Abstract
The exploration of nanocrystal technology is currently receiving significant attention in various fields, including therapeutic formulation, clinical formulation, in-vivo and in-vitro correlation research, and related investigations. The domain of nanocrystals in pharmaceutical delivery has received significant interest as a potential solution for the difficulties associated with medications that have low solubility. The nanocrystals demonstrate promise in improving solubility and bioavailability, presenting a potential resolution to significant challenges. Significantly, nanocrystals have exhibited efficacy in the context of oral administration, showcasing prompt absorption due to their quick breakdown, hence fitting with the requirements of medications that necessitate fast commencement of action. In addition, the adaptability of drug nanocrystals encompasses several methods of administration, including oral, parenteral, ophthalmic, cutaneous, pulmonary, and targeted delivery modalities. The observed consistency can be ascribed to the increased solubility of nanocrystals of the medicine, which effectively counteracts the influence of food on the absorption of the drug. Surface modification tactics have a significant influence on insoluble medicines by enhancing hydrophilicity and reducing plasma protein adsorption on the crystal surface. The surface properties of nanocrystals are modified through the utilization of specific surfactants and polymers, which are subsequently incorporated into polymer solutions via high-pressure homogenization procedures. This article encompasses an examination of the drug distribution mechanism, the nanocrystal formulation technology, the therapeutic applications, the potential future developments, and the challenges associated with the solubility and bioavailability of tailored nanocrystals, as discussed in this article. Consequently, it possesses the capacity to provide guidance for future investigations pertaining to nanocrystal technology.
Graphical Abstract
[1]
Nagarwal RC, Kumar R, Dhanawat M, Das N, Pandit JK. Nanocrystal technology in the delivery of poorly soluble drugs: an overview. Curr Drug Deliv 2011; 8(4): 398-406.
[http://dx.doi.org/10.2174/156720111795767988] [PMID: 21453258]
[http://dx.doi.org/10.2174/156720111795767988] [PMID: 21453258]
[2]
Joshi K, Chandra A, Jain K. Talegaonkar SJPn. Nanocrystalization: an emerging technology to enhance the bioavailability of poorly soluble drugs. Pharm Nanotechnol 2019; 7(4): 259-78.
[3]
Junyaprasert VB. Morakul BJajops. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci 2015; 10(1): 13-23.
[http://dx.doi.org/10.1016/j.ajps.2014.08.005]
[http://dx.doi.org/10.1016/j.ajps.2014.08.005]
[4]
Fernandes AR, Dias-Ferreira J, Ferreira-da-Silva C, Severino P, Martins-Gomes C, Silva AM, et al. Drug nanocrystals: Present, past and future. In: applications of nanocomposite materials in drug delivery. Elsevier 2018; pp. 239-53.
[http://dx.doi.org/10.1016/B978-0-12-813741-3.00011-X]
[http://dx.doi.org/10.1016/B978-0-12-813741-3.00011-X]
[5]
Thipparaboina R, Chavan RB, Shastri NR. Nanocrystals for delivery of therapeutic agents. In: particulate technology for delivery of therapeutics. Springer 2017; pp. 291-316.
[http://dx.doi.org/10.1007/978-981-10-3647-7_9]
[http://dx.doi.org/10.1007/978-981-10-3647-7_9]
[6]
Saini JK, Kumar S. Development of nanocrystal formulation with improved dissolution. J Drug Deliv Ther 2018; 8(5): 118-29.
[http://dx.doi.org/10.22270/jddt.v8i5.1946]
[http://dx.doi.org/10.22270/jddt.v8i5.1946]
[7]
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 Nanopart Res 2008; 10(5): 845-62.
[http://dx.doi.org/10.1007/s11051-008-9357-4]
[http://dx.doi.org/10.1007/s11051-008-9357-4]
[8]
Zhou Y, Du J, Wang L, Wang YJ. State of the art of nanocrystals technology for delivery of poorly soluble drugs. J Nanopart Res 2016; 18(9): 257.
[9]
Fontana F, Figueiredo P, Zhang P, Hirvonen JT, Liu D, Santos HAJ. Production of pure drug nanocrystals and nano co-crystals by confinement methods. Adv Drug Deliv Rev 2018; 131: 3-21.
[http://dx.doi.org/10.1016/j.addr.2018.05.002]
[http://dx.doi.org/10.1016/j.addr.2018.05.002]
[10]
Shegokar R, Müller RHJ. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm 2010; 399(1-2): 129-39.
