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2000
Volume 15, Issue 5
  • ISSN: 2468-1873
  • E-ISSN: 2468-1881

Abstract

Nanocrystals, composed of a few hundred to tens of thousands of atoms, coalesce to form crystalline clusters, revolutionizing the landscape of pharmaceutical compounds. These clusters, often referred to as “clusters,” serve as crystalline structures that wield significant influence over the pharmacokinetic and pharmacodynamic characteristics of diverse pharmacological agents. Employed for various applications, nanocrystals play a pivotal role in safeguarding drug entities during systemic circulation within the body. The production of nanocrystals employs diverse methodologies, including spray drying, top-down approaches, bottom-up strategies, and innovative techniques. The formulation of nanocrystals yields a spectrum of advantages, such as augmenting oral bioavailability, optimizing dose proportionality, mitigating food-related effects, ensuring suitability for administration through diverse routes, and enabling sterile filtration due to a more confined particle size range. The selection of the appropriate method is contingent upon the specific target sites and the drug's capacity to reach the intended site of action consistently and at a controlled rate. This exploration delves into several facets of nanocrystals in drug delivery, shedding light on their multifaceted uses within the pharmaceutical realm.

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2024-06-13
2025-10-11
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References

  1. FontanaF. FigueiredoP. ZhangP. HirvonenJ.T. LiuD. SantosH.A. Production of pure drug nanocrystals and nano co-crystals by confinement methods.Adv. Drug Deliv. Rev.201813132110.1016/j.addr.2018.05.00229738786
    [Google Scholar]
  2. JacobS. NairA.B. ShahJ. Emerging role of nanosuspensions in drug delivery systems.Biomater. Res.2020241310.1186/s40824‑020‑0184‑831969986
    [Google Scholar]
  3. ZielińskaA. CarreiróF. OliveiraA.M. NevesA. PiresB. VenkateshD.N. DurazzoA. LucariniM. EderP. SilvaA.M. SantiniA. SoutoE.B. Polymeric nanoparticles: Production, characterization, toxicology and ecotoxicology.Molecules20202516373110.3390/molecules2516373132824172
    [Google Scholar]
  4. DateA.A. HanesJ. EnsignL.M. Nanoparticles for oral delivery: Design, evaluation and state-of-the-art.J. Control. Release201624050452610.1016/j.jconrel.2016.06.01627292178
    [Google Scholar]
  5. ZhangL. RodriguezJ. RaezJ. MylesA.J. FenniriH. WebsterT.J. Biologically inspired rosette nanotubes and nanocrystalline hydroxyapatite hydrogel nanocomposites as improved bone substitutes.Nanotechnology2009201717510110.1088/0957‑4484/20/17/17510119420581
    [Google Scholar]
  6. DuanY. DharA. PatelC. KhimaniM. NeogiS. SharmaP. Siva KumarN. VekariyaR.L. A brief review on solid lipid nanoparticles: Part and parcel of contemporary drug delivery systems.RSC Advances20201045267772679110.1039/D0RA03491F35515778
    [Google Scholar]
  7. GaoL. LiuG. MaJ. WangX. ZhouL. LiX. WangF. Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs.Pharm. Res.201330230732410.1007/s11095‑012‑0889‑z23073665
    [Google Scholar]
  8. LuY. LiY. WuW. Injected nanocrystals for targeted drug delivery.Acta Pharm. Sin. B20166210611310.1016/j.apsb.2015.11.00527006893
    [Google Scholar]
  9. LuY. ChenY. GemeinhartR.A. WuW. LiT. Developing nanocrystals for cancer treatment.Nanomedicine201510162537255210.2217/nnm.15.7326293310
    [Google Scholar]
  10. FuhrmannK. PołomskaA. AeberliC. CastagnerB. GauthierM.A. LerouxJ.C. Modular design of redox-responsive stabilizers for nanocrystals.ACS Nano2013798243825010.1021/nn403731723968310
    [Google Scholar]
  11. MüllerR.H. GohlaS. KeckC.M. State of the art of nanocrystals – Special features, production, nanotoxicology aspects and intracellular delivery.Eur. J. Pharm. Biopharm.20117811910.1016/j.ejpb.2011.01.00721266197
