A Detailed Insight into Nanostructured Lipid Carriers: A Versatile Drug
Delivery System

Samarjit      Ghosh; Triveni      Tiwari; Upendra      Nagaich; Neha      Jain
Abstract

The advent of technology provides a solution to various drug delivery-related problems by undertaking the development of a better drug delivery system, i.e., nano-sized drug delivery systems as they have shown huge prospects for effective delivery of drugs in the body. Nanostructured lipid carriers (NLCs) are such type of novel drug delivery system in which lipids of both solid and liquid types are used as a core for the disorganized matrix, which prevents the solid lipid crystallization and increases drug payload. They are generally composed of solid and liquid lipids, emulsifiers, drugs, and other various additives, which are selected based on purity, chemical stability, the concentration of materials required, compatibility, biodegradability, processing type, cost, and their regulatory status. Placing bioactives into nanostructured lipid carriers (NLCs) has enhanced pharmacokinetic characteristics by increasing therapeutic functionality and prolonging release from these carrier systems. In our opinion, the search involves two steps viz. fabrication strategies, production methods, and the impact of various types of substances on them, as well as the release mechanism and targeting modalities. In addition to other applications, the use of NLCs in gene therapy has marked a promising path for new and better drug delivery systems. Further development of various dosage forms using NLCs, like NLC based hydrogels, is being done for improving the overall aesthetic properties, leading to the desired therapeutic effect of the incorporated active. This review highlights several elements of NLCs, such as structural model and types, excipients utilized, factors affecting NLC production, preparation techniques, characterization, current applications, patents, challenges, and opportunities.
Keywords: Nanostructured lipid carriers, nanomedicine, nanotherapeutics, solid lipid, liquid lipid, surfactants.
Graphical Abstract

[1]
Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother  2018; 103: 598-613.
 [http://dx.doi.org/10.1016/j.biopha.2018.04.055] [PMID:  29677547]

[2]
Chao X, Zhao L, Ma N, Mou Y, Zhang P. Nanotechnology-based drug delivery systems for the improved sensitization of tamoxifen. J Drug Deliv Sci Technol  2021; 61: 102229.
 [http://dx.doi.org/10.1016/j.jddst.2020.102229]

[3]
Rahdar A, Hajinezhad MR, Barani M, et al. Pluronic F127/Doxorubicin microemulsions: Preparation, characterization, and toxicity evaluations. J Mol Liq  2022; 345: 117028.
 [http://dx.doi.org/10.1016/j.molliq.2021.117028]

[4]
Rahdar A, Hajinezhad MR, Nasri S, Beyzaei H, Barani M, Trant JF. The synthesis of methotrexate-loaded F127 microemulsions and their in vivo toxicity in a rat model. J Mol Liq  2020; 313: 113449.
 [http://dx.doi.org/10.1016/j.molliq.2020.113449]

[5]
Mishra V, Bansal KK, Verma A, et al. Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems. Pharmaceutics  2018; 10(4): E191.
 [http://dx.doi.org/10.3390/pharmaceutics10040191] [PMID:  30340327]

[6]
Amaldoss MJ. Newton, Sukhjinder Kaur Solid lipid nanoparticles for skin and drug delivery. In: Alexandru MG, Ed. Nanoarchitectonics in Biomedicine.  William Andrew 2019; pp. 295-334.
 [http://dx.doi.org/10.1016/B978-0-12-816200-2.00015-3]

[7]
Rizwanullah M, Ahmad J, Amin S. Nanostructured lipid carriers: A novel platform for chemotherapeutics. Curr Drug Deliv  2016; 13(1): 4-26.
 [http://dx.doi.org/10.2174/1567201812666150817124133] [PMID:  26279117]

[8]
Fang C-L, Al-Suwayeh SA, Fang J-Y. Nanostructured lipid carriers (nlcs) for drug delivery and targeting. Recent Pat Nanotechnol  2012; 7(1): 41-55.
 [http://dx.doi.org/10.2174/1872210511307010041]

[9]
How CW, Abdullah R, Abbasalipourkabir R. Physicochemical properties of nanostructured lipid carriers as colloidal carrier system stabilized with polysorbate 20 and polysorbate 80. Afr J Biotechnol  2011; •••: 10.

