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Research Article

Skin-controlled release lipid nanosystems of pranoprofen for the treatment of local inflammation and pain

    María Rincón

    Department of Pharmacy & Pharmaceutical Technology & Physical Chemistry, Faculty of Pharmacy & Food Sciences, University of Barcelona, Barcelona, Spain

    ,
    Ana C Calpena

    Department of Pharmacy & Pharmaceutical Technology & Physical Chemistry, Faculty of Pharmacy & Food Sciences, University of Barcelona, Barcelona, Spain

    Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

    ,
    Beatriz Clares

    *Author for correspondence: Tel.: +34 9582 46664; Fax: +34 9582 48958;

    E-mail Address: beatrizclares@ugr.es

    Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

    Department of Pharmacy & Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain

    ,
    Marta Espina

    Department of Pharmacy & Pharmaceutical Technology & Physical Chemistry, Faculty of Pharmacy & Food Sciences, University of Barcelona, Barcelona, Spain

    Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

    ,
    María L Garduño-Ramírez

    Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México

    ,
    María J Rodríguez-Lagunas

    Department of Biochemistry & Physiology, Faculty of Pharmacy & Food Sciences, University of Barcelona, Barcelona, Spain

    ,
    María L García

    Department of Pharmacy & Pharmaceutical Technology & Physical Chemistry, Faculty of Pharmacy & Food Sciences, University of Barcelona, Barcelona, Spain

    Institute of Nanoscience & Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

    Authors contributed equally

    Search for more papers by this author

    &
    Guadalupe Abrego

    Department of Chemical & Instrumental Analysis, Faculty of Chemistry & Pharmacy, University of El Salvador, San Salvador, El Salvador

    Authors contributed equally

    Search for more papers by this author

    Published Online:https://doi.org/10.2217/nnm-2018-0195

    Aim: The design and development of pranoprofen (PF) nanostructured lipid carriers (NLCs) for topical treatment of local inflammation and pain. Materials & methods: PF-NLCs were designed and optimized by central rotatable composite design. A physicochemical characterization was addressed. Release and skin permeation were performed in Franz diffusion cells. In vivo anti-inflammatory efficacy was assayed in mice and tolerance study in humans. Results: PF-NLCs F7 and F10 provided sustained release, good stability and optimal skin retention avoiding systemic undesired side effects. Anti-inflammatory activity was enhanced, suggesting an improved efficacy as compared with standard formulation. No skin irritancy was detected. Conclusion: Topical PF-NLCs F7 and F10 could be effective and safe new therapeutic tools for the treatment of local inflammation and pain.

    Papers of special note have been highlighted as: • of interest •• of considerable interest

