Optimization of nanostructured lipid carriers: understanding the types, designs, and parameters in the process of formulations
Source abstract
Abstract
Lipid-based nanoparticles for drug delivery have been employed in the development of nanomedicine for various applications. One such versatile nanoparticle type is nanostructured lipid carriers (NLCs) that include multiple combinations of lipids and drugs for diverse routes of administrations. Optimization of NLCs to achieve ideal particle size distribution, dispersion in the aqueous environment, long-term stability, drug protection ability, and targeting features is necessary for designing improved drug formulations. However, very few studies have attempted to discuss explicitly the sequential requirements for optimization. Besides, several compositional variables can confound the design of an NLC drug formulation, making it essential for critical evaluation of factors that affect the NLC’s physicochemical properties. Therefore, this review intends to discuss the multi-step process taken during optimization and highlight the components, methods, statistical designs, trends observed between the variables, and modifications of NLCs for targeted delivery, with the objectives of improving efficiency and increasing success rates in drug delivery studies.
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Research context
OpenAlex topics: Advancements in Transdermal Drug Delivery · Drug Solubulity and Delivery Systems · Advanced Drug Delivery Systems
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Abouelmagd SA, Sun B, Chang AC, Ku YJ, Yeo Y (2015) Release kinetics study of poorly water-soluble drugs from nanoparticles: are we doing it right? Mol Pharm 12:997–100310.1021/mp500817h ↗
2. Aguilar, Zoraida. 2012. Nanomaterials for medical applications (Newnes)
3. Al-Qushawi A, Rassouli A, Atyabi F, Peighambari SM, Esfandyari-Manesh M, Shams GR, Yazdani A (2016) Preparation and characterization of three tilmicosin-loaded lipid nanoparticles: physicochemical properties and in-vitro antibacterial activities. Iran J Pharm Res 15:663–676
4. Alam T, Khan S, Gaba B, Haider MF, Baboota S, Ali J (2018) Adaptation of quality by design-based development of isradipine nanostructured–lipid carrier and its evaluation for in vitro gut permeation and in vivo solubilization fate. J Pharm Sci 107:2914–292610.1016/j.xphs.2018.07.021 ↗
5. Americas ICI (1984) The HLB system: a time-saving guide to emulsifier selection. ICI Americas, Incorporated
6. Andalib S, Varshosaz J, Hassanzadeh F, Sadeghi H (2012) Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design. Adv Biomed Res 1:4510.4103/2277-9175.100147 ↗
7. Araujo J, Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB (2010) Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications. Int J Pharm 393:167–17510.1016/j.ijpharm.2010.03.034 ↗
8. Arifin DY, Lee LY, Wang CH (2006) Mathematical modeling and simulation of drug release from microspheres: implications to drug delivery systems. Adv Drug Deliv Rev 58:1274–132510.1016/j.addr.2006.09.007 ↗
9. Asumadu-Mensah A, Smith KW, Ribeiro HS (2013) Solid lipid dispersions: potential delivery system for functional ingredients in foods. J Food Sci 78:E1000–E1E0810.1111/1750-3841.12162 ↗
10. Attama, Anthony A, Mumuni A Momoh, and Philip F Builders. 2012. Lipid nanoparticulate drug delivery systems: a revolution in dosage form design and development. in, Recent advances in novel drug carrier systems (Intech)
11. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–20510.1016/j.jconrel.2011.06.001 ↗