[10]
Li Q, Cai T, Huang Y, Xia X, Cole SPC, Cai Y. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials (Basel)  2017; 7(6): E122.
 [http://dx.doi.org/10.3390/nano7060122] [PMID:  28554993]

[11]
Vieira R, Severino P, Nalone LA, et al. Sucupira oil-loaded nanostructured lipid carriers (NLC): Lipid screening, factorial design, release profile, and cytotoxicity. Molecules  2020; 25(3): E685.
 [http://dx.doi.org/10.3390/molecules25030685] [PMID:  32041134]

[12]
Patel P, Patel M. Nanostructured lipid carriers- a versatile carrier for oral delivery of lipophilic drugs. Recent Pat Nanotechnol  2021; 15(2): 154-64.
 [http://dx.doi.org/10.2174/1872210514666200909154959] [PMID:  32912129]

[13]
Subramaniam B, Arshad NM, Malagobadan S, et al. Development and evaluation of 10-acetoxychavicol acetate (ACA)-loaded nanostructured lipid carriers for prostate cancer therapy. Pharmaceutics  2021; 13(4): 439.
 [http://dx.doi.org/10.3390/pharmaceutics13040439] [PMID:  33804975]

[14]
Jhaveri A, Deshpande P, Torchilin V. Stimuli-sensitive nanopreparations for combination cancer therapy. J Control Release  2014; 190: 352-70.
 [http://dx.doi.org/10.1016/j.jconrel.2014.05.002] [PMID:  24818767]

[15]
Obata Y, Tajima S, Takeoka S. Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo. J Control Release  2010; 142(2): 267-76.
 [http://dx.doi.org/10.1016/j.jconrel.2009.10.023] [PMID:  19861141]

[16]
Tannock IF, Rotin D. Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res  1989; 49(16): 4373-84.
 [PMID:  2545340]

[17]
Wang YC, Wang F, Sun TM, Wang J. Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjug Chem  2011; 22(10): 1939-45.
 [http://dx.doi.org/10.1021/bc200139n] [PMID:  21866903]

[18]
Torchilin V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm  2009; 71(3): 431-44.
 [http://dx.doi.org/10.1016/j.ejpb.2008.09.026] [PMID:  18977297]

[19]
Dicheva BM, Koning GA. Targeted thermosensitive liposomes: An attractive novel approach for increased drug delivery to solid tumors. Expert Opin Drug Deliv  2014; 11(1): 83-100.
 [http://dx.doi.org/10.1517/17425247.2014.866650] [PMID:  24320104]

[20]
Fomina N, McFearin C, Sermsakdi M, Edigin O, Almutairi A. UV and near-IR triggered release from polymeric nanoparticles. J Am Chem Soc  2010; 132(28): 9540-2.
 [http://dx.doi.org/10.1021/ja102595j] [PMID:  20568765]

[21]
Schroeder A, Honen R, Turjeman K, Gabizon A, Kost J, Barenholz Y. Ultrasound triggered release of cisplatin from liposomes in murine tumors. J Control Release  2009; 137(1): 63-8.
 [http://dx.doi.org/10.1016/j.jconrel.2009.03.007] [PMID:  19303426]

[22]
Martinelli C, Pucci C, Ciofani G. Nanostructured carriers as innovative tools for cancer diagnosis and therapy. APL Bioeng  2019; 3(1): 011502.
 [http://dx.doi.org/10.1063/1.5079943] [PMID:  31069332]

[23]
Hsu SH, Wen CJ, Al-Suwayeh SA, Huang YJ, Fang JY. Formulation design and evaluation of quantum dot-loaded nanostructured lipid carriers for integrating bioimaging and anticancer therapy. Nanomedicine (Lond)  2013; 8(8): 1253-69.
 [http://dx.doi.org/10.2217/nnm.12.170] [PMID:  23384703]

[24]
Zheng S, Nguyen VD, Song SY, Han J, Park JO. Combined photothermal-chemotherapy of breast cancer by near infrared light responsive hyaluronic acid-decorated nanostructured lipid carriers. Nanotechnology  2017; 28(43): 435102.
 [http://dx.doi.org/10.1088/1361-6528/aa847f] [PMID:  28783035]

[25]
Fernandes RS, Silva JO, Mussi SV, et al. Nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid as a theranostic agent: Evaluation of biodistribution and antitumor activity in experimental model. Mol Imaging Biol  2018; 20(3): 437-47.
 [http://dx.doi.org/10.1007/s11307-017-1133-3] [PMID:  29043471]

