Fabrication and evaluation of carbocisteine-loaded solid lipid nanoparticles to treat pulmonary infections

Authors

  • Bhushan R. Rane Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206
  • Ashish S. Jain Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206
  • Nikita P. Mane Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206
  • Vaibhav Patil Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206
  • Mukesh S. Patil Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206
  • Kedar R. Bavaskar Department of Pharmaceutics, Shri D. D. Vispute College of Pharmacy & Research Center, Panvel, Dist. Raigad, India 410206

DOI:

https://doi.org/10.69857/joapr.v12i6.661

Keywords:

Carbocisteine, Solid Lipid Nanoparticle, Particle Size, Stability, Zeta Potential

Abstract

Background:  Solid lipids Nanoparticles (SLN) comprise physiological and biocompatible lipids. SLN is an alternative carrier system to polymeric nanoparticles or liposomes. It has been claimed that SLN offers combined advantages and avoids the disadvantages of other colloidal carrier systems. Aim: The research aims to fabricate and evaluate the carbocisteine solid lipid nanoparticles loaded in situ gel. Methodology:  SLN was prepared by using glycerol monostearate as a solid lipid and by high-pressure homogenization (Panda plus 2000) method using poloxamer 188 as a stabilizer to improve its bioavailability and reduce particle size. The quality-by-design concept was used to develop the SLN by optimizing process variables. Result and discussion: The drug and excipient compatibility study was checked using FTIR, and no interaction between both was found. Optimized SLN of carbocisteine were evaluated for zeta potential, particle size, and % drug release, found results as -19.67 mv, 50 to 200 nm, and up to 70.84%, respectively. Optimized gel batches were also evaluated for the stability study. Conclusion: All the batches were evaluated for various parameters. The F6 batch was optimized based on particle size, stability, Zeta potential, and release pattern. SLN could provide a better advantage of good penetration and targeting to treat pulmonary disease.

Downloads

Download data is not yet available.

References

Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK. Solid lipid nanoparticles: a review on recent perspectives and patents. Expert Opin Ther Pat, 30(3), 179-94 (2020) https://doi.org/10.1080/13543776.2020.1720649.

Costa CP, Barreiro S, Moreira JN, Silva R, Almeida H, Sousa Lobo JM, Silva AC. In vitro studies on nasal formulations of nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN). Pharmaceuticals, 14(8),711 (2021) https://doi.org/10.3390/ph14080711.

Bhagwat GS, Athawale RB, Gude RP, Md S, Alhakamy NA, Fahmy UA, Kesharwani P. Formulation and development of transferrin targeted solid lipid nanoparticles for breast cancer therapy. Front Pharmacol, 27(11), 614290 (2020) https://doi.org/10.3389/fphar.2020.614290.

Pandian SR, Pavadai P, Vellaisamy S, Ravishankar V, Palanisamy P, Sundar LM, Chandramohan V, Sankaranarayanan M, Panneerselvam T, Kunjiappan S. Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor. Naunyn Schmiedebergs Arch Pharmacol, 394,735-49 (2021) https://doi.org/10.1007/s00210-020-02015-9.

Sakellari GI, Zafeiri I, Batchelor H, Spyropoulos F. Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active. Food Hydrocoll Health, 1(1),100024 (2021) https://doi.org/10.1016/j.fhfh.2021.100024.

Shah P, Chavda K, Vyas B, Patel S. Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: role of P-gp inhibition. Drug Deliv Transl Res, 11, 1166-85 (2021) https://doi.org/10.1007/s13346-020-00839-9.

Hassan H, Adam SK, Alias E, Meor Mohd Affandi MM, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 26(18), 5432 (2021) https://doi.org/10.3390/molecules26185432.

Mura P, Maestrelli F, D’Ambrosio M, Luceri C, Cirri M. Evaluation and comparison of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as vectors to develop hydrochlorothiazide effective and safe pediatric oral liquid formulations. Pharmaceutics, 13(4), 437 (2021) https://doi.org/10.3390/pharmaceutics13040437.

Naseri M, Golmohamadzadeh S, Arouiee H, Jaafari MR, Nemati SH. Preparation and comparison of various formulations of solid lipid nanoparticles (SLNs) containing essential oil of Zataria multiflora. Jour of Hor and Posth Res, 3(1),73-84 (2020) https://doi.org/10.22077/jhpr.2019.2570.1068.