    References

    • 1 Komatsu T, Sakurada T. Comparison of the efficacy and skin permeability of topical NSAID preparations used in Europe. Eur. J. Pharm. Sci. 47(5), 890–895 (2012).
    • 2 Hochberg MC, Altman RD, April KT et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip and knee. Arthritis Care Res. 64(4), 465–474 (2012).
    • 3 Zhang W, Moskowitz RW, Nuki G et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr. Cartil. 16(2), 137–162 (2008). • Representative review of recommendations for the management of hip and knee osteoarthritis to assist physicians.
    • 4 NICE. Osteoarthritis care and management in adults: methods, evidence and recommendations. Report No. CG177. National Institute for Health and Care Excellence, London (2014). https://www.ncbi.nlm.nih.gov/books/NBK248069/pdf/Bookshelf_NBK248069.pdf • Representative guideline for assessing and managing osteoarthritis including pharmacological and nonpharmacological treatments.
    • 5 Bruyere O, Cooper C, Pelletier JP et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin. Arthritis Rheum. 44(3), 253–263 (2014).
    • 6 Abrego G, Alvarado H, Souto EB et al. Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration. Eur. J. Pharm. Biopharm. 95(Pt B) 261–270 (2015).
    • 7 Choi JS, Shin SC. Enhanced bioavailability by transdermal administration of pranoprofen gels containing octanoic acid to rats. Biomol. Ther. (Seoul) 163(3), 210–214 (2008).
    • 8 Abrego G, Alvarado H, Souto EB et al. Biopharmaceutical profile of hydrogels containing pranoprofen-loaded PLGA nanoparticles for skin administration: In vitro, ex vivo and in vivo characterization. Int. J. Pharm. 501(1–2) 350–261 (2016).
    • 9 Bruyère O, Altman RD, Reginster JY. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin. Arthritis Rheum. 45(Suppl. 4) S12–S17 (2016).
    • 10 Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J. Rheumatol. 37(6), 1236–1243 (2010).
    • 11 Arnstein PM. Evolution of topical NSAIDs in the guidelines for treatment of osteoarthritis in elderly patients. Drugs Aging 29(7), 523–531 (2012). •• Excellent contribution dealing with treatments that are available to the treatment of osteoarthritis in such high-risk patient population.
    • 12 Method for stabilizing pranoprofen and stable liquid preparation of pranoprofen: US5856345A. (1999).
    • 13 Sustained-release pranoprofen preparation. US5225206A (1993).
    • 14 Fraenkel L, Wittink DR, Concato J, Fried T. Informed choice and the widespread use of anti-inflammatory drugs. Arthritis Rheum. 51(2). 210–214 (2004).
    • 15 Alvarado HL, Abrego G, Souto EB et al. Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization. Colloids Surf. B Biointerfaces 130, 40–47 (2015).
    • 16 McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 14(Suppl. 1), S35–S39 (2013).
    • 17 Parra A, Clares B, Rossello A et al. Ex vivo permeation of carprofen from nanoparticles: a comprehensive study through human, porcine and bovine skin as anti-inflammatory agent. Int. J. Pharm. 50(1–2), 10–17 (2016).
    • 18 Manca ML, Zaru M, Manconi M et al. Glycerosomes: a new tool for effective dermal and transdermal drug delivery. Int. J. Pharm. 455(1–2), 66–74 (2013).
    • 19 Mallandrich M, Fernández-Campos F, Clares B et al. Developing transdermal applications of ketorolac tromethamine entrapped in stimuli sensitive block copolymer hydrogels. Pharm. Res. 34(8), 1728–1740 (2017).
    • 20 Moner V, Fernández E, Calpena AC, Garcia-Herrera A, Cócera M, López O. A lamellar body mimetic system for the treatment of oxazolone-induced atopic dermatitis in hairless mice. J. Dermatol. Sci. 90(2), 172–179 (2018).
    • 21 Lam PL, Gambari R. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and trans-dermal drug deliveries. J. Control. Rel. 178, 25–45 (2014).
    • 22 Silva-Abreu M, Espinoza LC, Rodríguez-Lagunas MJ et al. Human skin permeation studies with PPARγ agonist to improve its permeability and efficacy in inflammatory processes. Int. J. Mol. Sci. 18(12), 2548 (2017).
    • 23 Montenegro L, Lai F, Offerta A et al. From nanoemulsions to nanostructured lipid carriers: a relevant development in dermal delivery of drugs and cosmetics. J. Drug Deliv. Sci. Technol. 62(Part B), 100–112 (2016). • Descriptive review about nano-carriers properties specifically designed for dermal delivery.
    • 24 Domínguez-Villegas V, Clares-Naveros B, García-López ML, Calpena-Campmany AC, Bustos-Zagal P, Garduño-Ramírez ML. Development and characterization of two nano-structured systems for topical application of flavanones isolated from Eysenhardtia platycarpa. Colloids Surf. B Biointerfaces 116, 183–192 (2014).
