Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery

References

• Gupta M, Agrawal U, Vyas SP. Nanocarrier-based topical drug delivery for the treatment of skin diseases. Expert Opin Drug Deliv. 2012;9(7):783–804.
   PubMed Web of Science ®Google Scholar
• Schäfer-Korting M, Mehnert W, Korting H-C. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev. 2007;59(6):427–443.
   PubMed Web of Science ®Google Scholar
• Bariya SH, Gohel MC, Mehta TA, et al. Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol. 2012;64(1):11–29.
   PubMed Web of Science ®Google Scholar
• Kristl J, Teskač K, Grabnar PA. Current view on nanosized solid lipid carriers for drug delivery to the skin. J Biomed Nanotechnol. 2010;6(5):529–542.
   PubMed Web of Science ®Google Scholar
• Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14(2):101–114.
   PubMed Web of Science ®Google Scholar
• Barry BW. Breaching the skin’s barrier to drugs. Nat Biotechnol. 2004;22(2):165–167.
   PubMed Web of Science ®Google Scholar
• Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16–20.
   PubMed Web of Science ®Google Scholar
• Korting HC, Schäfer-Korting M. Carriers in the topical treatment of skin disease. Drug Deliv. Springer; 2010;197: 435–468.
   Google Scholar
• Petrak K. Nanotechnology and site-targeted drug delivery. J Biomater Sci Polymer. Edition. 2006;17(11): 1209–1219.
   PubMed Web of Science ®Google Scholar
• Cevc G, Vierl U. Nanotechnology and the transdermal route: a state of the art review and critical appraisal. J Control Release. 2010;141(3):277–299.
   PubMed Web of Science ®Google Scholar
• Schroeter A, Engelbrecht T, Neubert RH, et al. New nanosized technologies for dermal and transdermal drug delivery a review. J Biomed Nanotechnol. 2010;6(5):511–528.
   PubMed Web of Science ®Google Scholar
• Nohynek G, Dufour E, Roberts M. Nanotechnology, cosmetics and the skin: is there a health risk? Skin Pharmacol Physiol. 2008;21(3):136–149.
   PubMed Web of Science ®Google Scholar
• Souto E, Almeida A, Müller R. Lipid nanoparticles (SLN, NLC) for cutaneous drug delivery: structure, protection and skin effects. J Biomed Nanotechnol. 2007;3(4):317–331.
   Web of Science ®Google Scholar
• Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366(1):170–184.
   PubMed Web of Science ®Google Scholar
• Junghanns J, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed. 2008;3(3):295–309.
   PubMed Web of Science ®Google Scholar
• Sharma OP, Patel V, Mehta T. Nanocrystal for ocular drug delivery: hope or hype. Drug Deliv Transl Res. 2016;6(4):399–413.
   PubMed Web of Science ®Google Scholar
• Lademann J, Richter H, Meinke MC, et al. Drug delivery with topically applied nanoparticles: science fiction or reality. Skin Pharmacol Physiol. 2013;26(4–6):227–233.
   PubMed Web of Science ®Google Scholar
• Prow TW, Grice JE, Lin LL, et al. Nanoparticles and microparticles for skin drug delivery. Adv Drug Deliv Rev. 2011;63(6):470–491.
   PubMed Web of Science ®Google Scholar
• Adib ZM, Ghanbarzadeh S, Kouhsoltani M, et al. The effect of particle size on the deposition of solid lipid nanoparticles in different skin layers: A histological study. Adv Pharm Bulletin. 2016;6(1):31.
   PubMed Web of Science ®Google Scholar
• Surber C, Smith EW. The mystical effects of dermatological vehicles. Dermatology. 2005;210(2):157–168.
   PubMed Web of Science ®Google Scholar
• Scheuplein RJ. Mechanism of percutaneous absorption: II. Transient diffusion and the relative importance of various routes of skin penetration. J Invest Dermatol. 1967;48(1):79–88.
   PubMed Web of Science ®Google Scholar
• Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev. 1971;51(4):702–747.
   PubMed Web of Science ®Google Scholar
• Elias PM, Friend DS. The permeability barrier in mammalian epidermis. J Cell Biol. 1975;65(1):180–191.