12. Bar-Zeev M, Livney YD, Assaraf YG (2017) Targeted nanomedicine for cancer therapeutics: towards precision medicine overcoming drug resistance. Drug Resist Updat 31:15–3010.1016/j.drup.2017.05.002 ↗
13. Béduneau A, Saulnier P, Hindré F, Clavreul A, Leroux J-C, Benoit J-P (2007) Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab’ fragments. Biomaterials 28:4978–499010.1016/j.biomaterials.2007.05.014 ↗
14. Beloqui A, Solinis MA, Delgado A, Evora C, del Pozo-Rodriguez A, Rodriguez-Gascon A (2013) Biodistribution of nanostructured lipid carriers (NLCs) after intravenous administration to rats: influence of technological factors. Eur J Pharm Biopharm 84:309–31410.1016/j.ejpb.2013.01.029 ↗
15. Beloqui A, Solinis MA, Delgado A, Evora C, Isla A, Rodriguez-Gascon A (2014) Fate of nanostructured lipid carriers (NLCs) following the oral route: design, pharmacokinetics and biodistribution. J Microencapsul 31:1–810.3109/02652048.2013.788090 ↗
16. Beloqui A, Solinis MA, Rodriguez-Gascon A, Almeida AJ, Preat V (2016) Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomedicine 12:143–16110.1016/j.nano.2015.09.004 ↗
17. Betts JN, Johnson MG, Rygiewicz PT, King GA, Andersen CP (2013) Potential for metal contamination by direct sonication of nanoparticle suspensions. Environ Toxicol Chem 32:889–89310.1002/etc.2123 ↗
18. Bhadra A, Karmakar G, Nahak P, Chettri P, Roy B, Guha P, Mandal AK, Nath RK, Panda AK (2017) Impact of detergents on the physiochemical behavior of itraconazole loaded nanostructured lipid carriers. Colloids Surf A Physicochem Eng Asp 516:63–7110.1016/j.colsurfa.2016.12.009 ↗
19. Bhadra D, Bhadra S, Jain P, Jain NK (2002) Pegnology: a review of PEG-ylated systems. Pharmazie 57:5–29
20. Bnyan R, Khan I, Ehtezazi T, Saleem I, Gordon S, O’Neill F, Roberts M (2018) Surfactant effects on lipid-based vesicles properties. J Pharm Sci 107:1237–124610.1016/j.xphs.2018.01.005 ↗
21. Bouchemal K, Briançon S, Perrier E, Fessi H (2004) Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation. Int J Pharm 280:241–25110.1016/j.ijpharm.2004.05.016 ↗
22. Box GEP, Behnken DW (1960) Some new three level designs for the study of quantitative variables. Technometrics 2:455–47510.1080/00401706.1960.10489912 ↗
23. Box, George EP, and Kenneth B Wilson. 1992. 'On the experimental attainment of optimum conditions.' in, Breakthroughs in statistics (Springer)10.1007/978-1-4612-4380-9_23 ↗
24. Bummer, Paul M. 2004. 'Physical chemical considerations of lipid-based oral drug delivery—solid lipid nanoparticles', Critical Reviews™ in Therapeutic Drug Carrier Systems, 2110.1615/CritRevTherDrugCarrierSyst.v21.i1.10 ↗
25. Campbell RB, Fukumura D, Brown EB, Mazzola LM, Izumi Y, Jain RK, Torchilin VP, Munn LL (2002) Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res 62:6831–6836
26. Casettari L, Illum L (2014) Chitosan in nasal delivery systems for therapeutic drugs. J Control Release 190:189–20010.1016/j.jconrel.2014.05.003 ↗
27. Chaudhary S, Garg T, Murthy RS, Rath G, Goyal AK (2015) Development, optimization and evaluation of long chain nanolipid carrier for hepatic delivery of silymarin through lymphatic transport pathway. Int J Pharm 485:108–12110.1016/j.ijpharm.2015.02.070 ↗
28. Chirio D, Gallarate M, Peira E, Battaglia L, Muntoni E, Riganti C, Biasibetti E, Capucchio MT, Valazza A, Panciani P (2014) Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment. Eur J Pharm Biopharm 88:746–75810.1016/j.ejpb.2014.10.017 ↗
29. Christensen JØ, Schultz K, Mollgaard B, Kristensen HG, Mullertz A (2004) Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium-and long-chain triacylglycerols. Eur J Pharm Sci 23:287–29610.1016/j.ejps.2004.08.003 ↗