Mendoza-Munoz N, Urbán-Morlán Z, Leyva-Gómez G, de la Luz Zambrano-Zaragoza M, Quintanar-Guerrero D. Solid lipid nanoparticles: an approach to improve oral drug delivery. J Pharm Pharm Sci, 13(24), 509-32 (2021) https://doi.org/10.18433/jpps31788.

Godge G, Randhawan B, Shaikh A, Bharat S, Raskar M, Hiremath S. Formulation Perspectives and Applications of Solid Lipid Nanoparticles for Drug Delivery: A Review. RGUHS Jour of Pharm Sci,14(1), (2024) https://doi.org/10.26463/rjps.14_1_7.

Scioli Montoto S, Muraca G, Ruiz ME. Solid lipid nanoparticles for drug delivery: pharmacological and biopharmaceutical aspects. Front Mol Biosci, 30(7), 319 (2020) https://doi.org/10.3389/fmolb.2020.587997.

Mirchandani Y, Patravale VB, Brijesh S. Solid lipid nanoparticles for hydrophilic drugs. J Control Release. 10(335), 457-64 (2021) https://doi.org/10.1016/j.jconrel.2021.05.032.

Satapathy MK, Yen TL, Jan JS, Tang RD, Wang JY, Taliyan R, Yang CH. Solid lipid nanoparticles (SLNs): an advanced drug delivery system targeting brain through BBB. Pharmaceutics, 13(8),1183 (2021) https://doi.org/10.3390/pharmaceutics13081183.

Gupta T, Singh J, Kaur S, Sandhu S, Singh G, Kaur IP. Enhancing bioavailability and stability of curcumin using solid lipid nanoparticles CLEN): A covenant for its effectiveness. Front Bioeng Biotechnol, 15(8), 879 (2020) https://doi.org/10.3389/fbioe.2020.00879.

Liparulo A, Esposito R, Santonocito D, Muñoz-Ramírez A, Spaziano G, Bruno F, Xiao J, Puglia C, Filosa R, Berrino L, D'Agostino B. Formulation and Characterization of Solid Lipid Nanoparticles Loading RF22-c, a Potent and Selective 5-LO Inhibitor, in a Monocrotaline-Induced Model of Pulmonary Hypertension. Front pharmacol, 28(11), 83 (2020) https://doi.org/10.3389/fphar.2020.00083.

Musielak E, Feliczak-Guzik A, Nowak I. Optimization of the conditions of solid lipid nanoparticles (SLN) synthesis. Molecules, 27(7), 2202 (2022) https://doi.org/10.3390/molecules27072202.

E, Cerveri I, Lacedonia D, Paone G, Sanduzzi Zamparelli A, Sorbo R, Allegretti M, Lanata L, Scaglione F. Clinical efficacy of carbocysteine in COPD: beyond the mucolytic action. Pharmaceutics, 14(6),1261 (2022) https://doi.org/10.3390/pharmaceutics14061261.

Fu Y, Dai A, Dong L, Ning K. Efficacy and Safety of Expectorant/antioxidants in the Treatment of COPD: Network Meta-analysis. China Pharmacy, 2778-84 (2021) https://pesquisa.bvsalud.org/portal/resource/pt/wpr-904783.

Ferraro M, Di Vincenzo S, Sangiorgi C, Leto Barone S, Gangemi S, Lanata L, Pace E. Carbocysteine modifies circulating miR-21, IL-8, sRAGE, and fAGEs levels in mild acute exacerbated COPD patients: a pilot study. Pharmaceuticals, 15(2), 218 (2022) https://doi.org/10.3390/ph15020218.

Zhou L, Liu J, Wang L, He Y, Zhang J. Carbocistein improves airway remodeling in asthmatic mice. Am J Transl Res, 14(8), 5583 (2022) https://pmc.ncbi.nlm.nih.gov/articles/PMC9452364/.

Rubio MC, de la Serna Blazquez O, Martin JL, Cuetos MR. Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis. Opn Jou Res Dis, 14(2), 39-50 (2024) https://doi.org/10.4236/ojrd.2024.142004.

Dailah HG. Therapeutic potential of small molecules targeting oxidative stress in the treatment of chronic obstructive pulmonary disease (COPD): a comprehensive review. Molecules, 27(17), 5542 (2022) https://doi.org/10.3390/molecules27175542.

Kariya S, Okano M, Higaki T, Makihara S, Tachibana T, Nishizaki K. Long-term treatment with clarithromycin and carbocisteine improves lung function in chronic cough patients with chronic rhinosinusitis. Am J Otolaryngol, 41(1), 102315 (2020) https://doi.org/10.1016/j.amjoto.2019.102315.