   PubMed Web of Science ®Google Scholar
• Gaur M, Dobke M, Lunyak VV. Mesenchymal stem cells from adipose tissue in clinical applications for dermatological indications and skin aging. Int J Molecular Sci. 2017;18(1):208.
   Web of Science ®Google Scholar
• Van Hal DA, Jeremiasse E, Junginger HE, et al. Structure of fully hydrated human stratum corneum: a freeze-fracture electron microscopy study. J Invest Dermatol. 1996;106(1):89–95.
   PubMed Web of Science ®Google Scholar
• Lerner AB. Physiology, biochemistry, and molecular biology of the skin. Arch Dermatol. 1993;129(2):255–255.
   Google Scholar
• Breathnach AS. Aspects of epidermal ultrastructure. J Invest Dermatol. 1975;65(1):2–15.
   PubMed Web of Science ®Google Scholar
• Simanski M, Gläser R, Harder J. Human skin engages different epidermal layers to provide distinct innate defense mechanisms. Exp Dermatol. 2014;23(4):230–231.
   PubMed Web of Science ®Google Scholar
• Wiechers JW. The barrier function of the skin in relation to percutaneous absorption of drugs. Pharm Weekbl. 1989;11(6):185–198.
   Google Scholar
• Nemes Z, Steinert PM. Bricks and mortar of the epidermal barrier. Exp Mol Med. 1999;31(1):5–19.
   PubMed Web of Science ®Google Scholar
• Trommer H, Neubert R. Overcoming the stratum corneum: the modulation of skin penetration. Skin Pharmacol Physiol. 2006;19(2):106–121.
   PubMed Web of Science ®Google Scholar
• Wiechers JW. The barrier function of the skin in relation to percutaneous absorption of drugs. Pharm World Sci. 1989;11(6):185–198.
   Google Scholar
• Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol. 2008;17(12):1063–1072.
   PubMed Web of Science ®Google Scholar
• Barry BW. Mode of action of penetration enhancers in human skin. J Control Release. 1987;6(1):85–97.
   Google Scholar
• Baroni A, Buommino E, De Gregorio V, et al. Structure and function of the epidermis related to barrier properties. Clin Dermatol. 2012;30(3):257–262.
   PubMed Web of Science ®Google Scholar
• Cichorek M, Wachulska M, Stasiewicz A, et al. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013;30(1):30–41.
   PubMed Web of Science ®Google Scholar
• Chomiczewska D, Trznadel-Budźko E, Kaczorowska A, et al. The role of Langerhans cells in the skin immune system. Polski Merkuriusz Lekarski. 2009;26(153):173–177.
   PubMedGoogle Scholar
• Hogan A, Burks AW. Epidermal Langerhans’ cells and their function in the skin immune system. Ann Allergy Asthma Im. 1995;75(1):5–10; 10–2.
   PubMed Web of Science ®Google Scholar
• Munde PB, Khandekar SP, Dive AA, et al. Pathophysiology of merkel cell. J Oral Maxillofac Pathol. 2013;17(3):408.
   PubMedGoogle Scholar
• Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol. 2008;8(12):935–947.
   PubMed Web of Science ®Google Scholar
• Briggaman RA, Wheeler CE. The epidermal-dermal junction. J Invest Dermatol. 1975;65(1):71–84.
   PubMed Web of Science ®Google Scholar
• Squier C, Lesch C. Penetration pathways different compounds through epidermis and oral epithelia. J Oral Pathol Med. 1988;17(9‐10):512–516.
   Web of Science ®Google Scholar
• Bolzinger M-A, Briançon S, Pelletier J, et al. Penetration of drugs through skin, a complex rate-controlling membrane. Curr Opin Colloid Interface Sci. 2012;17(3):156–165.
   Web of Science ®Google Scholar
• Alvarez-Román R, Naik A, Kalia Y, et al. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99(1):53–62.
   PubMed Web of Science ®Google Scholar
• Lademann J, Otberg N, Richter H, et al. Investigation of follicular penetration of topically applied substances. Skin Pharmacol Physiol. 2001;14(Suppl. 1):17–22.
   Google Scholar
• Sznitowska M, Janicki S, Williams AC. Intracellular or intercellular localization of the polar pathway of penetration across stratum corneum. J Pharm Sci. 1998;87(9):1109–1114.