30. D’Souza, Susan. 2014. 'A review of in vitro drug release test methods for nano-sized dosage forms', Advances in Pharmaceutics, 201410.1155/2014/304757 ↗
31. das Neves J, Sarmento B (2015) Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides. Acta Biomater 18:77–8710.1016/j.actbio.2015.02.007 ↗
32. Das S, Chaudhury A (2011) Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 12:62–7610.1208/s12249-010-9563-0 ↗
33. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223
34. Date AA, Vador N, Jagtap A, Nagarsenker MS (2011) Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery. Nanotechnology 22:27510210.1088/0957-4484/22/27/275102 ↗
35. Deckert PM (2009) Current constructs and targets in clinical development for antibody-based cancer therapy. Curr Drug Targets 10:158–17510.2174/138945009787354502 ↗
36. Draper NR, Hunter WG (1966) Design of experiments for parameter estimation in multiresponse situations. Biometrika 53:525–53310.1093/biomet/53.3-4.525 ↗
37. Dudhipala N, Janga KY, Gorre T (2018) Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artif Cells Nanomed Biotechnol 46:616–62510.1080/21691401.2018.1465068 ↗
38. Effendy I, Maibach HI (1995) Surfactants and experimental irritant contact dermatitis. Contact Dermatitis 33:217–22510.1111/j.1600-0536.1995.tb00470.x ↗
39. El Assasy AEI, Younes NF, Makhlouf AIA (2019) Enhanced oral absorption of amisulpride via a nanostructured lipid carrier-based capsules: development, optimization applying the desirability function approach and in vivo pharmacokinetic study. AAPS PharmSciTech 20:8210.1208/s12249-019-1321-3 ↗
40. Elmowafy M, Shalaby K, Badran MM, Ali HM, Abdel-Bakky MS, Ibrahim HM (2018) Multifunctional carbamazepine loaded nanostructured lipid carrier (NLC) formulation. Int J Pharm 550:359–37110.1016/j.ijpharm.2018.08.062 ↗
41. Emami J, Rezazadeh M, Varshosaz J, Tabbakhian M, Aslani A (2012) Formulation of LDL targeted nanostructured lipid carriers loaded with paclitaxel: a detailed study of preparation, freeze drying condition, and in vitro cytotoxicity. J Nanomater 2012:1–1010.1155/2012/358782 ↗
42. Fathi HA, Allam A, Elsabahy M, Fetih G, El-Badry M (2018) Nanostructured lipid carriers for improved oral delivery and prolonged antihyperlipidemic effect of simvastatin. Colloids Surf B Biointerfaces 162:236–24510.1016/j.colsurfb.2017.11.064 ↗
43. Fatouh, Ahmed M, Ahmed H Elshafeey, and Ahmed Abdelbary (2017) Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics. Drug Design, development and therapy, 11: 1815, 182510.2147/DDDT.S102500 ↗
44. Ferreira M, Chaves LL, Lima SA, Reis S (2015) Optimization of nanostructured lipid carriers loaded with methotrexate: a tool for inflammatory and cancer therapy. Int J Pharm 492:65–7210.1016/j.ijpharm.2015.07.013 ↗
45. Fishman JB, Rubin JB, Handrahan JV, Connor JR, Fine RE (1987) Receptor-mediated transcytosis of transferrin across the blood-brain barrier. J Neurosci Res 18:299–30410.1002/jnr.490180206 ↗
46. Gao X, Zhang J, Xu Q, Huang Z, Wang Y, Shen Q (2017) Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery. Drug Dev Ind Pharm 43:661–66710.1080/03639045.2016.1275671 ↗
47. Garcia-Orue I, Gainza G, Girbau C, Alonso R, Aguirre JJ, Pedraz JL, Igartua M, Hernandez RM (2016) LL37 loaded nanostructured lipid carriers (NLC): a new strategy for the topical treatment of chronic wounds. Eur J Pharm Biopharm 108:310–31610.1016/j.ejpb.2016.04.006 ↗