Lo Bello F, Ieni A, Hansbro PM, Ruggeri P, Di Stefano A, Nucera F, Coppolino I, Monaco F, Tuccari G, Adcock IM, Caramori G. Role of the mucins in pathogenesis of COPD: implications for therapy. Expert Rev Respir Med, 14(5), 465-83 (2020) https://doi.org/10.1080/17476348.2020.1739525.

Abdelhamid AM, Youssef ME, Cavalu S, Mostafa-Hedeab G, Youssef A, Elazab ST, Ibrahim S, Allam S, Elgharabawy RM, El-Ahwany E, Amin NA. Carbocisteine as a modulator of Nrf2/HO-1 and NFκB interplay in rats: new inspiration for the revival of an old drug for treating ulcerative colitis. Front Pharmacol, 8(13), 887233 (2022) https://doi.org/10.3389/fphar.2022.887233.

Bhalekar MR, Madgulkar AR, Desale PS, Marium G. Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug Dev Ind Pharm, 43(6), 1003–10 (2017) https://doi.org/10.1080/03639045.2017.1291666.

Rubiano S, Echeverri JD, Salamanca CH. Solid lipid nanoparticles (SLNs) with potential as cosmetic hair formulations made from Otoba wax and ultrahigh pressure homogenization. Cosmetics, 7(2), 42 (2020) https://doi.org/10.3390/cosmetics7020042.

Steiner D, Bunjes H. Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation. Int J Pharm, 1(3), 100085 (2021) https://doi.org/10.1016/j.ijpx.2021.100085.

Kraisit P, Hirun N, Mahadlek J, Limmatvapirat S. Fluconazole-loaded solid lipid nanoparticles (SLNs) as a potential carrier for buccal drug delivery of oral candidiasis treatment using the Box-Behnken design. J Drug Deliv Sci Technol, 1(63), 102437 (2021) https://doi.org/10.1016/j.jddst.2021.102437.

Khan S, Ullah M, Saeed S, Saleh E, Kassem A, Arbi F, Wahab A, Rehman M, ur Rehman K, Khan D, Zaman U. Nanotherapeutic approaches for transdermal drug delivery systems and their biomedical applications. Eur Polym J, 6(2), 112819 (2024) https://doi.org/10.1016/j.eurpolymj.2024.112819.

Jai Bharti Sharma, Bhatt S, Tiwari A, Tiwari V, Kumar M, Verma R, et al. Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus. Saudi Pharm J, 31(9), 101727–7 (2023) https://doi.org/10.1016/j.jsps.2023.101727.

Taherzadeh S, Naeimifar A, Yeganeh EM, Esmaili Z, Mahjoub R, Javar HA. Preparation, statistical optimization and characterization of propolis-loaded solid lipid nanoparticles using Box-Behnken design. Adv Pharm Bull, 11(2), 301 (2021) https://doi.org/10.34172/apb.2021.043.

Devi AR, Vidyavathi M, Suryateja SP. Surface modification of optimized asenapine maleate loaded solid lipid nanoparticles using box-behnken design. J. Pharm. Res. Int, 15(33), 176-93 (2021) https://doi.org/10.9734/jpri/2021/v33i31B31706.

Singh S, Dobhal AK, Jain A, Pandit JK, Chakraborty S. Formulation and Evaluation of Solid Lipid Nanoparticles of a Water Soluble Drug: Zidovudine. Chem Pharm Bull, 58(5), 650–5 (2010) https://doi.org/10.1248/cpb.58.650.

Mura P, Maestrelli F, D’Ambrosio M, Luceri C, Cirri M. Evaluation and comparison of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as vectors to develop hydrochlorothiazide effective and safe pediatric oral liquid formulations. Pharmaceutics, 3(4), 437 (2021) https://doi.org/10.3390/pharmaceutics13040437.

Khoiriyah M, Perangirangin JM, Kuncahyo I. Fenofibrate Characterization of Solid Lipid Nanoparticles Using the High Shear Homogenization Method. Nat Sci Eng Tech J, 2(2), 79-86 (2022) https://doi.org/10.37275/nasetjournal.v2i2.21.

Chandana M, Ramana MV, Rao NR. Formulation and evaluation of Valsartan solid lipid nanoparticles. J Drug Deliv Sci Technol, 25(11), (2-S),103-8 (2021) https://doi.org/10.22270/jddt.v11i2-S.4694.