    [Google Scholar]
  12. RomeroG.B. ArntjenA. KeckC.M. MüllerR.H. Amorphous cyclosporin A nanoparticles for enhanced dermal bioavailability.Int. J. Pharm.20164981-221722410.1016/j.ijpharm.2015.12.01926688038
    [Google Scholar]
  13. SharmaO.P. PatelV. MehtaT. Nanocrystal for ocular drug delivery: Hope or hype.Drug Deliv. Transl. Res.20166439941310.1007/s13346‑016‑0292‑027165145
    [Google Scholar]
  14. PawarV.K. SinghY. MeherJ.G. GuptaS. ChourasiaM.K. Engineered nanocrystal technology: in-vivo fate, targeting and applications in drug delivery.J. Control. Release2014183516610.1016/j.jconrel.2014.03.03024667572
    [Google Scholar]
  15. GaoL. LiuG. MaJ. WangX. ZhouL. LiX. Drug nanocrystals: in vivo performances.J. Control. Release2012160341843010.1016/j.jconrel.2012.03.01322465393
    [Google Scholar]
  16. LiJ. WangZ. ZhangH. GaoJ. ZhengA. Progress in the development of stabilization strategies for nanocrystal preparations.Drug Deliv.2021281193610.1080/10717544.2020.185622433336609
    [Google Scholar]
  17. JoshiK. ChandraA. JainK. TalegaonkarS. Nanocrystalization: An emerging technology to enhance the bioavailability of poorly soluble drugs.Pharm. Nanotechnol.20197425927810.2174/221173850766619040518252430961518
    [Google Scholar]
  18. GigliobiancoM. CasadidioC. CensiR. Di MartinoP. Nanocrystals of poorly soluble drugs: Drug bioavailability and physicochemical stability.Pharmaceutics201810313410.3390/pharmaceutics1003013430134537
    [Google Scholar]
  19. KalepuS. NekkantiV. Insoluble drug delivery strategies: Review of recent advances and business prospects.Acta Pharm. Sin. B20155544245310.1016/j.apsb.2015.07.00326579474
    [Google Scholar]
  20. MisraS.K. PathakK. Supercritical fluid technology for solubilization of poorly water soluble drugs via micro- and naonosized particle generation.ADMET DMPK20208435537410.5599/admet.81135300190
    [Google Scholar]
  21. KankalaR. ChenB.Q. LiuC.G. TangH.X. WangS.B. ChenA.Z. Solution-enhanced dispersion by supercritical fluids: An ecofriendly nanonization approach for processing biomaterials and pharmaceutical compounds.Int. J. Nanomedicine2018134227424510.2147/IJN.S16612430087558
    [Google Scholar]
  22. BhalaniD.V. NutanB. KumarA. Singh ChandelA.K. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics.Biomedicines2022109205510.3390/biomedicines1009205536140156
    [Google Scholar]
  23. DegobertG. AydinD. Lyophilization of nanocapsules: Instability sources, formulation and process parameters.Pharmaceutics2021138111210.3390/pharmaceutics1308111234452072
    [Google Scholar]
  24. El-EskandaranyM.S. Al-HazzaA. Al-HajjiL.A. AliN. Al-DuweeshA.A. BanyanM. Al-AjmiF. Mechanical milling: A superior nanotechnological tool for fabrication of nanocrystalline and nanocomposite materials.Nanomaterials20211110248410.3390/nano1110248434684925
    [Google Scholar]
  25. KavinilaS. NimbkarS. MosesJ.A. AnandharamakrishnanC. Emerging applications of microfluidization in the food industry.J. Agric. Res.202312100537
    [Google Scholar]
  26. RanQ. WangM. KuangW. OuyangJ. HanD. GaoZ. GongJ. Advances of combinative nanocrystal preparation technology for improving the insoluble drug solubility and bioavailability.Crystals2022129120010.3390/cryst12091200
    [Google Scholar]
  27. ChauhanI. YasirM. VermaM. SinghA.P. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery.Adv. Pharm. Bull.202010215016510.34172/apb.2020.02132373485
    [Google Scholar]
  28. AhmedT. Preparation of finasteride capsules-loaded drug nanoparticles: Formulation, optimization, in vitro, and pharmacokinetic evaluation.Int. J. Nanomedicine20161151552710.2147/IJN.S9808026893559
    [Google Scholar]
