BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS
DOI:
https://doi.org/10.22159/ijap.2021v13i3.40668Keywords:
Lipid-polymer hybrid nanoparticles, Curcumin, Topical gels, Psoriasis, ImiquimodAbstract
Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis.
Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin-loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)-induced psoriasis rat model.
Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm2/h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels.
Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis.
Downloads
References
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Identification and management of psoriasis and associated comorbidity (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 2013;133:377-85.
Alexis AF, Blackcloud P. Psoriasis in skin of color: epidemiology, genetics, clinical presentation, and treatment nuances. J Clin Aesthet Dermatol 2014;7:16-24.
Moorchung N, Khullar J, Mani N, Chatterjee M, Vasudevan B, Tripathi T. A study of various histopathological features and their relevance in the pathogenesis of psoriasis. Indian J Dermatol 2013;58:294-8.
Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci 2019;20:1475-502.
Zeng J, Luo S, Huang Y, Lu Q. Critical role of environmental factors in the pathogenesis of psoriasis. J Dermatol 2017;44:863-72.
Su YH, Fang JY. Drug delivery and formulations for the topical treatment of psoriasis. Expert Opin Drug Delivery 2008;5:235-49.
Wolf R, Orion E, Ruocco E, Ruocco V. Abnormal epidermal barrier in the pathogenesis of psoriasis. Clin Dermatol 2012;30:323-8.
Fereig SA, El-Zaafarany GM, Arafa MG, Abdel-Mottaleb MMA. Tackling the various classes of nano-therapeutics employed in topical therapy of psoriasis. Drug Delivery 2020;27:662-80.
Zhang Z, Tsai PC, Ramezanli T, Michniak Kohn BB. Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2013;5:205-18.
Hua S. Lipid-based nano-delivery systems for skin delivery of drugs and bioactives. Front Pharmacol 2015;6:1-5.
Niska K, Zielinska E, Radomski MW, Inkielewicz Stepniak I. Metal nanoparticles in dermatology and cosmetology: interactions with human skin cells. Chem Biol Interact 2018;1:38-51.
Zhang Y, Wu M, Wu M, Zhu J, Zhang X. Multifunctional carbon-based nanomaterials: applications in biomolecular imaging and therapy. ACS Omega 2018;3:9126-45.
Carter P, Narasimhan B, Wang Q. Biocompatible nanoparticles and vesicular systems in transdermal drug delivery for various skin diseases. Int J Pharm 2019;555:49-62.
Rahman M, Akhter S, Ahmad J, Ahmad MZ, Beg S, Ahmad FJ. Nanomedicine-based drug targeting for psoriasis: potentials and emerging trends in nanoscale pharmacotherapy. Expert Opin Drug Delivery 2015;12:635-52.
Gupta S, Bansal R, Gupta S, Jindal N, Jindal A. Nanocarriers and nanoparticles for skin care and dermatological treatments. Indian Dermatol Online J 2013;4:267-72.
Tahir N, Madni A, Balasubramanian V, Rehman M, Correia A, Kashif PM, et al. Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications. Int J Pharm 2017;533:156-68.
Zhang L, Chan JM, Gu FX, Rhee JW, Wang AZ, Radovic Moreno AF, et al. Self-assembled lipid-polymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano 2008;2:1696-702.
Hadinoto K, Sundaresan A, Cheow WS. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review. Eur J Pharm Biopharm 2013;85:427-43.
Mbese Z, Khwaza V, Aderibigbe BA. Curcumin and its derivatives as potential therapeutic agents in prostate, colon and breast cancers. Molecules 2019;24:4386-409.
Kamel AE, Fadel M, Louis D. Curcumin-loaded nanostructured lipid carriers prepared using Peceol™ and olive oil in photodynamic therapy: development and application in breast cancer cell line. Int J Nanomed 2019;14:5073-85.
Kotagale NR, Charde PB, Helonde A, Gupta KR, Umekar MJ, Raut NS. Studies on bioavailability enhancement of curcumin. Int J Pharm Pharm Sci 2020;12:20-5.
Gajra B, Dalwadi C, Patel R. Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using box behnken design. Daru 2015;23:3-17.
Bose RJ, Arai Y, Ahn JC, Park H, Lee SH. Influence of cationic lipid concentration on properties of lipid-polymer hybrid nanospheres for gene delivery. Int J Nanomed 2015;10:5367-82.