    • 25 Manca ML, Manconi M, Nacher A et al. Development of novel diolein-niosomes for cutaneous delivery of tretinoin: Influence of formulation and in vitro assessment. Int. J. Pharm. 477(1–2), 176–186 (2014).
    • 26 Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V. Nanostructured lipid carriers: promising drug-delivery systems for future clinics. Nanomedicine 12, 143–161 (2016).
    • 27 Müller RH, Petersen RD, Hommoss A, Pardeike J. Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv. Drug. Deliv. Rev. 59, 522–530 (2007).
    • 28 González-Mira E, Egea MA, Garcia ML, Souto EB. Design and ocular tolerance of flurbiprofen-loaded ultrasound-engineered NLC. Colloids Surf. B Biointerfaces 81, 412–421 (2010).
    • 29 Silva AC, González-Mira E, García ML et al. Preparation, characterization and biocompatibility studies on risperidona-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids Surf. B Biointerfaces 86, 158–165 (2011).
    • 30 Manca ML, Valenti D, Sales OD, Nacher A, Fadda AM, Manconi M. Fabrication of polyelectrolyte multilayered vesicles as inhalable dry powder for lung administration of rifampicin. Int. J. Pharm. 472(1–2), 102–109 (2014).
    • 31 Manca ML, Manconi M, Zaru M et al. Glycerosomes: investigation of role of 1,2-dimyristoyl-sn-glycero-3-phosphatidycholine (DMPC) on the assembling and skin delivery performances. Int. J. Pharm. 532(1), 401–407 (2017).
    • 32 Suñer J, Calpena AC, Clares B, Cañadas C, Halbaut L. Development of clotrimazole multiple W/O/W emulsions as vehicles for drug delivery: effects of additives on emulsion stability. AAPS PharmSciTech. 18(2), 539–550 (2017).
    • 33 International Conference on Harmonization (ICH). Validation of analytical procedures: text and methodology, Q2(R1). ICH, Geneva, Switzerland (2005).
    • 34 Sánchez-López E, Ettcheto M, Egea MA et al. New potential strategies for Alzheimer's disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9. Nanomedicine 13(3), 1171–1182 (2017).
    • 35 International Conference on Harmonization (ICH). Stability testing of new drug substances and products, Q1A(R2). ICH, Geneva, Switzerland (2003).
    • 36 World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310(20), 2191–2194 (2013).
    • 37 Sosa L, Clares B, Alvarado HL, Bozal N, Domenech O, Calpena AC. Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis. Nanomedicine 13(7), 2303–2312 (2017).
    • 38 Liu D, Ge Y, Tang Y et al. Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies. J. Microencapsul. 27(8), 726–734 (2010).
    • 39 Abrego G, Alvarado HL, Egea MA, González-Mira E, Calpena AC, García ML. Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen. J. Pharm. Sci. 103(10), 3153–3164 (2014).
    • 40 Kohli AK, Alpar HO. Potential use of nanoparticles for transcutaneous vaccine delivery: effect of particle size and charge. Int. J. Pharm. 275, 13–17 (2004).
    • 41 Parra A, Mallandrich M, Clares B et al. Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: ocular anti-inflammatory applications. Colloids Surf. B Biointerfaces 136, 935–943 (2015).
    • 42 Ciurlizza C, Fernández F, Calpena AC, Lázaro R, Parra A, Clares B. Semisolid formulations containing cetirizine: human skin permeation and topical antihistaminic evaluation in a rabbit model. Arch. Dermatol. Res. 306(8), 711–717 (2014).
    • 43 Dimitrova TD, Leal-Calderon F. Forces between emulsion droplets stabilized with Tween 20 and proteins. Langmuir 15, 8813–8821 (1999).
    • 44 Alvarado HL, Abrego G, Garduño-Ramirez ML, Clares B, Calpena AC, García ML. Design and optimization of oleanolic/ursolic acid loaded nanoplatforms for ocular anti-inflammatory applications. Nanomedicine 11(3), 521–230 (2015).
    • 45 Papadopoulou V, Kosmidis K, Vlachou M, Macheras P. On the use of the Weibull function for the discernment of drug release mechanisms. Int. J. Pharm. 309(1–2), 44–50 (2006).
    • 46 Mohammed D, Hirata K, Hadgraft J, Lane ME. Influence of skin penetration enhancers on skin barrier function and skin protease activity. Eur. J. Pharm. Sci. 51, 118–122 (2014).
    • 47 Estanqueiro M, Conceição J, Amaral MH, Sousa Lobo JM. Characterization, sensorial evaluation and moisturizing efficacy of nanolipidgel formulations. Int. J. Cosmet. Sci. 36(2), 159–166 (2014).
    • 48 Bookman AA, Williams KS, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. CMAJ 171(4), 333–338 (2004).
    • 49 Cooper SM, Shaw S. Contact allergy to isopropanolamine in Traxam gel. Contact Dermatitis 41(4), 233–234 (1999).
    • 50 Doktorovova S, Kovačević AB, Garcia ML, Souto EB. Preclinical safety of solid lipid nanoparticles and nanostuctured lipid carriers: Current evidence from in vitro and in vivo evaluation. Eur. J. Pharm. Biopharm. 108, 235–252 (2016).