  29. DamianF. HaratiM. SchwartzenhauerJ. Van CauwenbergheO. WettigS.D. Challenges of dissolution methods development for soft gelatin capsules.Pharmaceutics202113221410.3390/pharmaceutics1302021433557167
    [Google Scholar]
  30. TadauchiT. YamadaD. KoideY. YamadaM. ShimadaY. YamazoeE. ItoT. TaharaK. Improving the powder properties of an active pharmaceutical ingredient (Ethenzamide) with a silica nanoparticle coating for direct compaction into tablets.Powders20221423124210.3390/powders1040016
    [Google Scholar]
  31. MaY. CongZ. GaoP. WangY. Nanosuspensions technology as a master key for nature products drug delivery and in vivo fate.Eur. J. Pharm. Sci.202318510642510.1016/j.ejps.2023.10642536934992
    [Google Scholar]
  32. MominM.A.M. TuckerI.G. DoyleC.S. DenmanJ.A. DasS.C. Manipulation of spray-drying conditions to develop dry powder particles with surfaces enriched in hydrophobic material to achieve high aerosolization of a hygroscopic drug.Int. J. Pharm.20185431-231832710.1016/j.ijpharm.2018.04.00329626509
    [Google Scholar]
  33. SambhakarS. Nanoemulsion: An emerging novel technology for improving the bioavailability of drugs.Scientifica202320236640103
    [Google Scholar]
  34. PınarS.G. OktayA.N. KaraküçükA.E. ÇelebiN. Formulation strategies of nanosuspensions for various administration routes.Pharmaceutics2023155152010.3390/pharmaceutics1505152037242763
    [Google Scholar]
  35. AldeebM. WilarG. SuhandiC. ElaminK. WathoniN. Nanosuspension-based drug delivery systems for topical applications.Int. J. Nanomedicine20241982584410.2147/IJN.S44742938293608
    [Google Scholar]
  36. Ahmadi TehraniA. OmranpoorM.M. VatanaraA. SeyedabadiM. RamezaniV. Formation of nanosuspensions in bottom-up approach: Theories and optimization.Daru201927145147310.1007/s40199‑018‑00235‑230661188
    [Google Scholar]
  37. KumarM. VirmaniT. KumarG. DeshmukhR. SharmaA. DuarteS. BrandãoP. FonteP. Nanocarriers in tuberculosis treatment: Challenges and delivery strategies.Pharmaceuticals20231610136010.3390/ph1610136037895831
    [Google Scholar]
  38. HeS. GuiJ. XiongK. ChenM. GaoH. FuY. A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases.J. Nanobiotechnology202220110110.1186/s12951‑022‑01307‑x35241085
    [Google Scholar]
  39. PengS. WangW. ZhangR. WuC. PanX. HuangZ. Nano-formulations for pulmonary delivery: Past, present, and future perspectives.Pharmaceutics202416216110.3390/pharmaceutics1602016138399222
    [Google Scholar]
  40. YuY.Q. YangX. WuX.F. FanY.B. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: Novel strategies for effective transdermal applications.Front. Bioeng. Biotechnol.2021964655410.3389/fbioe.2021.64655433855015
    [Google Scholar]
  41. MundeM.K. ShindeA.M. KulkarniN.S. TambeV.S. AlhatH.P. Comprehensive review on nanocrystal technology in pharmaceutical formulations.Int. J. Pharm. Pharm. Sci.2023151710.22159/ijpps.2023v15i4.47317
    [Google Scholar]
  42. FytianosG. RahdarA. KyzasG.Z. Nanomaterials in cosmetics: Recent updates.Nanomaterials202010597910.3390/nano1005097932443655
    [Google Scholar]
  43. WuK.Y. TanK. AkbarD. ChoulakianM.Y. TranS.D. A new era in ocular therapeutics: Advanced drug delivery systems for uveitis and neuro-ophthalmologic conditions.Pharmaceutics2023157195210.3390/pharmaceutics1507195237514137
    [Google Scholar]
  44. GargalloC.J. SostresC. LanasA. Prevention and treatment of NSAID gastropathy.Curr. Treat. Options Gastroenterol.201412439841310.1007/s11938‑014‑0029‑425209136
    [Google Scholar]
  45. SanasM.N. PachputeT.S. Exploring the potential of ketoprofen nanosuspension: in vitro and in vivo insights into drug release and bioavailability.J. Drug Deliv. Ther.202313615215810.22270/jddt.v13i6.5890
    [Google Scholar]
  46. MüllerR.H. JacobsC. Buparvaquone mucoadhesive nanosuspension: Preparation, optimisation and long-term stability.Int. J. Pharm.20022371-215116110.1016/S0378‑5173(02)00040‑611955813
    [Google Scholar]