[26]
Chen J, Chen H, Cui S, et al. Glucosamine derivative modified nanostructured lipid carriers for targeted tumor delivery. J Mater Chem  2012; 22(12): 5770-83.
 [http://dx.doi.org/10.1039/c2jm15830b]

[27]
Selvamuthukumar S, Velmurugan R. Nanostructured lipid carriers: A potential drug carrier for cancer chemotherapy. Lipids Health Dis  2012; 11(1): 159.
 [http://dx.doi.org/10.1186/1476-511X-11-159] [PMID:  23167765]

[28]
Shah R, Eldridge D, Palombo E, Harding I. Lipid nanoparticles: Production, characterization and stability. 2015.

[29]
Chauhan I, Yasir M, Verma M, Singh AP. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Adv Pharm Bull  2020; 10(2): 150-65.
 [http://dx.doi.org/10.34172/apb.2020.021] [PMID:  32373485]

[30]
Kanwar R, Rathee J, Salunke DB, Mehta SK. Green nanotechnology-driven drug delivery assemblies. ACS Omega  2019; 4(5): 8804-15.
 [http://dx.doi.org/10.1021/acsomega.9b00304] [PMID:  31459969]

[31]
Aditya NP, Macedo AS, Doktorovova S, et al. Development and evaluation of lipid nanocarriers for quercetin delivery: A comparative study of solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid nanoemulsions (LNE). Lebensm Wiss Technol  2014; 59(1): 115-21.
 [http://dx.doi.org/10.1016/j.lwt.2014.04.058]

[32]
Martins S, Sarmento B, Ferreira DC, Souto EB. Lipid-based colloidal carriers for peptide and protein delivery--liposomes versus lipid nanoparticles. Int J Nanomedicine  2007; 2(4): 595-607.
 [PMID:  18203427]

[33]
Zhou J, Zhou D. Improvement of oral bioavailability of lovastatin by using nanostructured lipid carriers. Drug Des Devel Ther  2015; 9: 5269-75.
 [http://dx.doi.org/10.2147/DDDT.S90016] [PMID:  26425076]

[34]
Karn-Orachai K, Smith SM, Phunpee S, et al. The effect of surfactant composition on the chemical and structural properties of nanostructured lipid carriers. J Microencapsul  2014; 31(6): 609-18.
 [http://dx.doi.org/10.3109/02652048.2014.911374] [PMID:  24861323]

[35]
Han F, Li S, Yin R, Liu H, Xu L. 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  2008; 315(1-3): 210-6.
 [http://dx.doi.org/10.1016/j.colsurfa.2007.08.005]

[36]
Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: Structure preparation and application. Adv Pharm Bull  2015; 5(3): 305-13.
 [http://dx.doi.org/10.15171/apb.2015.043] [PMID:  26504751]

[37]
Yoon G, Park JW, Yoon IS. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): Recent advances in drug delivery. J Pharm Investig  2013; 43(5): 353-62.
 [http://dx.doi.org/10.1007/s40005-013-0087-y]

[38]
Beloqui A, del Pozo-Rodríguez A, Isla A, Rodríguez-Gascón A, Solinís MÁ. Nanostructured lipid carriers as oral delivery systems for poorly soluble drugs. J Drug Deliv Sci Technol  2017; 42: 144-54.
 [http://dx.doi.org/10.1016/j.jddst.2017.06.013]

[39]
Liu Y, Wang L, Zhao Y, et al. Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin. Int J Pharm  2014; 476(1-2): 169-77.
 [http://dx.doi.org/10.1016/j.ijpharm.2014.09.052] [PMID:  25280882]

[40]
Beloqui A, Solinís MÁ, Gascón AR, del Pozo-Rodríguez A, des Rieux A, Préat V. Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier. J Control Release  2013; 166(2): 115-23.
 [http://dx.doi.org/10.1016/j.jconrel.2012.12.021] [PMID:  23266764]

[41]
Sharma M, Sharma R, Jain DK, Saraf A. Enhancement of oral bioavailability of poorly water soluble carvedilol by chitosan nanoparticles: Optimization and pharmacokinetic study. Int J Biol Macromol  2019; 135: 246-60.
 [http://dx.doi.org/10.1016/j.ijbiomac.2019.05.162] [PMID:  31128197]

