517121637]
[45]
Pitta S, Dudhipala N, Narala A, Veerabrahma K. Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm 2018; 44(3): 484-92.
[http://dx.doi.org/10.1080/03639045.2017.1402918] [PMID: 29124986]
[46]
Arun B, Arjun N, Narendar D. Formulation and characterization of Liquid Crystalline Hydrogel of Agomelatin: In vitro and Ex vivo evaluation. J Appl Pharm Sci 2015; 5(9): 110-4.
[47]
Puglia C, Blasi P, Rizza L, et al. Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation. Int J Pharm 2008; 357(1-2): 295-304.
[http://dx.doi.org/10.1016/j.ijpharm.2008.01.045] [PMID: 18343059]
[48]
Sweeney C, Dudhipala N, Thakkar R, et al. Effect of surfactant concentration and sterilization process on intraocular pressure–lowering activity of Δ9-tetrahydrocannabinolvaline‑hemisuccinate (NB1111) nanoemulsions. Drug Delivery and Translational Research 2020.
[http://dx.doi.org/10.1007/s13346-020-00871-9]
[49]
Soleimanian Y, Goli SAH, Varshosaz J, Sahafi SM. Formulation and characterization of novel nanostructured lipid carriers made from beeswax, propolis wax and pomegranate seed oil. Food Chem 2018; 244: 83-92.
[http://dx.doi.org/10.1016/j.foodchem.2017.10.010] [PMID: 29120809]
[50]
Tirumalesh C, Suram D, Dudhipala N, Banala N. Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharm Nanotechnol 2020; 8(2): 148-60.
[http://dx.doi.org/10.2174/2211738508666200225113359] [PMID: 32096755]
[51]
Youssef A, Dudhipala N, Majumdar S. Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. Pharmaceutics 2020; 12(6): 572.
[http://dx.doi.org/10.3390/pharmaceutics12060572] [PMID: 32575524]
[52]
Freitas C, Müller RH. Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLNTM) dispersions. Int J Pharm 1998; 168: 221-9.
[http://dx.doi.org/10.1016/S0378-5173(98)00092-1]
[53]
Desfrançois C, Auzély R, Texier I. Lipid Nanoparticles and Their Hydrogel Composites for Drug Delivery: A Review. Pharmaceuticals (Basel) 2018; 11(4): 118.
[http://dx.doi.org/10.3390/ph11040118] [PMID: 30388738]
[54]
Müller RH, Alexiev U, Sinambela P, Keck CM. Nanostructured Lipid Carriers (NLC): The Second Generation of Solid Lipid Nanoparticles.Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. 2016; pp. 161-85.
[55]
Suvarna G, Narender D, Kishan V. Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles. IJPSN 2015; 8(1): 2779-85.
[http://dx.doi.org/10.37285/ijpsn.2015.8.1.11]
[56]
Mehnert W, Mäder K. Solid lipid nanoparticles: Production, characterization and applications. Adv Drug Deliv Rev 2012; 64: 83-101.
[http://dx.doi.org/10.1016/j.addr.2012.09.021] [PMID: 11311991]
[57]
Narendar D, Palem CR, Reddy S, Rao YM. Pharmaceutical Development and Clinical Pharmacokinetic Evaluation of Gastroretentive Floating Matrix Tablets of Levofloxacin. IJPSN 2011; 4(3): 1461-7.
[58]
Narendar D, Chinna Reddy P, Sunil R, Madhusudan Rao Y. Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers. Int J Drug Deliv 2012; 4: 462-9.
[59]
Narendar D, Arjun N, Karthik Yadav J, et al. Amoxycillin Trihydrate Floating-Bioadhesive Drug Delivery System for Eradication of Helicobacter pylori: Preparation, In Vitro and Ex Vivo Evaluation. J bioequ avail 2016; 8(3): 118-24.
[60]
Narendar D, Someshwar K, Arjun N, Madhusudan Rao Y. Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral delivery. J Pharm Investig 2016; 46(3): 253-63.
[http://dx.doi.org/10.1007/s40005-016-0232-5]
[61]
Donthi MR, Dudhipala NR, Komalla DR, Suram D, Banala N. Preparation and Evaluation of Fixed Combination of Ketoprofen Enteric Coated and Famotidine Floating Mini Tablets by Single Unit Encapsulation System. J Bioequivalence Bioavailab 2015; 7(6): 279.
[http://dx.doi.org/10.4172/jbb.1000254]
[62]
Alekya T, Narendar D, Mahipal D, Arjun N, Nagaraj B, Narendar D. Arjun N, Mahipal D and Nagaraj B. Design and evaluation of chronomodulated drug delivery of tramadol hydrochloride. Drug Res (Stuttg) 2018; 68(3): 174-80.
[http://dx.doi.org/10.1055/s-0043-119072] [PMID: 28950389]
[63]
Nagaraj B, Anusha K, Narendar D, Sushma P. Formulation and evaluation of microemulsion-based transdermal delivery of duloxetine hydrochloride. IJPSN 2020; 13(1): 4773-82.
[64]
Karri V, Butreddy A, Narender D. Fabrication of Efavirenz Freeze Dried Nanocrystals: Formulation, Physicochemical Characterization, In Vitro and Ex Vivo Evaluation. Adv Sci Eng Med 2015; 7(5): 385-92.
[http://dx.doi.org/10.1166/asem.2015.1710]
[65]
Narendar D, Arjun N, Dinesh S, Karthik J. Biopharmaceutical and Preclinical Studies of Efficient Oral Delivery of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants. IJPSN 2016; 9(1): 3102-11.
[66]
Sandeep V, Narendar D, Arjun N, Kishan V. Lacidipine loaded solid lipid nanoparticles for oral delivery: Preparation, characterization and In vivo evaluation. IJPSN 2016; 9(6): 3524-30.
[http://dx.doi.org/10.37285/ijpsn.2016.9.6.2]
[67]
Banala N, Tirumalesh C, Suram D, Dudhipala N. Zotepine loaded lipid nanoparticles for oral delivery: preparation, characterization, and in vivo pharmacokinetic studies. Fut J Pharm Sci 2020; 6(1): 37.
[http://dx.doi.org/10.1186/s43094-020-00051-z]
[68]
Senapati S, Mehraj T, Dudhipala N, Majumdar S. R12. Preparation and characterization of ligand attached new 8-aminoquinoline derivative loaded nanostructured lipid carriers for liver targeting. Annual Poster Session 2020; 12. https://egrove.olemiss.edu/pharm_annual_posters/12
[69]
Pardeshi CV, Belgamwar VS. Ropinirole-dextran sulfate nanoplex for nasal administration against Parkinson’s disease: in silico molecular modeling and in vitro-ex vivo evaluation. Artif Cells Nanomed Biotechnol 2017; 45(3): 635-48.
[http://dx.doi.org/10.3109/21691401.2016.1167703] [PMID: 27068140]
[70]
Mehraj T, Senapati S, Marathe S, Dudhipala N, Tekwani B, Majumdar S. R21. Preparation, characterization and stability evaluation of ligand anchored primaquine loaded nanostructured lipid carrier systems for liver targeting. Annual Poster Session 2020; 21. https://egrove.olemiss.edu/pharm_annual_posters/21

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