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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

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Front. Chem. Sci. Eng.    2015, Vol. 9 Issue (1) : 1-14    https://doi.org/10.1007/s11705-015-1509-3
REVIEW ARTICLE
Nanocrystal technology for drug formulation and delivery
Tzu-Lan CHANG1,Honglei ZHAN1,Danni LIANG2,Jun F. LIANG1,*()
1. Department of Chemistry, Chemical Biology, and Biomedical Engineering, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Hoboken, NJ 07030, USA
2. Stony Brook University School of Medicine, Stony Brook, NY 11794, USA
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Abstract

With the development of modern technology like high throughput screening, combinatorial chemistry and computer aid drug design, the drug discovery process has been dramatically accelerated. However, new drug candidates often exhibit poor aqueous or even organic medium solubility. Additionally, many of them may have low dissolution velocity and low oral bioavailability. Nanocrystal formulation sheds new light on advanced drug development. Due to small (nano- or micro- meters) sizes, the increased surface-volume ratio leads to dramatically enhanced drug dissolution velocity and saturation solubility. The simplicity in preparation and the potential for various administration routes allow drug nanocrystals to be a novel drug delivery system for specific diseases (i.e. cancer). In addition to the comprehensive review of different technologies and methods in drug nanocrystal preparation, suspension, and stabilization, we will also compare nano- and micro-sized drug crystals in pharmaceutical applications and discuss current nanocrystal drugs on the market and their limitations.
Keywords drug nanocrystal      nanotechnology      formulation      bioavailability      stabilizers      drug delivery     
Corresponding Author(s): Jun F. LIANG   
Online First Date: 01 April 2015    Issue Date: 07 April 2015
 Cite this article:   
Honglei ZHAN,Danni LIANG,Jun F. LIANG, et al. Nanocrystal technology for drug formulation and delivery[J]. Front. Chem. Sci. Eng., 2015, 9(1): 1-14.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-015-1509-3
https://academic.hep.com.cn/fcse/EN/Y2015/V9/I1/1
Fig.1  Transmission electron microscopy (TEM) images of (a) nanocrystals of paclitaxel, (b) the lyophilized and reconstituted nanoparticles of paclitaxel, and (c) nanocrystals of camptothecin (CPT) [7]
Fig.2  Schematic representation of the media milling process [8,9]
Techniques Advantages Disadvantages Size ranges
Wet ball milling (WBM) Drugs that are poorly soluble in both aqueous and organic media can be easily formulated into nanosuspensions; ease of scale-up and little batch-to-batch variation; narrow size distribution of the final nano-sized product; flexibility in handling the drug quantity, ranging from 1 to 400 mg·mL?1; low energy technique Residues from milling media; slow process; unstable 150–400 nm
High-pressure homogenization (HPH) Allow aseptic production of nanosuspensions for parenteral administration; universally applicable; easy down-stream processing; fast method; possibility for aqueous-free production; (the others are the same as the WBM) Prerequisite of micronized drug particles; prerequisite of suspension formation using high-speed mixers before subjecting it to homogenization; technique consumes high energy; requires experience in operation 40–500 nm
Tab.1  Characteristics of top-down technologies [9,12,22,23]
Techniques Advantages Disadvantages Size ranges
Hydrosol It can produce crystalline drug nanoparticles The drug has to be soluble in at least one solvent; the process involves organic solvents that need to be removed 100–400 nm
Nanomorph? The amorphous form has higher saturation solubility and a faster dissolution rate than the crystalline form Undesired compound recrystallize to the crystalline state and the bioavailability was decreased subsequently 5–5000 nm