   PubMed Web of Science ®Google Scholar
• Dayan N. Pathways for skin penetration. Cosmetics & Toiletries. 2005;120(6):67–76.
   Google Scholar
• Barry B. Drug delivery routes in skin: a novel approach. Adv Drug Deliv Rev. 2002;54:S31–S40.
   PubMed Web of Science ®Google Scholar
• Beaurline JM, Roddy PJ, Tomai MA, inventor; Medicis Pharmaceutical Corp, assignee. Gel formulations for topical drug delivery. US5939090A. 1999.
   Google Scholar
• Batheja P, Sheihet L, Kohn J, et al. Topical drug delivery by a polymeric nanosphere gel: formulation optimization and in vitro and in vivo skin distribution studies. J Control Release. 2011;149(2):159–167.
   PubMed Web of Science ®Google Scholar
• Madison KC. Barrier function of the skin:“la raison d’etre” of the epidermis. J Invest Dermatol. 2003;121(2):231–241.
   PubMed Web of Science ®Google Scholar
• Singh Malik D, Mital N, Kaur G. Topical drug delivery systems: a patent review. Expert Opin Ther Pat. 2016;26(2):213–228.
   PubMed Web of Science ®Google Scholar
• Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technol Today. 2000;3(9):318–326.
   PubMedGoogle Scholar
• Proksch E, Fölster-Holst R, Jensen J-M. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci. 2006;43(3):159–169.
   PubMed Web of Science ®Google Scholar
• Paudel KS, Milewski M, Swadley CL, et al. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv. 2010;1(1):109–131.
   PubMedGoogle Scholar
• Moser K, Kriwet K, Naik A, et al. Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm. 2001;52(2):103–112.
   PubMed Web of Science ®Google Scholar
• Betz G, Nowbakht P, Imboden R, et al. Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro. Int J Pharm. 2001;228(1):147–159.
   PubMedGoogle Scholar
• Kadir R, Stempler D, Liron Z, et al. Delivery of theophylline into excised human skin from alkanoic acid solutions: A “push‐pull” mechanism. J Pharm Sci. 1987;76(10):774–779.
   PubMed Web of Science ®Google Scholar
• Kadir R, Stempler D, Liron Z, et al. Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant. J Pharm Sci. 1989;78(2):149–153.
   PubMed Web of Science ®Google Scholar
• Guy RH, Hadgraft J. Physicochemical aspects of percutaneous penetration and its enhancement. Pharm Res. 1988;5(12):753–758.
   PubMed Web of Science ®Google Scholar
• Brown MB, Martin GP, Jones SA, et al. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006;13(3):175–187.
   PubMed Web of Science ®Google Scholar
• Zhang H, Zhai Y, Yang X, et al. Breaking the skin barrier: achievements and future directions. Curr Pharm Des. 2015;21(20):2713–2724.
   PubMed Web of Science ®Google Scholar
• Ferreira M, Silva E, Barreiros L, et al. Methotrexate loaded lipid nanoparticles for topical management of skin-related diseases: design, characterization and skin permeation potential. Int J Pharm. 2016;512(1):14–21.
   PubMedGoogle Scholar
• Kaur A, Goindi S, Katare OP. Formulation, characterisation and in vivo evaluation of lipid-based nanocarrier for topical delivery of diflunisal. J Microencapsul. 2016;33(5):475–486.
   PubMed Web of Science ®Google Scholar
• Alves MP, Scarrone AL, Santos M, et al. Human skin penetration and distribution of nimesulide from hydrophilic gels containing nanocarriers. Int J Pharm. 2007;341(1):215–220.
   PubMedGoogle Scholar
• Davis S. Biomedical applications of nanotechnology—implications for drug targeting and gene therapy. Trends Biotechnol. 1997;15(6):217–224.
   PubMed Web of Science ®Google Scholar
• Chen Y, Wu Q, Zhang Z, et al. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules. 2012;17(5):5972–5987.
   PubMed Web of Science ®Google Scholar
• Li S, Qiu Y, Zhang S, et al. A novel transdermal fomulation of 18β-glycyrrhetic acid with lysine for improving bioavailability and efficacy. Skin Pharmacol Physiol. 2012;25(5):257–268.