Massadeh S, Omer ME, Alterawi A, Ali R, Alanazi FH, Almutairi F, et al. Optimized polyethylene glycolylated polymer-lipid hybrid nanoparticles as a potential breast cancer treatment. Pharmaceutics 2020;12:666-79.
Jain A, Thakur K, Kush P, Jain UK. Docetaxel loaded chitosan nanoparticles: formulation, characterization and cytotoxicity studies. Int J Biol Macromol 2014;69:546-53.
Thadakapally R, Aafreen A, Aukunuru J, Habibuddin M, Jogala S. Preparation and characterization of PEG-albumin-curcumin nanoparticles intended to treat breast cancer. Indian J Pharm Sci 2016;78:65-72.
Govindaraju R, Karki R, Chandrashekarappa J, Santhanam M, Shankar A, Joshi HK, et al. Enhanced water dispersibility of curcumin encapsulated in alginate-polysorbate 80 nanoparticles and bioavailability in healthy human volunteers. Pharm Nanotechnol 2019;7:39-56.
Khan MA, Zafaryab M, Mehdi SH, Ahmad I, Rizvi MM. Characterization and anti-proliferative activity of curcumin loaded chitosan nanoparticles in cervical cancer. Int J Biol Macromol 2016;93:242-53.
Alizadeh N, Malakzadeh S. Antioxidant, antibacterial and anti-cancer activities of β-and γ-CDs/curcumin loaded in chitosan nanoparticles. Int J Biol Macromol 2020;147:778-91.
Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, et al. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol 2010;79:330-8.
Kumar SS, Mahesh A, Mahadevan S, Mandal AB. Synthesis and characterization of curcumin loaded polymer/lipid based nanoparticles and evaluation of their antitumor effects on MCF-7 cells. Biochim Biophys Acta 2014;1840:1913-22.
Behbahani ES, Ghaedi M, Abbaspour M, Rostamizadeh K. Optimization and characterization of ultrasound assisted preparation of curcumin-loaded solid lipid nanoparticles: application of central composite design, thermal analysis and X-ray diffraction techniques. Ultrason Sonochem 2017;38:271-80.
Dash S, Murthy PN, Nath LK, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67:217-23.
Dave V, Sharma S, Yadav RB, Agarwal U. Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis. Appl Nanosci 2017;7:973-87.
Xu H, Wen Y, Chen S, Zhu L, Feng R, Song Z. Paclitaxel skin delivery by micelles-embedded Carbopol 940 hydrogel for local therapy of melanoma. Int J Pharm 2020;587:1-11.
Bhalekar MR, Pokharkar V, Madgulkar A, Patil N, Patil N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery. AAPS PharmSciTech 2009;10:289-96.
Dua K, Pabreja K, Ramana MV. Aceclofenac topical dosage forms: in vitro and in vivo characterization. Acta Pharm 2010;60:467-78.
El-Housiny S, Shams Eldeen MA, El-Attar YA, Salem HA, Attia D, Bendas ER, et al. Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study. Drug Delivery 2018;25:78-90.
Rajan R, Vasudevan DT. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole. J Adv Pharm Technol Res 2012;3:112-6.
Hosadurga RR, Rao SN, Jose J, Rompicharla NC, Shakil M, Shashidhara R. Evaluation of the efficacy of 2% curcumin gel in the treatment of experimental periodontitis. Pharmacogn Res 2014;6:326-33.
Shakeel F, Ramadan W, Ahmed MA. Investigation of true nanoemulsions for transdermal potential of indomethacin: characterization, rheological characteristics, and ex vivo skin permeation studies. J Drug Target 2009;17:435-41.
Patel D, Dasgupta S, Dey S, Ramani YR, Ray S, Mazumder B. Nanostructured lipid carriers (NLC) based gel for the topical delivery of aceclofenac: preparation, characterization, and in vivo evaluation. Sci Pharm 2012;80:749-64.
Ruela ALM, Figueiredo EC, Perissinato AG, Lima ACZ, Araujo MB, Pereira GR. In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil. Braz J Pharm Sci 2013;49:579-88.
Filon FL, Crosera M, Adami G, Bovenzi M, Rossi F, Maina G. Human skin penetration of gold nanoparticles through intact and damaged skin. Nanotoxicology 2011;5:493-501.
Sun L, Liu Z, Wang L, Cun D, Tong HHY, Yan R, et al. Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. J Controlled Release 2017;254:44-54.
Nimisha, Rizvi DA, Fatima Z, Neema, Kaur CD. Antipsoriatic and anti-inflammatory studies of Berberis aristata extract loaded nanovesicular gels. Pharmacogn Mag 2017;13(Suppl 3):S587-94.