  47. MehrabianA. MashreghiM. DadpourS. BadieeA. ArabiL. Hoda AlavizadehS. Alia MoosavianS. Reza JaafariM. Nanocarriers call the last shot in the treatment of brain cancers.Technol. Cancer Res. Treat.20222110.1177/1533033822108097435253549
    [Google Scholar]
  48. PipernoA. SciortinoM.T. GiustoE. MontesiM. PanseriS. ScalaA. Recent advances and challenges in gene delivery mediated by polyester-based nanoparticles.Int. J. Nanomedicine2021165981600210.2147/IJN.S32132934511901
    [Google Scholar]
  49. SinghP. MuhammadI. NelsonN.E. TranK.T.M. VinikoorT. ChorsiM.T. D’OrioE. NguyenT.D. Transdermal delivery for gene therapy.Drug Deliv. Transl. Res.202212112613263310.1007/s13346‑022‑01138‑135538189
    [Google Scholar]
  50. BulchaJ.T. WangY. MaH. TaiP.W.L. GaoG. Viral vector platforms within the gene therapy landscape.Signal Transduct. Target. Ther.2021615310.1038/s41392‑021‑00487‑633558455
    [Google Scholar]
  51. ZengY. NixonR.L. LiuW. WangR. The applications of functionalized DNA nanostructures in bioimaging and cancer therapy.Biomaterials202126812056010.1016/j.biomaterials.2020.12056033285441
    [Google Scholar]
  52. LeN.B.T. TuA.T.T. ZhaoD. YoshikawaC. KawakamiK. KaizukaY. YamazakiT. Influence of the charge ratio of guanine-quadruplex structure-based CpG oligodeoxynucleotides and cationic DOTAP liposomes on cytokine induction profiles.Biomolecules20231311163910.3390/biom1311163938002321
    [Google Scholar]
  53. HigashiY. MatsumotoK. SaitohH. ShiroA. MaY. LairdM. ChinnathambiS. BiraultA. DoanT.L.H. YasudaR. TajimaT. KawachiT. TamanoiF. Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray.Sci. Rep.20211111419210.1038/s41598‑021‑93429‑934262055
    [Google Scholar]
  54. DongY. YaoC. ZhuY. YangL. LuoD. YangD. DNA functional materials assembled from branched DNA: Design, synthesis, and applications.Chem. Rev.2020120179420948110.1021/acs.chemrev.0c0029432672036
    [Google Scholar]
  55. ChengQ. WeiT. FarbiakL. JohnsonL.T. DilliardS.A. SiegwartD.J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing.Nat. Nanotechnol.202015431332010.1038/s41565‑020‑0669‑632251383
    [Google Scholar]
  56. EickhoffW.M. EngersD.A. MuellerK.R. Nanoparticulate NSAID compositions.U.S. Patent 95-385614, 55187381996
  57. BorkhatariaC. PatelD. BhagoraS. PatelN. PatelK. ManekR. Study of homogenization on media milling time in preparation of irbesartan nanosuspension and optimization using design of experiments (DoE).Futur. J. Pharm. Sci.2020618710.1186/s43094‑020‑00105‑2
    [Google Scholar]
  58. NagaiN. OgataF. OtakeH. KawasakiN. Oral administration system based on meloxicam nanocrystals: Decreased dose due to high bioavailability attenuates risk of gastrointestinal side effects.Pharmaceutics202012431310.3390/pharmaceutics1204031332244754
    [Google Scholar]
  59. YuanQ. WangY. SongR. HouX. YuK. ZhengJ. ZhangJ. PuX. HanJ. ZongL. Study on formulation, in vivo exposure, and passive targeting of intravenous itraconazole nanosuspensions.Front. Pharmacol.20191022510.3389/fphar.2019.0022530983994
    [Google Scholar]
  60. HouC.D. WangJ.X. LeY. ZouH.K. ZhaoH. Preparation of azithromycin nanosuspensions by reactive precipitation method.Drug Dev. Ind. Pharm.201238784885410.3109/03639045.2011.63039422092042
    [Google Scholar]
  61. ShubarH.M. LachenmaierS. HeimesaatM.M. LohmanU. MauludinR. MuellerR.H. FitznerR. BornerK. LiesenfeldO. SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood–brain barriers.J. Drug Target.201119211412410.3109/1061186100373399520367080
    [Google Scholar]
  62. SigfridssonK. RydbergH. StrimforsM. Nano- and microcrystals of griseofulvin subcutaneously administered to rats resulted in improved bioavailability and sustained release.Drug Dev. Ind. Pharm.20194591477148610.1080/03639045.2019.162876931260340
    [Google Scholar]