   PubMed Web of Science ®Google Scholar
• Li N, Peng L-H, Chen X, et al. Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo. Int J Nanomed. 2011;6:3241–3250.
   PubMed Web of Science ®Google Scholar
• Kirjavainen M, Urtti A, Valjakka-Koskela R, et al. Liposome–skin interactions and their effects on the skin permeation of drugs. Eur J Pharm Sci. 1999;7(4):279–286.
   PubMed Web of Science ®Google Scholar
• Verma D, Verma S, Blume G, et al. Liposomes increase skin penetration of entrapped and non-entrapped hydrophilic substances into human skin: a skin penetration and confocal laser scanning microscopy study. Eur J Pharm Biopharm. 2003;55(3):271–277.
   PubMed Web of Science ®Google Scholar
• Kirjavainen M, Urtti A, Jääskeläinen I, et al. Interaction of liposomes with human skin in vitro—the influence of lipid composition and structure. Acta Lipids Lipid Met. 1996;1304(3):179–189.
   PubMed Web of Science ®Google Scholar
• Jung S, Otberg N, Thiede G, et al. Innovative liposomes as a transfollicular drug delivery system: penetration into porcine hair follicles. J Invest Dermatol. 2006;126(8):1728–1732.
   PubMed Web of Science ®Google Scholar
• Sharma G, Saini MK, Thakur K, et al. Aceclofenac cocrystal nanoliposomes for rheumatoid arthritis with better dermatokinetic attributes: a preclinical study. Nanomedicine. 2017;12(6):615–638.
   PubMed Web of Science ®Google Scholar
• Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug. 1996;13:3–4.
   Web of Science ®Google Scholar
• Baspinar Y, Borchert -H-H. Penetration and release studies of positively and negatively charged nanoemulsions—is there a benefit of the positive charge? Int J Pharm. 2012;430(1):247–252.
   PubMed Web of Science ®Google Scholar
• Sonneville-Aubrun O, Simonnet J-T, L’alloret F. Nanoemulsions: a new vehicle for skincare products. Adv Colloid Interface Sci. 2004;108:145–149.
   PubMed Web of Science ®Google Scholar
• Mou D, Chen H, Du D, et al. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm. 2008;353(1):270–276.
   PubMedGoogle Scholar
• Müller R, Maaβen S, Weyhers H, et al. Cytotoxicity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles. Int J Pharm. 1996;138(1):85–94.
   Web of Science ®Google Scholar
• Jenning V, Gysler A, Schäfer-Korting M, et al. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm. 2000;49(3):211–218.
   PubMed Web of Science ®Google Scholar
• Üner M. Characterization and imaging of solid lipid nanoparticles and nanostructured lipid carriers. Handbook of Nanoparticles. Springer; 2016. p. 117–141.
   Google Scholar
• Wester RC, Patel R, Nacht S, et al. Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. J Am Acad Dermatol. 1991;24(5):720–726.
   PubMed Web of Science ®Google Scholar
• Masini V, Bonte F, Meybeck A, et al. Cutaneous bioavailability in hairless rats of tretinoin in liposomes or gel. J Pharm Sci. 1993;82(1):17–21.
   PubMed Web of Science ®Google Scholar
• Schäfer-Korting M, Korting H, Ponce-Pöschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Invest. 1994;72(12):1086–1091.
   PubMedGoogle Scholar
• Puglia C, Offerta A, Tirendi GG, et al. Design of solid lipid nanoparticles for caffeine topical administration. Drug Deliv. 2016;23(1):36–40.
   PubMed Web of Science ®Google Scholar
• Butani D, Yewale C, Misra A. Topical Amphotericin B solid lipid nanoparticles: design and development. Colloids Surf B Biointer. 2016;139:17–24.
   PubMed Web of Science ®Google Scholar
• Embil K, Nacht S. The microsponge delivery system (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives. J Microencapsul. 1996;13(5):575–588.
   PubMed Web of Science ®Google Scholar
• De Vringer T, De Ronde H. Preparation and structure of a water‐in‐oil cream containing lipid nanoparticles. J Pharm Sci. 1995;84(4):466–472.