[11]
Mohammad IS, Hu H, Yin L, He WJ. Drug nanocrystals: fabrication methods and promising therapeutic applications. Int J Pharm 2019; 562: 187-202.
[12]
Sharma OP, Patel V, Mehta TJ. Nanocrystal for ocular drug delivery: hope or hype. Drug Deliv Transl Res 2016; 6(4): 399-413.
[13]
Malamatari M, Taylor KM, Malamataris S, Douroumis D, Kachrimanis KJ. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov Today 2018; 23(3): 534-47.
[http://dx.doi.org/10.1016/j.drudis.2018.01.016]
[http://dx.doi.org/10.1016/j.drudis.2018.01.016]
[14]
Bansal S, Bansal M, Kumria RJ. Nanocrystals: current strategies and trends. Int J Res Pharm Biomed Sci 2012; 4: 10.
[15]
Pawar VK, Singh Y, Meher JG, Gupta S, Chourasia MKJ. Engineered nanocrystal technology: in-vivo fate, targeting and applications in drug delivery. J Control Release 2014; 183: 51-66.
[16]
Sawant SV, Kadam D, Jadhav D, Sankpal SVJIJSID. Drug nanocrystals: novel technique for delivery of poorly soluble drugs. Int J Sci Res Innov 2011; 1: 1-15.
[17]
Zhou Y, Du J, Wang L, Wang YJ. Nanocrystals technology for improving bioavailability of poorly soluble drugs: a mini-review. J Nanosci Nanotechnol 2017; 17(1): 18-28.
[18]
Sun B, Yeo Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr Opin Solid State Mater Sci 2012; 16(6): 295-301.
[19]
Chen Z, Wu W, Lu Y. What is the future for nanocrystal-based drug-delivery systems? Ther Deliv 2020; 11(4): 225-9.
[http://dx.doi.org/10.4155/tde-2020-0016] [PMID: 32157960]
[http://dx.doi.org/10.4155/tde-2020-0016] [PMID: 32157960]
[20]
Gigliobianco M, Casadidio C, Censi R, Di Martino P. Nanocrystals of poorly soluble drugs: drug bioavailability and physicochemical stability. Pharmaceutics 2018; 10(3): 134.
[http://dx.doi.org/10.3390/pharmaceutics10030134] [PMID: 30134537]
[http://dx.doi.org/10.3390/pharmaceutics10030134] [PMID: 30134537]
[21]
Bhuyan B, Rajak P, Nath L. Nanocrystal technology and drug delivery. World J Pharm Res 2014; 3: 2940-71.
[22]
Jarvis M, Krishnan V, Mitragotri S. Nanocrystals: A perspective on translational research and clinical studies. Bioeng Transl Med 2019; 4(1): 5-16.
[http://dx.doi.org/10.1002/btm2.10122] [PMID: 30680314]
[http://dx.doi.org/10.1002/btm2.10122] [PMID: 30680314]
[23]
Junghanns JU, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine 2008; 3(3): 295-309.
[PMID: 18990939]
[PMID: 18990939]
[24]
Sajanlal PR, Sreeprasad TS, Samal AK, Pradeep T. Anisotropic nanomaterials: structure, growth, assembly, and functions. Nano Rev 2011; 2(1): 5883.
[http://dx.doi.org/10.3402/nano.v2i0.5883] [PMID: 22110867]
[http://dx.doi.org/10.3402/nano.v2i0.5883] [PMID: 22110867]
[26]
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): 307-24.
[http://dx.doi.org/10.1007/s11095-012-0889-z] [PMID: 23073665]
[http://dx.doi.org/10.1007/s11095-012-0889-z] [PMID: 23073665]
[27]
Shah R, Eldridge D, Palombo E, Harding I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. J Physiol Sci 2014; 25(1)
[28]
Haddad R, Alrabadi N, Altaani B, Li T. Paclitaxel drug delivery systems: focus on nanocrystals’ surface modifications. Polymers (Basel) 2022; 14(4): 658.
[http://dx.doi.org/10.3390/polym14040658] [PMID: 35215570]
[http://dx.doi.org/10.3390/polym14040658] [PMID: 35215570]
[29]
Permana AD, Utami RN, Layadi P, et al. Thermosensitive and mucoadhesive in situ ocular gel for effective local delivery and antifungal activity of itraconazole nanocrystal in the treatment of fungal keratitis. Int J Pharm 2021; 602: 120623.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120623] [PMID: 33892058]
[http://dx.doi.org/10.1016/j.ijpharm.2021.120623] [PMID: 33892058]
[30]
Parveen N, Abourehab MAS, Thanikachalam PV, Khar RK, Kesharwani P. Nanocrystals as an emerging nanocarrier for the management of dermatological diseases. Colloids Surf B Biointerfaces 2023; 225: 113231.