Sonoprecipitation Simple setup; significant reduction in the use of organic solvents More suitable for production of amorphous nanoparticles; immersion depth of horn tip must be established experimentally; slow production time 80–130 nm
High gravity controlled precipitation(HGCP) Can produce crystalline particles; suspensions can be recycled for prolonged mixing and reaction; it has been scaled-up for commercial manufacturing; no need to use a stabilizer Equipment is highly specialized and not widely available 200–500 nm
Evaporative precipitation techniques Cost effective; easy to operate; can be easily scaled for massive production May not be suitable for heat-labile compounds 4–2600 nm
Rapid expansion of supercritical solution (RESS) Uniform size distribution; less processing steps Low solubility of polar drugs in sc-CO2; agglomeration of the small particles 45–500 nm
Supercritical anti-solvent (SAS) This process can take place at near ambient temperatures; small particle size; easy scale-up The presence of residual toxic solvents in the final product 45–500 nm
Spray freezing into liquid (SFL) Highly porous amorphous and smaller size nanocrystals in the form of solid solution are produced; improve dissolution rates and bioavailability of poorly water soluble APIs The drug should have a low glass transition temperature (Tg) ~7000 nm
Tab.2  Characteristics of bottom-up technologies [10,18,30,40-42]
Techniques Advantages Disadvantages Size ranges
Nanoedge? Improved particle size reduction effectiveness Residues of organic solvents in the nanosuspension, especially in large-scale production; the particle sizes are much bigger than the standard technologies; the process is often complicated and expensive 177-930 nm
H69 The top-down step reduces the particle size as well as stabilizes the nanocrystals with the applied energy; the annealing step promotes the more stable crystalline form The resulting nanosuspensions contain organic solvent residues. 22-921 nm
H42 Relatively short processing times during SD; solvent-free dry intermediates; small drug nanocrystals after a reduced number of HPH cycles The high temperatures applied during the SD could make this technology unsuitable to process thermolabile compounds 172-636 nm
H96 The low temperatures and the high yields of the FD make it suitable to process thermolabile or expensive drugs; the FD step eliminates the organic solvent content and make the nanosuspensions ready to be processed or used The extension of the FD step 62-440 nm
CT (Combinative Technology) The reduction of the homogenization pressure and process length; the improved physical stability of the nanosuspensions The particle sizes are relatively bigger than the other combinative processes 275-604 nm
Tab.3  Characteristics of combinative technologies [18]
Stabilizing system (%w/w to compound) Compound (%w/v in suspension ) Production method Category
Cremophor? EL (100%) 1,3-Dicyclohexyl urea (1%) MM Surfactant
Tyloxapol (50%) Budenoside (1%) HPH Surfactant
Lecithin (20%/40%/167%) RMKP 22 (3%) HPH Surfactant
Sodium lauryl sulfate (5%) Spironolactone (10%) HPH Surfactant
Poloxamer 338 (50%) Camtothecin (2%) MM Surfactant
Acacia gum (2%) ucb-35440-3 (5%) HPH Polymers
Polyvinyl alcohol (30-70 kDa; 50%) Beclomethasonedipropionate (5%) MM Polymers
HPC (60 kDa; 2.4%/4.8%/9.6%/19.3%) Undisclosed (16%) MM Polymers
Povidone K15 (30%) Danazol (5%) MM Polymers
Lecithin (50%)-tyloxapol (20%) Budenoside (1%) HPH Surfactant combination
Poloxamer 188 (100%)-lecithin (50%) Buparvaquone (1%) HPH Surfactant combination
Poloxamer 18-sodium deoxycholic acid Itraconazole HPH Surfactant combination
Tween? 80 (20%)-lecithin (10%) Azithromycin (1%) HPH Surfactant combination
Tween? 80 (16.7%)-Span 80 (33.3%) Piposulfan (2%) MM Surfactant combination
Carbopol 974 P (2.5%)-Tween? 80 (12.5%) Albendazole (4%) HPH Polymer-surfactant combination
HPC-sodium lauryl sulfate Cilostazol MM Polymer-surfactant combination