   PubMed Web of Science ®Google Scholar
• Akbari J, Saeedi M, Morteza-Semnani K, et al. The design of naproxen solid lipid nanoparticles to target skin layers. Colloids Surf B Biointer. 2016;145:626–633.
   PubMed Web of Science ®Google Scholar
• Sharma G, Thakur K, Raza K, et al. Nanostructured lipid carriers: a new paradigm in topical delivery for dermal and transdermal applications. Crit Rev Ther Drug. 2017;34(4):355-386.
   Web of Science ®Google Scholar
• Müller RH, Alexiev U, Sinambela P, et al. Nanostructured Lipid Carriers (NLC): the second generation of solid lipid nanoparticles. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg; 2016. p.161–185.
   Google Scholar
• Beloqui A, Solinís MÁ, Rodríguez-Gascón A, et al. Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomed Nanotechnol Biol Med. 2016;12(1):143–161.
   PubMed Web of Science ®Google Scholar
• Ghate VM, Lewis SA, Prabhu P, et al. Nanostructured lipid carriers for the topical delivery of tretinoin. Eur J Pharm Biopharm. 2016;108:253–261.
   PubMed Web of Science ®Google Scholar
• Doktorovová S, Kovačević AB, Garcia ML, et al. Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: current evidence from in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2016;108:235–252.
   PubMed Web of Science ®Google Scholar
• Solans C, Izquierdo P, Nolla J, et al. Nano-emulsions. Curr Opin Colloid Interface Sci. 2005;10(3):102–110.
   Web of Science ®Google Scholar
• Zhang Z, Tsai PC, Ramezanli T, et al. Polymeric nanoparticles‐based topical delivery systems for the treatment of dermatological diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013;5(3):205–218.
   PubMed Web of Science ®Google Scholar
• Egbaria K, Weiner N. Liposomes as a topical drug delivery system. Adv Drug Deliv Rev. 1990;5(3):287–300.
   Google Scholar
• Touitou E, Godin B, Weiss C. Enhanced delivery of drugs into and across the skin by ethosomal carriers. Drug Dev Res. 2000;50(3‐4):406–415.
   Web of Science ®Google Scholar
• Elsayed MM, Abdallah OY, Naggar VF, et al. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int J Pharm. 2006;322(1):60–66.
   PubMedGoogle Scholar
• Benson HA. Transfersomes for transdermal drug delivery. Expert Opin Drug Deliv. 2006;3(6):727–737.
   PubMedGoogle Scholar
• 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:S131–S155.
   PubMed Web of Science ®Google Scholar
• Müller R, Petersen R, Hommoss A, et al. Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev. 2007;59(6):522–530.
   PubMed Web of Science ®Google Scholar
• Choi M, Maibach H. Liposomes and niosomes as topical drug delivery systems. Skin Pharmacol Physiol. 2005;18(5):209–219.
   PubMed Web of Science ®Google Scholar
• Giandalia G, De Caro V, Cordone L, et al. Trehalose–hydroxyethylcellulose microspheres containing vancomycin for topical drug delivery. Eur J Pharm Biopharm. 2001;52(1):83–89.
   PubMed Web of Science ®Google Scholar
• Naik A, Kalia YN, Guy RH, et al. Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res. 2004;21(10):1818–1825.
   PubMed Web of Science ®Google Scholar
• Ramezanli T, Zhang Z, Michniak-Kohn BB. Development and characterization of polymeric nanoparticle-based formulation of adapalene for topical acne therapy. Nanomed Nanotechnol Biol Med. 2017;13(1):143–152.
   PubMed Web of Science ®Google Scholar
• Mandawgade SD, Patravale VB. Development of SLNs from natural lipids: application to topical delivery of tretinoin. Int J Pharm. 2008;363(1):132–138.
   PubMedGoogle Scholar
• Bhol K, Schechter P. Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis. Br J Dermatol. 2005;152(6):1235–1242.
   PubMed Web of Science ®Google Scholar
• Patravale V, Kulkarni R. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827–840.
   PubMed Web of Science ®Google Scholar
• Petersen R, inventor; AbbVie Deutschland GmbH and Co KG, assignee. Nanocrystals for use in topical cosmetic formulations and method of production thereof. US9114077B2. 2015.