Mangalathillam S, Rejinold NS, Nair A, Lakshmanan VK, Nair SV, Jayakumar R. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route. Nanoscale 2012;4:239-50.
Maboos M, Yousuf RI, Shoaib MH, Nasiri I, Hussain T, Ahmed HF, et al. Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets. Lipids Health Dis 2018;17:1-17.
Killen BU, Corrigan OI. Effect of soluble filler on drug release from stearic acid based compacts. Int J Pharm 2006;316:47-51.
Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: a co-surfactant study. Asian J Pharm Sci 2016;11:404-16.
Yuan Y, Chiba P, Cai T, Callaghan R, Bai L, Cole SPC, et al. Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells. Oncol Rep 2018;40:1055-63.
Dave V, Yadav RB, Kushwaha K, Yadav S, Sharma S, Agrawal U. Lipid-polymer hybrid nanoparticles: development and statistical optimization of norfloxacin for topical drug delivery system. Bioact Mater 2017;2:269-80.
Sharma D, Maheshwari D, Philip G, Rana R, Bhatia S, Singh M, et al. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using box-behnken design: in vitro and in vivo evaluation. BioMed Res Int 2014;156010:1-14.
Lerata MS, D'Souza S, Sibuyi NRS, Dube A, Meyer M, Samaai T, et al. Encapsulation of variabilin in stearic acid solid lipid nanoparticles enhances its anticancer activity in vitro. Molecules 2020;25:830-41.
Mundargi RC, Shelke NB, Rokhade AP, Patil SA, Aminabhavi TM. Formulation and in vitro evaluation of novel starch-based tableted microsphere for controlled release of ampicillin. Carbohydr Polym 2008;71:42-53.
Rajan SS, Pandian A, Palaniappan T. Curcumin loaded in bovine serum albumin-chitosan derived nanoparticles for targeted drug delivery. Bull Mater Sci 2016;39:811-7.
Akbari Z, Amanlou M, Karimi Sabet J, Golestani A, Niasar MS. Characterization of carbamazepine-loaded solid lipid nanoparticles prepared by rapid expansion of supercritical solution. Trop J Pharm Res 2014;13:1955-61.
Wu X, Zhang L, Zhang X, Zhu Y, Wu Y, Li Y, et al. Ethyl cellulose nanodispersions as stabilizers for oil in water pickering emulsions. Sci Rep 2017;7:1-10.
Tahir N, Madni A, Correia A, Rehman M, Balasubramanian V, Khan MM, et al. Lipid-polymer hybrid nanoparticles for controlled delivery of hydrophilic and lipophilic doxorubicin for breast cancer therapy. Int J Nanomed 2019;14:4961-74.
Mathew MS, Vinod K, Jayaram PS, Jayasree RS, Joseph K. Improved bioavailability of curcumin in the gliadin-protected gold quantum cluster for targeted delivery. ACS Omega 2009;4:14169-78.
Davidovich Pinhas M, Barbut S Marangoni AG. Physical structure and thermal behavior of ethylcellulose. Cellulose 2014;21:3243-55.
Farboud ES, Nasrollahi SA, Tabbakhi Z. Novel formulation and evaluation of a Q10-loaded solid lipid nanoparticle cream: in vitro and in vivo studies. Int J Nanomed 2011;6:611-7.
Ishak RAH, Mostafa NM, Kamel AO. Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain delivery-comparative study with the gold standard (Tween 80): optimization, characterization and biodistribution. Drug Delivery 2017;24:1874-90.
Wang W, Zhu R, Xie Q, Li A, Xiao Y, Li K, et al. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles. Int J Nanomed 2012;7:3667-77.
Mahnaj T, Ahmed SU, Plakogiannis FM. Characterization of ethyl cellulose polymer. Pharm Dev Technol 2013;18:982-9.
Wu B, Fu W, Kong B, Hu K, Zhou C, Lei J. Preparation and characterization of stearic acid/polyurethane composites as dual phase change material for thermal energy storage. J Therm Anal Calorim 2018;132:907-17.
Wang W, Chen T, Xu H, Ren B, Cheng X, Qi R, et al. Curcumin-loaded solid lipid nanoparticles enhanced anticancer efficiency in breast cancer. Molecules 2018;23:1578-90.
Mohan DC, Suresh A, Mukundan S, Gupta S, Viswanad V. Development and in vitro evaluation of nanolipid carriers of clobetasol propionate and pramoxine hydrochloride for topical delivery. Int J Appl Pharm 2018;10:28-36.