HPC (80%)-sodium lauryl sulfate (1.6%) MK-0869 (5%) MM Polymer-surfactant combination
HPMC (K4MCR; 12.5%)-Tween? 80 (12.5%) Albendazole (4%) HPH Polymer-surfactant combination
Polyvinyl alcohol (50%)-poloxamer 188 (50%) Buparvaquone (1%) HPH Polymer-surfactant combination
Tab.4  Selected stabilizing system for nanosuspension
Fig.3  (A) Comparison of micro-sized and nano-sized drug crystal in size and distribution in droplets [68]; (B) Advantageous absorption behavior of drug nanocrystals beyond micronized drug [69]
Fig.4  EPR effect. (A) Normal vessel: the narrow gap junctions present in between endothelial cells allow only small molecules to penetrate, screening out colloidal sized particles. Notice the ordered structure of cells in the presence of functional lymphatic drainage. Lymph flow regularly filters out accumulated material. (B) Tumor microenvironment: The vascular endothelium in and around the tumor is disjointed, irregular, and leaky, allowing effective penetration of nanocrystals. Absent or dysfunctional lymphatic vessels further delay clearance of these particles leading to their enhanced accumulation at tumor site [84]
1 Lipinski C. Poor aqueous solubility-an industry wide problem in drug discovery. American Pharmaceutical Review, 2002, 5: 82–85
2 Peters K, Muller R H. Nanosuspensions for the formulation of poorly soluble drugs I. Preparation by a size reduction technique. International Journal of Pharmaceutics, 1998, 160(2): 229–237
3 Fromming K H S, Fromming J. Cyclodextrines in Pharmacy. Dordrecht: Kluwer Academic, 1993
4 Muller R H. Dispersions for the formulation of slightly or poorly soluble drugs. US Patent, 7060285, 2001
5 Muller B W, Rasenack N. Micro-size drug particles: Common and novel micronization techniques. Pharmaceutical Development and Technology, 2003, 9: 1–13
6 Zhang D, Chen M, Gao L. Drug nanocrystals for the formulation of poorly solubledrugs and its application as a potential drug delivery system. Journal of Nanoparticle Research, 2008, 10(5): 845–862
7 Park J Y, Zhang Y, Liu F. Targeted cancer therapy with novel high drug-loading nanocrystals. Journal of Pharmaceutical Sciences, 2010, 99(8): 3542–3551
8 Luna I P, Sutradhar K B, Khatun S. Increasing possibilities of nanosuspension. Journal of Nanotechnology, 2013, 346581: 1–12
9 Abhijit A D, Kulkarni R M, Patravale V B. Nanosuspensions: A promising drug delivery strategy. Journal of Pharmacy and Pharmacology, 2004, 56(7): 827–840
10 Moschwitzer J P, Muller R H, Sinha B. Bottom-up approaches for preparing drug nanocrystals: Formulations and factors affecting particle size. International Journal of Pharmaceutics, 2013, 453(1): 126–141
11 Merisko-Liversidge E, Liversidge G G, Cooper E R. Nanosizing: a formulation approach for poorly-water-soluble compounds. European Journal of Pharmaceutical Sciences, 2003, 18(2): 113–120
12 Parmentier J, Widzinski M, Tan E H, Gokkhale R, Chin W W L. A brief literature and patent review of nanosuspensions to a final drug product. Journal of Pharmaceutical Sciences, 2014, 103(10): 2980–2999
13 M?schwitzer J P. Drug nanocrystals in the commercial pharmaceutical development process. International Journal of Pharmaceutics, 2013, 453(1): 142–156
14 Cundy G G, Bishop K C, Czekai J F, Liversidge D A. Surface modified drug nanoparticles. US Patent, 5145684, 1992
15 Muller R H, Shegokar R. Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives. International Journal of Pharmaceutics, 2010, 399(1-2): 129–139
16 Liversidge E M, Merisko-Liversidge G G. Drug nanoparticles: Formulating poorly water-soluble compounds. Toxicologic Pathology, 2008, 36(1): 43–48
17 Muller R H, Keck C M. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. European Journal of Pharmaceutics and Biopharmaceutics, 2006, 62(1): 3–16
https://doi.org/10.1016/j.ejpb.2005.05.009
18 Muller R H, Moschwitzer J P, Salazar J. Combinative particle size reduction technologies for the production of drug nanocrystals. Journal of Pharmaceutics, 2014, 265754: 1–14