48. Gartziandia O, Herran E, Ruiz-Ortega JA, Miguelez C, Igartua M, Lafuente JV, Pedraz JL, Ugedo L, Hernandez RM (2016) Intranasal administration of chitosan-coated nanostructured lipid carriers loaded with GDNF improves behavioral and histological recovery in a partial lesion model of Parkinson’s disease. J Biomed Nanotechnol 12:2220–223010.1166/jbn.2016.2313 ↗
49. Ghate VM, Lewis SA, Prabhu P, Dubey A, Patel N (2016) Nanostructured lipid carriers for the topical delivery of tretinoin. Eur J Pharm Biopharm 108:253–26110.1016/j.ejpb.2016.07.026 ↗
50. Ghorab MAMDOUH, Gardouh AHMAD, Gad SHADEED (2015) Effect of viscosity, surfactant type and concentration on physicochemical properties of solid lipid nanoparticles. Int J Pharm Pharm Sci 7:145–153
51. Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB (2010) Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids Surf B Biointerfaces 81:412–42110.1016/j.colsurfb.2010.07.029 ↗
52. Gordillo-Galeano A, Mora-Huertas CE (2018) Solid lipid nanoparticles and nanostructured lipid carriers: a review emphasizing on particle structure and drug release. Eur J Pharm Biopharm 133:285–30810.1016/j.ejpb.2018.10.017 ↗
53. Grislain L, Patrick C, Lenaerts V, Marie R, Deprez-Decampeneere D, Speiser P (1983) Pharmacokinetics and distribution of a biodegradable drug-carrier. Int J Pharm 15:335–34510.1016/0378-5173(83)90166-7 ↗
54. Gupta Y, Jain A, Jain SK (2007) Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain. J Pharm Pharmacol 59:935–94010.1211/jpp.59.7.0004 ↗
55. Han F, Li S, Yin R, Liu H, Lu X (2008) Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: nanostructured lipid carriers. Colloids Surf A Physicochem Eng Asp 315:210–21610.1016/j.colsurfa.2007.08.005 ↗
56. Han Y, Zhang Y, Li D, Chen Y, Sun J, Kong F (2014) Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin. Int J Nanomedicine 9:4107–4116
57. Harivardhan Reddy L, Vivek K, Bakshi N, Murthy RSR (2006) Tamoxifen citrate loaded solid lipid nanoparticles (SLN™): preparation, characterization, in vitro drug release, and pharmacokinetic evaluation. Pharm Dev Technol 11:167–17710.1080/10837450600561265 ↗
58. Hejri A, Khosravi A, Gharanjig K, Hejazi M (2013) Optimisation of the formulation of beta-carotene loaded nanostructured lipid carriers prepared by solvent diffusion method. Food Chem 141:117–12310.1016/j.foodchem.2013.02.080 ↗
59. Hibbert DB (2012) Experimental design in chromatography: a tutorial review. J Chromatogr B 910:2–1310.1016/j.jchromb.2012.01.020 ↗
60. Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S (2005) Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B Biointerfaces 45:167–17310.1016/j.colsurfb.2005.08.005 ↗
61. Huang R, Li J, Kebebe D, Wu Y, Zhang B, Liu Z (2018) Cell penetrating peptides functionalized gambogic acid-nanostructured lipid carrier for cancer treatment. Drug Deliv 25:757–76510.1080/10717544.2018.1446474 ↗
62. Jawahar N, Hingarh PK, Arun R, Selvaraj J, Arigo A, Sathianarayanan S, Nagaraju G (2018) Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers. Int J Biol Macromol 110:269–27510.1016/j.ijbiomac.2018.01.121 ↗
63. Joshi M, Patravale V (2008) Nanostructured lipid carrier (NLC) based gel of celecoxib. Int J Pharm 346:124–13210.1016/j.ijpharm.2007.05.060 ↗
64. Joshi M, Pathak S, Sharma S, Patravale V (2008) Design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: Nanoject. Int J Pharm 364:119–12610.1016/j.ijpharm.2008.07.032 ↗
65. Karn-Orachai K, Smith SM, Phunpee S, Treethong A, Puttipipatkhachorn S, Pratontep S, Ruktanonchai UR (2014) The effect of surfactant composition on the chemical and structural properties of nanostructured lipid carriers. J Microencapsul 31:609–61810.3109/02652048.2014.911374 ↗