[http://dx.doi.org/10.1016/j.colsurfb.2023.113231] [PMID: 36907135]
[http://dx.doi.org/10.1016/j.colsurfb.2023.113231] [PMID: 36907135]
[31]
Melo KJC, Henostroza MAB, Löbenberg R, Bou-Chacra NA. Rifampicin nanocrystals: Towards an innovative approach to treat tuberculosis. Mater Sci Eng C 2020; 112: 110895.
[http://dx.doi.org/10.1016/j.msec.2020.110895] [PMID: 32409052]
[http://dx.doi.org/10.1016/j.msec.2020.110895] [PMID: 32409052]
[32]
Torrado-Salmerón C, Guarnizo-Herrero V, Henriques J, Seiça R, Sena CM, Torrado-Santiago S. Multiparticulate systems of ezetimibe micellar system and atorvastatin solid dispersion efficacy of low-dose ezetimibe/atorvastatin on high-fat diet-induced hyperlipidemia and hepatic steatosis in diabetic rats. Pharmaceutics 2021; 13(3): 421.
[http://dx.doi.org/10.3390/pharmaceutics13030421] [PMID: 33804727]
[http://dx.doi.org/10.3390/pharmaceutics13030421] [PMID: 33804727]
[33]
Cavassin FB, Baú-Carneiro JL, Vilas-Boas RR, Queiroz-Telles F. Sixty years of amphotericin B: an overview of the main antifungal agent used to treat invasive fungal infections. Infect Dis Ther 2021; 10(1): 115-47.
[http://dx.doi.org/10.1007/s40121-020-00382-7] [PMID: 33523419]
[http://dx.doi.org/10.1007/s40121-020-00382-7] [PMID: 33523419]
[34]
Liu Z, Li S, Xia X, Zhu Z, Chen L, Chen Z. Recent advances in multifunctional graphitic nanocapsules for Raman detection, imaging, and therapy. Small Methods 2020; 4(4): 1900440.
[http://dx.doi.org/10.1002/smtd.201900440]
[http://dx.doi.org/10.1002/smtd.201900440]
[35]
Chandler M, Panigaj M, Rolband LA, Afonin KA. Challenges in optimizing RNA nanostructures for large-scale production and controlled therapeutic properties. Nanomedicine (Lond) 2020; 15(13): 1331-40.
[http://dx.doi.org/10.2217/nnm-2020-0034] [PMID: 32452262]
[http://dx.doi.org/10.2217/nnm-2020-0034] [PMID: 32452262]
[36]
Liu C, Zeng Q, Wei H, et al. Metal halide perovskite nanocrystal solar cells: progress and challenges. Small Methods 2020; 4(10): 2000419.
[http://dx.doi.org/10.1002/smtd.202000419]
[http://dx.doi.org/10.1002/smtd.202000419]
[37]
Udhayakumar M, Radhika N, Arun KL. A comprehensive review on nanocrystalline coatings: properties, challenges and applications. J Bio Tribocorros 2022; 8(3): 83.
[http://dx.doi.org/10.1007/s40735-022-00683-z]
[http://dx.doi.org/10.1007/s40735-022-00683-z]
[38]
Pedroso CCS, Mann VR, Zuberbühler K, et al. Immunotargeting of nanocrystals by SpyCatcher conjugation of engineered antibodies. ACS Nano 2021; 15(11): 18374-84.
[http://dx.doi.org/10.1021/acsnano.1c07856] [PMID: 34694776]
[http://dx.doi.org/10.1021/acsnano.1c07856] [PMID: 34694776]
[39]
Mourdikoudis S, Pallares RM, Thanh NTK. Characterization techniques for nanoparticles: comparison and complementarity upon studying nanoparticle properties. Nanoscale 2018; 10(27): 12871-934.
[http://dx.doi.org/10.1039/C8NR02278J] [PMID: 29926865]
[http://dx.doi.org/10.1039/C8NR02278J] [PMID: 29926865]
[40]
Gülsün T, Gürsoy RN, Öner L. Nanocrystal technology for oral delivery of poorly water-soluble drugs. FABAD Journal of Pharmaceutical Sciences 2009; 34(1): 55.