19 Rabinow B E. Nanosupensions in drug delivery. Nature Reviews. Drug Discovery, 2004, 3(9): 785–796
20 Gohla S, Keck C M, Muller R H. State of the art of nanocrystals—Special features, production, nanotoxicology aspects and intracellular delivery. European Journal of Pharmaceutics and Biopharmaceutics, 2011, 78(1): 1–9
21 Haynes D H. Phospholipid-coated microcrystals: Injectable formulations of water insoluble drugs. US Patent, 5091187, 1992
22 Williams H D, Trevaskis N L, Charman S A, Shanker R M, Charman W N, Pouton C W, Porter C J H. Strategies to address low drug solubility in discovery and development. Pharmacological Reviews, 2013, 65(1): 315–499
23 Liversidge G G, Merisko-Liversidge E. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Advanced Drug Delivery Reviews, 2011, 63(6): 427–440
24 Muller R H, Junghanns J U A H. Nanocrystal technology, drug delivery and clinical applications. International Journal of Nanomedicine, 2008, 3(3): 295–309
25 Sucker H, Gassmann P. Improvements in pharmaceutical compositions. European Patent, 0580690, 1992
26 List M, Sucker H. Pharmaceutical colloidal hydrosols for injection. GB Patent, 2200048, 1988
27 Sharma S, Aggarwal G. Novel technologies for oral delivery of poorly soluble drugs. Research Journal of Pharmaceutical. Biological and Chemical Sciences, 2010, 1(4): 292–305
28 Bohn H, Auweter H, Heger R, Precipitated water-insoluble colorants in colloid disperse form. US Patent, 6494924, 2002
29 Auweter H, Andr’e V, Horn D, Luddecke E. The function of gelatin in controlled precipitation processes of nanosize particles. Journal of Dispersion Science and Technology, 1998, 19(2-7): 163–184
30 Chan H K, Kwok P C. Production methods for nanodrug particles using the bottom-up approach. Advanced Drug Delivery Rivew, 2011, 63(6): 406–416
31 Pacharane S, Chaudhry A, Jadhav K, Kadam V, Koshy P. Drug particle engineering of poorly water soluble drugs. Der Pharmacia Lettre, 2010, 2(4): 65–76
32 Kaerger J S, Price R. kaerger J S, Price R. Processing of spherical crystalline particles via a novel solution atomization and crystallization by sonication (SAXS) technique. Pharmaceutical Research, 2004, 21(2): 372–381
33 Wang Y H, Guo F, Wang X M, Zheng C, Chen J F. Synthesis of nanoparticles with novel technology: High-gravity reactive precipitation. Industrial & Engineering Chemistry Research, 2000, 39(4): 948–954
34 Zhang J Y, Shen Z G, Zhong J, Yun J, Chen J F. Preparation and characterization of amorphous cefuroxime axetil drug nanoparticles with novel technology: High-gravity antisolvent precipitation. Industrial & Engineering Chemistry Research, 2006, 45(25): 8723–8727
35 Brown J, Chen X, Swinnea S, Williams R O III, Johnston K P, Sarkari M. Enhanced drug dissolution using evaporative precipitation into aqueous solution. International Journal of Pharmaceutics, 2002, 243(1-2): 17–31
36 Sahoo N G, Li L, Judeh Z, Wang Y, Chong K, Loh L, Kakran M. Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. International Journal of Pharmaceutics, 2010, 383(1-2): 285–292
37 Singh S K, Nagpal K, Girotra P. Supercritical fluid technology: A promising approach in pharmaceutical research. Pharmaceutical Development and Technology, 2013, 18(1): 22–38
38 Montes A, Gordillo M D, Pereyra C, Martinez de la Ossa E J. Particles formation using supercritical fluids. In: Hironori Nakajima, ed. Mass Transfer-Advanced Aspects, 2011, 461–480
39 Turk M. Manufacture of submicron drug particles with enhanced dissolution behaviour by rapid expansion processes. Journal of Supercritical Fluids, 2009, 47(3): 537–545
40 Martín á, Mattea F, Varona S, Cocero M J. Encapsulation and co-precipitation processes with supercritical fluids: Fundamentals and applications. Journal of Supercritical Fluids, 2009, 47(3): 546–555
41 Kalani M, Yunus R. Application of supercritical antisolvent method in drug encapsulation: A review. International Journal of Nanomedicine, 2011, 6: 1429–1442