Nasiri F, Faghfouri L, Hamidi M. Preparation, optimization, and in-vitro characterization of α-tocopherol-loaded solid lipid nanoparticles (SLNs). Drug Dev Ind Pharm, 46(1), 159-71 (2020) https://doi.org/10.1080/03639045.2019.1711388.

Butani S. Fabrication of an ion-sensitive in situ gel loaded with nanostructured lipid carrier for nose to brain delivery of donepezil. A Jour Pharm, 12(04), (2018) https://doi.org/10.22377/ajp.v12i04.2838.

Yu S, Wang QM, Wang X, Liu D, Zhang W, Ye T, Yang X, Pan W. Liposome incorporated ion sensitive in situ gels for opthalmic delivery of timolol maleate. Int J Pharm, 480(1-2),128-36 (2015) https://doi.org/10.1016/j.ijpharm.2015.01.032.

Huang CH, Hu PY, Wu QY, Xia MY, Zhang WL, Lei ZQ, Li DX, Zhang GS, Feng JF. Preparation, in vitro and in vivo Evaluation of Thermosensitive in situ Gel Loaded with Ibuprofen-Solid Lipid Nanoparticles for Rectal Delivery. Drug Des Devel Ther, 31, 1407-31 (2023) https://doi.org/10.2147/DDDT.S350886.

Tatke A, Dudhipala N, Janga KY, Balguri SP, Avula B, Jablonski MM, Majumdar S. In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: tear kinetics and ocular disposition studies. Nanomaterials, 9(1), 33, (2018) https://doi.org/10.3390/nano9010033.

Janga KY, Tatke A, Balguri SP, Lamichanne SP, Ibrahim MM, Maria DN, Jablonski MM, Majumdar S. Ion-sensitive in situ hydrogels of natamycin bilosomes for enhanced and prolonged ocular pharmacotherapy: in vitro permeability, cytotoxicity and in vivo evaluation. Artif Cells Nanomed Biotechnol, 31, 46 (sup1), 1039-50 (2018) https://doi.org/10.1080/21691401.2018.1443117.

Lynch CR. Development and characterization of a solid lipid nanoparticle-loaded thermosensitive gel for the delivery of timolol to the eye (Doctoral dissertation, Department of Ophthalmology, Faculty of Health Sciences, University of the Witwatersrand, South Africa) https://hdl.handle.net/10539/34840.

Okur NÜ, Yağcılar AP, Siafaka PI. Promising polymeric drug carriers for local delivery: the case of in situ gels. Curr Drug Deliv, 17(8), 675-93 (2020) https://doi.org/10.2174/1567201817666200608145748.

Uppuluri CT, Ravi PR, Dalvi AV. Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease. Int J Pharm, 606, 120881 (2021) https://doi.org/10.1016/j.ijpharm.2021.120881.

Sun K, Hu K. Preparation and characterization of tacrolimus-loaded SLNs in situ gel for ocular drug delivery for the treatment of immune conjunctivitis. Drug Des Devel Ther, 12, 141 (2021) https://doi.org/10.2147/DDDT.S287721.

Sun Y, Li L, Xie H, Wang Y, Gao S, Zhang L, Bo F, Yang S, Feng A. Primary studies on construction and evaluation of ion-sensitive in situ gel loaded with paeonol-solid lipid nanoparticles for intranasal drug delivery. Int J Nanomedicine, 4, 3137-60 (2020) https://doi.org/10.2147/IJN.S247935.

Amkar AJ, Rane BR, Jain AS. Development and Evaluation of Nanosuspension Loaded Nanogel of Nortriptyline HCl for Brain Delivery. Eng Proc, 56(1), 58 (2023) https://doi.org/10.3390/ASEC2023-15311.

Elkarray SM, Farid RM, Abd-Alhaseeb MM, Omran GA, Habib DA. Intranasal repaglinide-solid lipid nanoparticles integrated in situ gel outperform conventional oral route in hypoglycemic activity. J Drug Deliv Sci Technol, 68, 103086 (2022) https://doi.org/10.1016/j.jddst.2021.103086.

Das T, Venkatesh MP, Kumar TP, Koland M. SLN based alendronate in situ gel as an implantable drug delivery system–A full factorial design approach. J Drug Deliv Sci Technol, 55, 101415 (2020) https://doi.org/10.1016/j.jddst.2019.101415.