[41]
Mittal P, Dhankhar S, Chauhan S, et al. A review on natural antioxidants for their role in the treatment of parkinson’s disease. Pharmaceuticals (Basel) 2023; 16(7): 908.
[http://dx.doi.org/10.3390/ph16070908] [PMID: 37513820]
[http://dx.doi.org/10.3390/ph16070908] [PMID: 37513820]
[42]
Shankar SJ, Jaswanth Gowda BH, Akshatha RS, Metikurki B, Rehamathulla M. A review on the role of nanocrystals and nanosuspensions in drug delivery systems. Int J Appl Pharm 2020; pp. 10-6.
[43]
Salazar J, Müller RH, Möschwitzer JP. Combinative particle size reduction technologies for the production of drug nanocrystals. J Pharm (Cairo) 2014; 2014: 1-14.
[http://dx.doi.org/10.1155/2014/265754] [PMID: 26556191]
[http://dx.doi.org/10.1155/2014/265754] [PMID: 26556191]
[44]
de Waard H, Frijlink HW, Hinrichs WLJ. Bottom-up preparation techniques for nanocrystals of lipophilic drugs. Pharm Res 2011; 28(5): 1220-3.
[http://dx.doi.org/10.1007/s11095-010-0323-3] [PMID: 21086152]
[http://dx.doi.org/10.1007/s11095-010-0323-3] [PMID: 21086152]
[45]
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): 126-41.
[http://dx.doi.org/10.1016/j.ijpharm.2013.01.019] [PMID: 23333709]
[http://dx.doi.org/10.1016/j.ijpharm.2013.01.019] [PMID: 23333709]
[46]
Mu RH. Manufacturing of nanoparticles by milling and homogenization techniques. Nanoparticle technology for drug delivery 2006; 45-76.
[47]
Singh TG, Dhiman S, Rehni AK. Formulation and evaluation of nanopharmaceuticals in drug delivery. Future Science Ltd. 2013.
[http://dx.doi.org/10.4155/ebo.13.398]
[http://dx.doi.org/10.4155/ebo.13.398]
[48]
Singh TG, Sharma N. Nanobiomaterials in cosmetics: current status and future prospects.In: Nanobiomaterials in Galenic Formulations and Cosmetics. 2016; pp. 149-74.
[http://dx.doi.org/10.1016/B978-0-323-42868-2.00007-3]
[http://dx.doi.org/10.1016/B978-0-323-42868-2.00007-3]
[49]
Dhiman S, Singh TG, Asthana A, Arora S, Jindal M. Solid lipid nanoparticles: a current approach to new drug-delivery systems in nanotechnology. Future Science Ltd. 2013.
[50]
Wadhwa K, Kadian V, Puri V, et al. New insights into quercetin nanoformulations for topical delivery. Phytomedicine Plus 2022; 2(2): 100257.
[http://dx.doi.org/10.1016/j.phyplu.2022.100257]
[http://dx.doi.org/10.1016/j.phyplu.2022.100257]
[51]
Kumari Y, Singh SK, Kumar R, et al. Modified apple polysaccharide capped gold nanoparticles for oral delivery of insulin. Int J Biol Macromol 2020; 149: 976-88.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.302] [PMID: 32018009]
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.302] [PMID: 32018009]
[52]
Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lipid nanocarriers for dermal delivery of lutein: Preparation, characterization, stability and performance. Int J Pharm 2011; 414(1-2): 267-75.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.008] [PMID: 21596122]
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.008] [PMID: 21596122]
[53]
Gao L, Liu G, Ma J, Wang X, Zhou L, Li X. Drug nanocrystals: In vivo performances. J Control Release 2012; 160(3): 418-30.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.013] [PMID: 22465393]
[http://dx.doi.org/10.1016/j.jconrel.2012.03.013] [PMID: 22465393]
[54]
Lin N, Huang J, Dufresne A. Preparation, properties and applications of polysaccharide nanocrystals in advanced functional nanomaterials: a review. Nanoscale 2012; 4(11): 3274-94.
[http://dx.doi.org/10.1039/c2nr30260h] [PMID: 22565323]
[http://dx.doi.org/10.1039/c2nr30260h] [PMID: 22565323]
[55]
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]
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720]
[56]
Liu J, Gong T, Wang C, Zhong Z, Zhang Z. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: Preparation and characterization. Int J Pharm 2007; 340(1-2): 153-62.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.009] [PMID: 17428627]
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.009] [PMID: 17428627]