  63. AliH.S.M. HanafyA. AlqurshiA. Engineering of solidified glyburide nanocrystals for tablet formulation via loading of carriers: Downstream processing, characterization, and bioavailability.Int. J. Nanomedicine2019141893190610.2147/IJN.S19473430936692
    [Google Scholar]
  64. LiX. ChenW. LiuK. ZhangS. YangR. LiuK. LiD. HuangY. Oridonin sensitizes hepatocellular carcinoma to the anticancer effect of sorafenib by targeting the AKT pathway.Cancer Manag. Res.2020128081809110.2147/CMAR.S25748232982405
    [Google Scholar]
  65. ShengH. ZhangY. NaiJ. Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells.Pharm Biol.202058151852710.1080/13880209.2020.176716032501184
    [Google Scholar]
  66. WuH.T. ChuangY.H. LinH.C. HuT.C. TuY.J. ChienL.J. Immediate release formulation of inhaled beclomethasone dipropionate-hydroxypropyl-beta-cyclodextrin composite particles produced using supercritical assisted atomization.Polymers20221410211410.3390/polym1410211435631996
    [Google Scholar]
  67. AhireE. ThakkarS. DarshanwadM. MisraM. Parenteral nanosuspensions: A brief review from solubility enhancement to more novel and specific applications.Acta Pharm. Sin. B20188573375510.1016/j.apsb.2018.07.01130245962
    [Google Scholar]
  68. Martínez-JiménezC. Cruz-AngelesJ. VideaM. MartínezL. Co-amorphous simvastatin-nifedipine with enhanced solubility for possible use in combination therapy of hypertension and hypercholesterolemia.Molecules2018239216110.3390/molecules2309216130154310
    [Google Scholar]
  69. MuS. LiM. GuoM. YangW. WangY. LiJ. FuQ. HeZ. Spironolactone nanocrystals for oral administration: Different pharmacokinetic performances induced by stabilizers.Colloids Surf. B Biointerfaces2016147738010.1016/j.colsurfb.2016.07.05127490456
    [Google Scholar]
  70. GaberD.A. Nanoparticles of lovastatin: Design, optimization and in vivo evaluation.Int. J. Nanomedicine2020154225423610.2147/IJN.S24112032606674
    [Google Scholar]
  71. MehraniY. MorovatiS. TajikT. SarmadiS. BitarafA. SouraniZ. ShahverdiM. JavadiH. KakishJ.E. BridleB.W. KarimiK. Communication between mast cells and group 2 innate lymphoid cells in the skin.Cells202413546210.3390/cells1305046238474426
    [Google Scholar]
  72. PeiW. LiX. BiR. ZhangX. ZhongM. YangH. ZhangY. LvK. Exosome membrane-modified M2 macrophages targeted nanomedicine: Treatment for allergic asthma.J. Control. Release202133825326710.1016/j.jconrel.2021.08.02434418524
    [Google Scholar]
  73. KratzerB. HoferS. ZabelM. PicklW.F. All the small things: How virus-like particles and liposomes modulate allergic immune responses.Eur. J. Immunol.2020501173210.1002/eji.20184781031799700
    [Google Scholar]
  74. ScheiblhoferS. MachadoY. FeinleA. ThalhamerJ. HüsingN. WeissR. Potential of nanoparticles for allergen-specific immunotherapy – use of silica nanoparticles as vaccination platform.Expert Opin. Drug Deliv.201613121777178810.1080/17425247.2016.120389827321476
    [Google Scholar]
  75. SoniS.S. RodellC.B. Polymeric materials for immune engineering: Molecular interaction to biomaterial design.Acta Biomater.202113313915210.1016/j.actbio.2021.01.01633484909
    [Google Scholar]
  76. LiuQ. WangX. LiuX. KumarS. GochmanG. JiY. LiaoY.P. ChangC.H. SituW. LuJ. JiangJ. MeiK.C. MengH. XiaT. NelA.E. Use of polymeric nanoparticle platform targeting the liver to induce treg-mediated antigen-specific immune tolerance in a pulmonary allergen sensitization model.ACS Nano20191344778479410.1021/acsnano.9b0144430964276
    [Google Scholar]
  77. ShahgordiS. SankianM. YazdaniY. MashayekhiK. Hasan AyatiS. SadeghiM. SaeidiM. HashemiM. Immune responses modulation by curcumin and allergen encapsulated into PLGA nanoparticles in mice model of rhinitis allergic through sublingual immunotherapy.Int. Immunopharmacol.20208410652510.1016/j.intimp.2020.10652532361190
    [Google Scholar]
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