66. Kasongo WA, Pardeike J, Müller RH, Walker RB (2011) Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers. J Pharm Sci 100:5185–519610.1002/jps.22711 ↗
67. Kaukonen, Ann Marie, Ben J Boyd, Christopher JH Porter, and William N Charman. 2004. 'Drug solubilization behavior during in vitro digestion of simple triglyceride lipid solution formulations', Pharm Res, 21: 245–25310.1023/B:PHAM.0000016282.77887.1f ↗
68. Kaur P, Garg T, Goutam R, Rayasa Murthy RS, Goyal AK (2016) Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken design. Drug delivery 23:1912–1925
69. Kaur S, Nautyal U, Singh R, Singh S, Devi A (2015) Nanostructure lipid carrier (NLC): the new generation of lipid nanoparticles. Asian Pac J Health Sci 2:76–9310.21276/apjhs.2015.2.2.14 ↗
70. Kelidari HR, Moazeni M, Babaei R, Saeedi M, Akbari J, Parkoohi PI, Nabili M, Gohar AA, Morteza-Semnani K, Nokhodchi A (2017a) Improved yeast delivery of fluconazole with a nanostructured lipid carrier system. Biomed Pharmacother 89:83–8810.1016/j.biopha.2017.02.008 ↗
71. Kelidari HR, Saeedi M, Akbari J, Morteza-Semnani K, Valizadeh H, Maniruzzaman M, Farmoudeh A, Nokhodchi A (2017b) Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability. AAPS PharmSciTech 18:1469–147410.1208/s12249-016-0621-0 ↗
72. Keshri L, Pathak K (2013) Development of thermodynamically stable nanostructured lipid carrier system using central composite design for zero order permeation of econazole nitrate through epidermis. Pharm Dev Technol 18:634–64410.3109/10837450.2012.659256 ↗
73. Khan S, Shaharyar M, Fazil M, Baboota S, Ali J (2016) Tacrolimus-loaded nanostructured lipid carriers for oral delivery - optimization of production and characterization. Eur J Pharm Biopharm 108:277–28810.1016/j.ejpb.2016.07.017 ↗
74. Khan S, Baboota S, Ali J, Khan S, Narang RS, Narang JK (2015) Nanostructured lipid carriers: an emerging platform for improving oral bioavailability of lipophilic drugs. International journal of pharmaceutical investigation 5:18210.4103/2230-973X.167661 ↗
75. Khuri AI, Mukhopadhyay S (2010) Response surface methodology. Wiley Interdisciplinary Reviews: Computational Statistics 2:128–14910.1002/wics.73 ↗
76. Kraisit P, Sarisuta N (2018) Development of triamcinolone acetonide-loaded nanostructured lipid carriers (NLCs) for buccal drug delivery using the Box-Behnken design. Molecules 23:98210.3390/molecules23040982 ↗
77. Kudarha R, Dhas NL, Pandey A, Belgamwar VS, Ige PP (2015) Box-Behnken study design for optimization of bicalutamide-loaded nanostructured lipid carrier: stability assessment. Pharm Dev Technol 20:608–61810.3109/10837450.2014.908305 ↗
78. Kumar R, Yasir M, Saraf SA, Gaur PK, Kumar Y, Singh AP (2013) Glyceryl monostearate based nanoparticles of mefenamic acid: fabrication and in vitro characterization. Drug Invention Today 5:246–25010.1016/j.dit.2013.06.011 ↗
79. Kumbhar DD, Pokharkar VB (2013) Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: physicochemical investigations. Colloids Surf A Physicochem Eng Asp 416:32–4210.1016/j.colsurfa.2012.10.031 ↗
80. Lasoń E, Sikora E, Miastkowska M, Escribano E, Garcia-Celma MJ, Solans C, Llinas M, Ogonowski J (2018) NLC as a potential carrier system for transdermal delivery of forskolin. Polonica, Acta Biochimica
81. Lasoń, Elwira, Elżbieta Sikora, and Jan Ogonowski. 2013. 'Influence of process parameters on properties of nanostructured lipid carriers (NLC) formulation', Acta Biochimica Polonica, 6010.18388/abp.2013_2056 ↗