42 Rogers T L, Brown J, Young T, Johnston K P, Williams R O III, Hu J. Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid tecnology. Pharmaceutical Research, 2002, 19(9): 1278–1284
43 Moschwitzer J, Muller R H. New method for the effective production of ultrafine drug nanocrystals. Journal of Nanoscience and Nanotechnology, 2006, 6(9-10): 3145–3153
44 Wong J C T, Doty M J, Rebbeck C L, Kipp J E. Microprecipitation method for preparing submicron suspensions. US Patent, 6869617, 2001
45 Muller R H, Moschwitzer J. Method and device for producing very fine particles and coating such particles. US Patent, 0297565 A1, 2009
46 Gokhale R, Burgess D J, Verma S. A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. International Journal of Pharmaceutics, 2009, 380(1-2): 216–222
47 Keck C M, Kobierski S, Mauludin R, Muller R H. Second generation of drug nanocrystals for delivery of poorly soluble drugs: Smart crystal technology. Dosis, 2008, 24(2): 124–128
48 Mchwitzer R H, Bushrab J, Muller F N. Manufacturing of nanoparticles by milling and homogenization techniques. In: Gupta R B, Kompella U B, eds. Nanoparticle Technology for Drug Delivery. New York: CRC Press, 2006, 59: 21–51
49 Reddy I K, Nutan M T H. General Principles of Suspensions. In: Kulshreshtha A K, Singh O N, Wall G M, eds. Pharmaceutical Suspensions. New York: Springer-Verlag, 2009, 39–65
50 Heinzerling O, Salazar J, Muller R H, Moschwitzer J P. Process of optimization of a novel production method for nanosuspensions using design of experiments. International Journal of Pharmaceutics, 2011, 420(2): 395–403
51 Zhang J, Watanabe W, Wu L. Physical and chemical stability of drug nanoparticles. Advanced Drug Delivery Reviews, 2011, 63(6): 456–469
52 Landau B V, Derjaguin L. Theory of the stability of strongly charged lyophobic sols and of the adhesion of strongly charged particles in solutions of electrolytes. Acta Physico-Chimica Sinica, 1941, 14: 633–662
53 Van den Mooter G, Augustijns P, Van Eerdenbrugh B. Top-down production of drug nanocrystals: Nanosuspension stabilization, miniaturization and transformation into solid products. International Journal of Pharmaceutics, 2008, 364(1): 64–75
54 Wang Z H, Li T L, Lu Y. Development and evaluation of transferrin-stabilized paclitaxel nanocrystal formulation. Journal of Controlled Release, 2014, 176: 76–85
55 Liu R. Water-Insoluble Drug Formation. Buffalo Grove: Inter-Pharm Press, 2000, 455
56 Tian W, Zhang Y, Sun W, He J, Mao S, Fang L. Effect of novel stabilizers-cationic polymers on the particle size and physical stability of poorly soluble drug nanocrystals. Nanomedicine; Nanotechnology, Biology, and Medicine, 2012, 8(4): 460–467
57 Yoo J Y, Kwak H S, Choi J Y. Role of polymeric stabilizers for drug nanocrystal dispersions. Current Applied Physics, 2005, 5(5): 472–474
58 Peltonen L, Hirvonen J. Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods. Journal of Pharmacy and Pharmacology, 2010, 62(11): 1569–1579
59 Chase A R, Gibson G D, Granberg M R, Harvey C B, King S C, Martin R E, Medwick A N, Swinyard T, Zink E A, Gennaro G L. Colloidal dispersions. In: Alfonso R G, ed. Remington’s Pharmaceutical Sciences. Philadelphia: Mack Publishing Co., 1985, 286–289
60 Hartenhauer N, Muller R H, Rasenack B W. Microcrystals for dissolution rate enhancement of poorly water-soluble drugs. International Journal of Pharmaceutics, 2003, 254(2): 137–145
61 Muller N, Rasenack B W. Dissolution rate enhancement by in-situ-micronization of poorly water-soluble drugs using a controlled crystallization process. Pharmaceutical Research, 2002, 19: 1896–1902
62 Chandrasekhar V S R, Katteboinaa S. Drug nanocrystals: a novel formulation approach for poorly soluble drugs. International Journal of Pharm Tech Research, 2009, 1(3): 682–694
63 Whitney W R, Noyes A A. The rate of solution of solid substances in their own solutions. Journal of the American Chemical Society, 1897, 19(12): 930–934