Tng DJ, Song P, Lin G, Soehartono AM, Yang G, Yang C, et al. Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer. Int J Nanomed 2015;10:5771-86.
Jain A, Agarwal A, Majumder S, Lariya N, Khaya A, Agrawal H, et al. Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug. J Controlled Release 2010;148:359-67.
Wang W, Zhu R, Xie Q, Li A, Xiao Y, Li K, et al. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles. Int J Nanomed 2012;7:3667-77.
Das S, Das MK. Synthesis and characterization of thiolated jackfruit seed starch as a colonic drug delivery carrier. Int J Appl Pharm 2019;11:53-62.
Magesh B, Naidu PY, Rajarajeswar GR. S-adenosyl-l-methionine (SAMe)-loaded nanochitosan particles: synthesis, characterisation and in vitro drug release studies. J Exp Nanosci 2015;10:828-43.
Lakhani P, Patil A, Taskar P, Ashour E, Majumdar S. Curcumin-loaded nanostructured lipid carriers for ocular drug delivery: design optimization and characterization. J Drug Delivery Sci Technol 2018;47:159-66.
Thakkar HP, Patel BV, Thakkar SP. Development and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement. J Pharm Bioallied Sci 2011;3:426-34.
Vandana D, Pawar S. Formulation and evaluation of topical herbal gel containing inclusion complex of curcumin. Asian J Pharm Clin Res 2019;12:196-201.
Zamarioli CM, Martins RM, Carvalho EC, Freitas LAP. Nanoparticles containing curcuminoids (Curcuma longa): development of topical delivery formulation. Rev Bras Farmacogn 2015;25:53-60.
Zakaria AS, Afifi SA, Elkhodairy KA. Newly developed topical cefotaxime sodium hydrogels: antibacterial activity and in vivo evaluation. Biomed Res Int 2016;6525163:1-15.
Fong Yen W, Basri M, Ahmad M, Ismail M. Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system. Sci World J 2015;495271:1-7.
Rajinikanth PS, Chellian J. Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil. Int J Nanomed 2016;11:5067-77.
Rapalli VK, Kaul V, Waghule T, Gorantla S, Sharma S, Roy A, et al. Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in vitro characterization and assessment of ex-vivo skin deposition. Eur J Pharm Sci 2020;152:1-55.
Kesharwani P, Jain A, Srivastava AK, Keshari MK. Systematic development and characterization of curcumin-loaded nanogel for topical application. Drug Dev Ind Pharm 2020;46:1443-57.
Tak YK, Pal S, Naoghare PK, Rangasamy S, Song JM. Shape-dependent skin penetration of silver nanoparticles: does it really matter? Sci Rep 2015;5:1-11.
Yuan J, Ni G, Wang T, Mounsey K, Cavezza S, Pan X, et al. Genital warts treatment: beyond imiquimod. Hum Vaccin Immunother 2018;14:1815-9.
Seifarth FG, Lax JE, Harvey J, DiCorleto PE, Husni ME, Chandrasekharan UM, et al. Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice. Cell Stress Chaperones 2018;23:1129-35.
Panonnummal R, Jayakumar R, Sabitha M. Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel and marketed cream. Eur J Pharm Sci 2017;96:193-206.
Sathe P, Saka R, Kommineni N, Raza K, Khan W. Dithranol-loaded nanostructured lipid carrier-based gel ameliorate psoriasis in imiquimod-induced mice psoriatic plaque model. Drug Dev Ind Pharm 2020;45:826-38.
Walunj M, Doppalapudi S, Bulbake U, Khan W. Preparation, characterization and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis. J Liposome Res 2020;30:68-79.
Moorchung N, Khullar J, Mani N, Chatterjee M, Vasudevan B, Tripathi T. A study of various histopathological features and their relevance in pathogenesis of psoriasis. Indian J Dermatol 2013;58:294-8.
Jia HY, Shi Y, Luo LF, Jiang G, Zhou Q, Xu SZ, et al. Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions. Int J Mol Med 2016;37:359-68.
Avasatthi V, Pawar H, Dora CP, Bansod P, Gill MS, Suresh S. A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization, in vitro and in vivo evaluation. Pharm Dev Technol 2016;21:554-62.
Khan MA, Pandit J, Sultana Y, Sultana S, Ali A, Aqil M, et al. Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study. Drug Delivery 2015;22:795-802.
Published
How to Cite
Issue
Section