82. Lémery E, Briançon S, Chevalier Y, Bordes C, Oddos T, Gohier A, Bolzinger M-A (2015) Skin toxicity of surfactants: structure/toxicity relationships. Colloids Surf A Physicochem Eng Asp 469:166–17910.1016/j.colsurfa.2015.01.019 ↗
83. Lewis MA (1990) Chronic toxicities of surfactants and detergent builders to algae: a review and risk assessment. Ecotoxicol Environ Saf 20:123–14010.1016/0147-6513(90)90052-7 ↗
84. Li H, Wang K, Yang X, Zhou Y, Ping Q, Oupicky D, Sun M (2017) Dual-function nanostructured lipid carriers to deliver IR780 for breast cancer treatment: anti-metastatic and photothermal anti-tumor therapy. Acta Biomater 53:399–41310.1016/j.actbio.2017.01.070 ↗
85. Li S, Ji Z, Zou M, Nie X, Shi Y, Cheng G (2011) Preparation, characterization, pharmacokinetics and tissue distribution of solid lipid nanoparticles loaded with tetrandrine. AAPS PharmSciTech 12:1011–101810.1208/s12249-011-9665-3 ↗
86. Li Y, Wang J, Wientjes MG, Au JL (2012) Delivery of nanomedicines to extracellular and intracellular compartments of a solid tumor. Adv Drug Deliv Rev 64:29–3910.1016/j.addr.2011.04.006 ↗
87. Lin WJ, Duh YS (2016) Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole. Eur J Pharm Biopharm 108:297–30310.1016/j.ejpb.2016.07.015 ↗
88. Liu M, Chen D, Mukerabigwi JF, Chen S, Zhang Y, Lei S, Luo S, Wen Z, Cao Y, Huang X, He H (2016) Intracellular delivery of 10-hydroxycamptothecin with targeted nanostructured lipid carriers against multidrug resistance. J Drug Target 24:433–44010.3109/1061186X.2015.1086358 ↗
89. Liu W, Tian R, Hu W, Jia Y, Jiang H, Zhang J, Zhang L (2012) Preparation and evaluation of self-microemulsifying drug delivery system of baicalein. Fitoterapia 83:1532–153910.1016/j.fitote.2012.08.021 ↗
90. Liu Y, Wang L, Zhao Y, He M, Zhang X, Niu M, Feng N (2014) Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin. Int J Pharm 476:169–17710.1016/j.ijpharm.2014.09.052 ↗
91. Loo C, Basri M, Ismail R, Lau H, Tejo B, Kanthimathi M, Hassan H, Choo Y (2013) Effect of compositions in nanostructured lipid carriers (NLC) on skin hydration and occlusion. Int J Nanomedicine 8:13–2210.2217/nnm.12.191 ↗
92. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–28410.1016/S0168-3659(99)00248-5 ↗
93. Maruyama K, Ishida O, Kasaoka S, Takizawa T, Utoguchi N, Shinohara A, Chiba M, Kobayashi H, Eriguchi M, Yanagie H (2004) Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT). J Control Release 98:195–20710.1016/j.jconrel.2004.04.018 ↗
94. Mehnert W, Mader K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–19610.1016/S0169-409X(01)00105-3 ↗
95. Miao J, Zhang X-g, Hong Y, Rao Y-f, Li Q, Xie X-j, Wo J-e, Li M-w (2012) Inhibition on hepatitis B virus e-gene expression of 10–23 DNAzyme delivered by novel chitosan oligosaccharide–stearic acid micelles. Carbohydr Polym 87:1342–134710.1016/j.carbpol.2011.09.022 ↗
96. Mills JK, Needham D (1999) Targeted drug delivery. Expert Opinion on Therapeutic Patents 9:1499–151310.1517/13543776.9.11.1499 ↗
97. Mitri K, Shegokar R, Gohla S, Anselmi C, Muller RH (2011) Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm 414:267–27510.1016/j.ijpharm.2011.05.008 ↗
98. Monteiro LM, Lobenberg R, Cotrim PC, Barros de Araujo GL, Bou-Chacra N (2017) Buparvaquone nanostructured lipid carrier: development of an affordable delivery system for the treatment of leishmaniases. Biomed Res Int 2017:978160310.1155/2017/9781603 ↗
99. Montgomery, Douglas C. 2017. Design and analysis of experiments (John wiley & sons)
100. Muller RH, Shegokar R, Keck CM (2011) 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol 8:207–22710.2174/157016311796799062 ↗