   Google Scholar
• Kobierski S, Ofori-Kwakye K, Müller R, et al. Resveratrol nanosuspensions: interaction of preservatives with nanocrystal production. Die Pharmazie Int J Pharm Sci. 2011;66(12):942–947.
   Google Scholar
• Al Shaal L, Shegokar R, Müller RH. Production and characterization of antioxidant apigenin nanocrystals as a novel UV skin protective formulation. Int J Pharm. 2011;420(1):133–140.
   PubMedGoogle Scholar
• Mitri K, Shegokar R, Gohla S, et al. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int J Pharm. 2011;420(1):141–146.
   PubMed Web of Science ®Google Scholar
• Shegokar R, Mitri K. Carotenoid lutein: a promising candidate for pharmaceutical and nutraceutical applications. J Diet Suppl. 2012;9(3):183–210.
   PubMedGoogle Scholar
• Chen H, Khemtong C, Yang X, et al. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today. 2011;16(7):354–360.
   PubMed Web of Science ®Google Scholar
• Gao L, Liu G, Ma J, et al. Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs. Pharm Res. 2013;30(2):307–324.
   PubMed Web of Science ®Google Scholar
• Sharma OP, Patel V, Mehta T. Design of experiment approach in development of febuxostat nanocrystal: application of Soluplus as stabilizer. Powder Technol. 2016;302:396–405.
   Web of Science ®Google Scholar
• Müller RH, Gohla S, Keck CM. State of the art of nanocrystals–special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9.
   PubMed Web of Science ®Google Scholar
• Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2006;62(1):3–16.
   PubMed Web of Science ®Google Scholar
• Liversidge E, Marty J Nanocrystals: resolving pharmaceutical formulation issues associated with poorly water soluble compounds. Orlando: Particles Marcel Dekker; 2002.
   Google Scholar
• Agarwal V, Bajpai M. Nanosuspension technology for poorly soluble drugs: recent researches, advances and patents. Recent Pat Nanotechnol. 2015;9(3):178–194.
   PubMed Web of Science ®Google Scholar
• Müller R, Hildebrand G. Pharmazeutische technologie: moderne Arzneiformen. Auflage, Wiss Verlagsges mbH, Stuttgart, Baden-Württemberg, Germany; 1998.
   Google Scholar
• Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1):129–139.
   PubMedGoogle Scholar
• Van Eerdenbrugh B, Van den Mooter G, Augustijns P. Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. Int J Pharm. 2008;364(1):64–75.
   PubMed Web of Science ®Google Scholar
• Müller R, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Adv Drug Deliv Rev. 2001;47(1):3–19.
   PubMed Web of Science ®Google Scholar
• Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanoparticle Res. 2008;10(5):845–862.
   Web of Science ®Google Scholar
• Kipp JE, Wong JCT, Doty MJ, et al, inventor; Baxter International Inc., assignee. Method for preparing submicron particle suspensions. US6884436 B2. 2005.
   Google Scholar
• Kipp JE, Wong JCT, Doty MJ, et al, inventor; Baxter International Inc., assignee. Microprecipitation method for preparing submicron suspensions. US7037528 B2. 2003.
   Google Scholar
• Möschwitzer J, Müller RH. New method for the effective production of ultrafine drug nanocrystals. J Nanosci Nanotechnol. 2006;6(9–1):3145–3153.
   PubMed Web of Science ®Google Scholar
• Sinha B, Müller RH, Möschwitzer JP. Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm. 2013;453(1):126–141.
   PubMedGoogle Scholar
• Gao Y, Wang J, Wang Y, et al. Crystallization methods for preparation of nanocrystals for drug delivery system. Curr Pharm Des. 2015;21(22):3131–3139.
   PubMed Web of Science ®Google Scholar
• Xia D, Gan Y, Cui F. Application of precipitation methods for the production of water-insoluble drug nanocrystals: production techniques and stability of nanocrystals. Curr Pharm Des. 2014;20(3):408–435.
   PubMed Web of Science ®Google Scholar
• Chan H-K, Kwok PCL. Production methods for nanodrug particles using the bottom-up approach. Adv Drug Deliv Rev. 2011;63(6):406–416.