64 Mehta S C, Higuchi W I, Simonelli A P. Inhibition of sulfathiazole crystal growth by polyvinylpyrrolidone. Journal of Pharmaceutical Sciences, 1970, 59: 633–638
65 Ponchel G, Duchene D. Bioadhesion of solid oral dosageforms, why and how? European Journal of Pharmaceutics and Biopharmaceutics, 1997, 44(1): 15–23
66 Lamprecht A, Ubrich N, Yamamoto H, Schafer U, Takeuchi H, Maincent P, Kawashima Y, Lehr C M. Biodegradable nanoparticles for targeted drug delivery intreatment ofinflammatory bowel disease. Journal of Pharmacology and Experimental Therapeutics, 2001, 299(2): 775–781
67 Jaitley V, Florence A T, Hussain N. Recent advancesin the understanding of uptake of microparticulates acrossthe gastrointestinallymphatic. Advanced Drug Delivery Reviews, 2001, 50(12): 107–142
68 Muller R H, Jacobs C. Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharmaceutical Research, 2002, 19(2): 189–194
69 Gangwal R P, Sangamwar A T, Jain S, Thanki K. Oral delivery of anticancer drugs: Challenges and opportunities. Journal of Controlled Release, 2013, 170(1): 15–40
70 Jacobs C, Kayser O, Muller R H. Production and characterisation of muco adhesive nanosuspensions for the formulation of bupravaquone. International Journal of Pharmaceutics, 2001, 214(1-2): 3–7
71 Conzentino G G, Liversidge P. Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats. International Journal of Pharmaceutics, 1995, 125(2): 309–313
72 Engers W M, Mueller D A, Eickhoff K R. Nanoparticulate NSAID Compositions, Application. US Patent, 5518738 A, 1996
73 Kayser O, Olbrich C, Yardley V, Kiderlen A F, Croft S L. Formulation of amphotericin B as nanosuspension for oral administration. International Journal of Pharmaceutics, 2003, 254(1): 73–75
74 Tu Z, Ng C, Yang Y, Liang J F, Agresti C. Specific interactions between diphenhydramine and alpha-helical poly(glutamic acid)-a new ion-pairing complex for taste masking and pH-controlled diphenhydramine release. European Journal of Pharmaceutics and Biopharmaceutics, 2008, 70(1): 226–233
75 Garg A, Aggarwal D, Singla A K. Paclitaxel and its formulations. International Journal of Pharmaceutics, 2002, 235(1-2): 179–192
76 Peters K, Leitjke S, Diederichs J E, Borner K, Hahn H, Muller R H, Ehlers S. Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. Journal of Antimicrobial Chemotherapy, 2000, 45(1): 77–83
77 Kayser O, Steckel H, Muller R H, Hernandez-Trejo N. Characterization of nebulised buparvaquone nanosuspension—effect of nebulization technology. Journal of Drug Targeting, 2005, 13(8-9): 499–507
78 Kayser O, Muller R H, Steckel H, Hernandez-Trejo N. Physical stability of buparvaquone nanosuspensions following nebulization with jet and ultrasonic nebulizers. In: Proceedings of the International Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Nuremberg Germany, 2004
79 Montisci M J, Dembri A, Ponchel G, Durrer C, Duchene D. Mucoadhesion of colloidal particulate systems in the gasrointesinal tract. European Journal of Pharmaceutics and Biopharmaceutics, 1997, 4: 25–31
80 Aggarwal P, Hall J B, McLeland C B, Dobrovolskaia M A, McNeil S E. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Advanced Drug Delivery Reviews, 2009, 61(6): 428–437
81 Liu Y, Huang L, Liu F. Paclitaxel nanocrystals for overcoming multidrug resistance in cancer. Molecular Pharmaceutics, 2010, 7(3): 863–869
82 Kayser O. Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against Leishmania infected macrophages. International Journal of Pharmaceutics, 2000, 196(2): 253–256
83 Mansell P. Nanocrystals could be route to carrier-free drug delivery. in-Pharma, 2007
84 Singh Y, Meher J G, Pawar V K, Gupta S, Chourasia M K. Engineered nanocrystal technology: In-vivo fate, targeting and applications in drug delivery. Journal of Controlled Release, 2014, 183: 51–66
85 Bansal M, Kumria R, Bansal S. Nanocrystals: Current strategies and trends. International Journal of Research in Pharmaceutical and Biomedical Sciences, 2012, 3(1): 406–419
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