Ahmed TA, Badr-Eldin SM, Ahmed OA, Aldawsari H. Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin. J Drug Deliv Sci Technol, 1(48), 499-508 (2018) https://doi.org/10.1016/j.jddst.2018.10.027.

Mohanty D, Alsaidan OA, Zafar A, Dodle T, Gupta JK, Yasir M, Mohanty A, Khalid M. Development of atomoxetine-loaded NLC in situ gel for nose-to-brain delivery: optimization, in vitro, and preclinical evaluation. Pharmaceutics, 15(7), 1985 (2023) https://doi.org/10.3390/pharmaceutics15071985.

Abbas H, Refai H, El Sayed N. Superparamagnetic iron oxide–loaded lipid nanocarriers incorporated in thermosensitive in situ gel for magnetic brain targeting of clonazepam. J Pharm Sci , 107(8), 2119-27 (2018) https://doi.org/10.1016/j.xphs.2018.04.007.

Gade S, Patel KK, Gupta C, Anjum MM, Deepika D, Agrawal AK, Singh S. An ex vivo evaluation of moxifloxacin nanostructured lipid carrier enriched in situ gel for transcorneal permeation on goat cornea. J Pharm Sci, 108(9), 2905-16 (2019) https://doi.org/10.1016/j.xphs.2019.04.005.

Bondre RM, Kanojiya PS, Wadetwar RN, Kangali PS. Sustained vaginal delivery of in situ gel containing Voriconazole nanostructured lipid carrier: formulation, in vitro and ex vivo evaluation. J Dispers Sci Technol, 44(8), 1466-78 (2023) https://doi.org/10.1080/01932691.2021.2022489.

Tripathi D, Sonar PK, Parashar P, Chaudhary SK, Upadhyay S, Saraf SK. Augmented brain delivery of cinnarizine through nanostructured lipid carriers loaded in situ gel: in vitro and pharmacokinetic evaluation. BioNanoScience, 11(1), 159-71 (2021) https://doi.org/10.1007/s12668-020-00821-2.

Li JC, Zhang WJ, Zhu JX, Zhu N, Zhang HM, Wang X, Zhang J, Wang QQ. Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia. Int J clin exp med, 8(10), 17590 (2015) https://pubmed.ncbi.nlm.nih.gov/26770349/.

Chen P, Zhang H, Cheng S, Zhai G, Shen C. Development of curcumin loaded nanostructured lipid carrier based thermosensitive in situ gel for dermal delivery. Colloids Surf A Physicochem Eng Asp, 5, 506, 356-62 (2016) https://doi.org/10.1016/j.colsurfa.2016.06.054.

Aboud HM, El Komy MH, Ali AA, El Menshawe SF, Abd Elbary A. Development, optimization, and evaluation of carvedilol-loaded solid lipid nanoparticles for intranasal drug delivery. AAPS pharmscitech, 17, 1353-65 (2016) https://doi.org/10.1208/s12249-015-0440-8.

Rajput AP, Butani SB. Resveratrol anchored nanostructured lipid carrier loaded in situ gel via nasal route: Formulation, optimization and in vivo characterization. J Drug Deliv Sci Technol, 51, 214-23 (2019) https://doi.org/10.1016/j.jddst.2019.01.040.

Abdelbary A, Salem HF, Khallaf RA, Ali AM. Mucoadhesive niosomal in situ gel for ocular tissue targeting: in vitro and in vivo evaluation of lomefloxacin hydrochloride. Pharm Dev Technol, 22(3), 409-17 (2017) https://doi.org/10.1080/10837450.2016.1219916.

Wavikar PR, Vavia PR. Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery. J Liposome Res, 25(2), 141-9 (2015) https://doi.org/10.3109/08982104.2014.954129.

Mahmoud RA, Hussein AK, Nasef GA, Mansour HF. Oxiconazole nitrate solid lipid nanoparticles: formulation, in-vitro characterization and clinical assessment of an analogous loaded carbopol gel. Drug Dev Ind Pharm, 46(5), 706-16 (2020) https://doi.org/10.1080/03639045.2020.1752707.

Published

2024-12-31

How to Cite

Rane, B. R. ., Jain, A. S. ., Mane, N. P., Patil, V., Patil, M. S. ., & Bavaskar, K. R. . (2024). Fabrication and evaluation of carbocisteine-loaded solid lipid nanoparticles to treat pulmonary infections. Journal of Applied Pharmaceutical Research, 12(6), 122-136. https://doi.org/10.69857/joapr.v12i6.661

Issue

Section

Articles