   PubMed Web of Science ®Google Scholar
• Verma S, Gokhale R, Burgess DJ. A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm. 2009;380(1):216–222.
   PubMedGoogle Scholar
• Peltonen L, Hirvonen J. Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods. J Pharm Pharmacol. 2010;62(11):1569–1579.
   PubMed Web of Science ®Google Scholar
• Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015;10(1):13–23.
   Web of Science ®Google Scholar
• Salazar J, Müller RH, Möschwitzer JP. Combinative particle size reduction technologies for the production of drug nanocrystals. J Pharm. 2014;2014:1-14.
   Google Scholar
• Keck C, Kobierski S, Mauludin R, et al. Second generation of drug nanocrystals for delivery of poorly soluble drugs: smartCrystals technology. Dosis. 2008;24(2):124–128.
   Google Scholar
• Junghanns J-UA, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed. 2008;3(3):295.
   PubMed Web of Science ®Google Scholar
• Müller RH, Shegokar R, Gohla S, et al. Nanocrystals: production, cellular drug delivery, current and future products. Intracellular Delivery. Fundamental Biomedical Technologies, vol 5. Springer, Dordrecht; 2011. p. 411–432.
   Google Scholar
• Lai F, Schlich M, Pireddu R, et al. Production of nanosuspensions as a tool to improve drug bioavailability: focus on topical delivery. Curr Pharm Des. 2015;21(42):6089–6103.
   PubMed Web of Science ®Google Scholar
• Wang Y, Zheng Y, Zhang L, et al. Stability of nanosuspensions in drug delivery. J Control Release. 2013;172(3):1126–1141.
   PubMed Web of Science ®Google Scholar
• Verma S, Kumar S, Gokhale R, et al. Physical stability of nanosuspensions: investigation of the role of stabilizers on Ostwald ripening. Int J Pharm. 2011;406(1):145–152.
   PubMed Web of Science ®Google Scholar
• Ghosh I, Bose S, Vippagunta R, et al. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int J Pharm. 2011;409(1):260–268.
   PubMedGoogle Scholar
• Nagarwal RC, Kumar R, Dhanawat M, et al. Nanocrystal technology in the delivery of poorly soluble drugs: an overview. Curr Drug Deliv. 2011;8(4):398–406.
   PubMed Web of Science ®Google Scholar
• Lohani A, Verma A, Joshi H, et al. Nanotechnology-based cosmeceuticals. ISRN Dermatol. 2014;2014:1-14.
   Google Scholar
• Lai F, Pireddu R, Corrias F, et al. Nanosuspension improves tretinoin photostability and delivery to the skin. Int J Pharm. 2013;458(1):104–109.
   PubMedGoogle Scholar
• Hatahet T, Morille M, Hommoss A, et al. Dermal quercetin smartCrystals®: formulation development, antioxidant activity and cellular safety. Eur J Pharm Biopharm. 2016;102:51–63.
   PubMed Web of Science ®Google Scholar
• Gao L, Gan H, Meng Z, et al. Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals. Colloids Surf B Biointer. 2016;148:343–353.
   PubMed Web of Science ®Google Scholar
• Romero GB, Arntjen A, Keck CM, et al. Amorphous cyclosporin A nanoparticles for enhanced dermal bioavailability. Int J Pharm. 2016;498(1):217–224.
   PubMedGoogle Scholar
• Ghosh I, Michniak-Kohn B. Influence of critical parameters of nanosuspension formulation on the permeability of a poorly soluble drug through the skin—a case study. AAPS PharmSciTech. 2013;14(3):1108–1117.
   PubMed Web of Science ®Google Scholar
• Pireddu R, Caddeo C, Valenti D, et al. Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability. Colloids Surf B Biointer. 2016;143:64–70.
   PubMed Web of Science ®Google Scholar
• Pireddu R, Sinico C, Ennas G, et al. Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability. Eur J Pharm Sci. 2015;77:208–215.
   PubMed Web of Science ®Google Scholar
• Sinico C, Pireddu R, Pini E, et al. Enhancing topical delivery of resveratrol through a nanosizing approach. Planta Medica. 2016;83(5):476-481.
   PubMed Web of Science ®Google Scholar
• Döge N, Hönzke S, Schumacher F, et al. Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin-assessment by intradermal microdialysis and extraction from the different skin layers. J Control Release. 2016;242:25–34.
   PubMed Web of Science ®Google Scholar
• Pyo SM, Meinke M, Keck CM, et al. Rutin—increased antioxidant activity and skin penetration by nanocrystal technology (smartCrystals). Cosmetics. 2016;3(1):9.
   Google Scholar
• Vidlářová L, Romero GB, Hanuš J, et al. Nanocrystals for dermal penetration enhancement–effect of concentration and underlying mechanisms using curcumin as model. Eur J Pharm Biopharm. 2016;104:216–225.
   PubMed Web of Science ®Google Scholar
• Colombo M, Staufenbiel S, Rühl E, et al. In situ determination of the saturation solubility of nanocrystals of poorly soluble drugs for dermal application. Int J Pharm. 2017;521(1):156–166.
   PubMedGoogle Scholar
• Wang W, Hu J, Sui H, et al. Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation. Die Pharmazie Int J Pharm Sci. 2016;71(5):252–257.
   Google Scholar
• Mishra PR, Al Shaal L, Müller RH, et al. Production and characterization of Hesperetin nanosuspensions for dermal delivery. Int J Pharm. 2009;371(1):182–189.
   PubMedGoogle Scholar
• Teeranachaideekul V, Junyaprasert VB, Souto EB, et al. Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology. Int J Pharm. 2008;354(1):227–234.
   PubMedGoogle Scholar
• Zhai X, Lademann J, Keck CM, et al. Dermal nanocrystals from medium soluble actives–physical stability and stability affecting parameters. Eur J Pharm Biopharm. 2014;88(1):85–91.
   PubMed Web of Science ®Google Scholar
• Corp NP. SILCRYST™ medical dressings.[ cited 2018 Feb 8]. Available from: http://www.nucryst.com/silcryst_division.htm
   Google Scholar
• Kumari K, Sharma PK, Gupta R. Nano-cosmeceuticals: an emerging novel trend towards dermal care. Adv Cosmetics Dermatol. 2017;03(01):01–12.
   Google Scholar
• Medicine UNLo. Comparative analysis of cost-effectiveness of silver dressing in burns (ARGENTUM). 2016 [cited 2018 Feb 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT02108535?term=nano+AND+crystalline&draw=2&rank=11
   Google Scholar
• Medicine UNLo. Pilot study - putative penetration of nanoparticles in sunscreen in intact or sunburned skin. 2012 [cited 2018 Feb 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT01552135?term=nano+AND+nanoparticle&rank=8
   Google Scholar
• Medicine UNLo. Efficacy of silver nanoparticle Gel versus a common antibacterial hand Gel. 2008 [cited 2018 Feb 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT00659204?term=nano+AND+nanoparticle&rank=10
   Google Scholar
• Medicine UNLo. Nanoparticulate versus micronized steroids delivery for transdermal hormone replacement therapy (Nanoparticle). 2016 [cited 2018 Feb 8]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02467673?term=nano+AND+nano+particles&draw=2&rank=13
   Google Scholar
• Gupta N, Bedi S, Srivastava J, et al, inventor; Sun Pharmaceutical Industries Ltd., assignee. Topical pharmaceutical composition comprising nanonized silver sulfadiazine. US9572777B2. 2014. .
   Google Scholar
• Keith Johnson RL, Mei Y, Holly M, et al, inventor; Dfb Soria, Llc, assignee. Delivery of drug nanoparticles and methods of use thereof. WO2017049083 A3. 2017.
   Google Scholar
• Petersson K, inventor; Leo Pharma AS, assignee. Calcipotriol monohydrate nanocrystals. US20140322331. 2014.
   Google Scholar
• Tapley CAM, inventor; Tioxide Specialties Ltd., assignee. Method of preparing sunscreens. EP0535972B1. 1993.
   Google Scholar
• Lange CEDM, inventor. Topical care products or medicines containing finely divided transparent zinc oxide. DE4232143A1.1994.
   Google Scholar
• Vergnault G, Grenier P, Nhamias A, et al, inventor; Jagotec AG, assignee. Topical nanoparticulate spironolactone formulation. US8003690. 2011.
   Google Scholar