[42]
Pinheiro M, Ribeiro R, Vieira A, Andrade F, Reis S. Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis. Drug Des Devel Ther  2016; 10: 2467-75.
 [http://dx.doi.org/10.2147/DDDT.S104395] [PMID:  27536067]

[43]
Lacatusu I, Mitrea E, Badea N, Stan R, Oprea O, Meghea A. Lipid nanoparticles based on omega-3 fatty acids as effective carriers for lutein delivery. Preparation and in vitro characterization studies. J Funct Foods  2013; 5(3): 1260-9.
 [http://dx.doi.org/10.1016/j.jff.2013.04.010]

[44]
Guilherme VA, Ribeiro LNM, Tofoli GR, Franz-Montan M, de Paula E, de Jesus MB. Current challenges and future of lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye. Curr Pharm Des  2017; 23(43): 6659-75.
 [http://dx.doi.org/10.2174/1381612823666171122103849] [PMID:  29173149]

[45]
Karimi N, Ghanbarzadeh B, Hamishehkar H, Mehramuz B, Kafil HS. Antioxidant, Antimicrobial and Physicochemical Properties of Turmeric Extract-Loaded Nanostructured Lipid Carrier (NLC). Colloid Interface Sci Commun  2018; 22: 18-24.
 [http://dx.doi.org/10.1016/j.colcom.2017.11.006]

[46]
Lin C, Chen F, Ye T, et al. A novel oral delivery system consisting in “drug-in cyclodextrin-in nanostructured lipid carriers” for poorly water-soluble drug: Vinpocetine. Int J Pharm  2014; 465(1-2): 90-6.
 [http://dx.doi.org/10.1016/j.ijpharm.2014.02.013] [PMID:  24530388]

[47]
Mendes AI, Silva AC, Catita JAM, Cerqueira F, Gabriel C, Lopes CM. Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: Improving antifungal activity. Colloids Surf B Biointerfaces  2013; 111: 755-63.
 [http://dx.doi.org/10.1016/j.colsurfb.2013.05.041] [PMID:  23954816]

[48]
Tian Z, Yi Y, Yuan H, et al. Solidification of nanostructured lipid carriers (NLCs) onto pellets by fluid-bed coating: Preparation, in vitro characterization and bioavailability in dogs. Powder Technol  2013; 247: 120-7.
 [http://dx.doi.org/10.1016/j.powtec.2013.07.010]

[49]
Mandpe L, Pokharkar V. Quality by design approach to understand the process of optimization of iloperidone nanostructured lipid carriers for oral bioavailability enhancement. Pharm Dev Technol  2015; 20(3): 320-9.
 [http://dx.doi.org/10.3109/10837450.2013.867445] [PMID:  24328553]

[50]
Elnaggar YSR, El-Massik MA, Abdallah OY. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles. Int J Nanomedicine  2011; 6: 3195-205.
 [http://dx.doi.org/10.2147/IJN.S25825] [PMID:  22238508]

[51]
Elmowafy M, Al-Sanea MM. Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies. Saudi Pharm J  2021; 29(9): 999-1012.
 [http://dx.doi.org/10.1016/j.jsps.2021.07.015] [PMID:  34588846]

[52]
Patil-Gadhe A, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: Part I oral bioavailability improvement. Eur J Pharm Biopharm  2014; 88(1): 160-8.
 [http://dx.doi.org/10.1016/j.ejpb.2014.05.019] [PMID:  24878424]

[53]
Date AA, Vador N, Jagtap A, Nagarsenker MS. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: Fabrication, characterization and evaluation for oral drug delivery. Nanotechnology  2011; 22(27): 275102.
 [http://dx.doi.org/10.1088/0957-4484/22/27/275102] [PMID:  21606564]

[54]
Yuan H, Wang LL, Du YZ, You J, Hu FQ, Zeng S. Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification. Colloids Surf B Biointerfaces  2007; 60(2): 174-9.
 [http://dx.doi.org/10.1016/j.colsurfb.2007.06.011] [PMID:  17656075]

[55]
Salvi VR, Pawar P. Nanostructured lipid carriers (NLC) system: A novel drug targeting carrier. J Drug Deliv Sci Technol  2019; 51: 255-67.
 [http://dx.doi.org/10.1016/j.jddst.2019.02.017]

[56]
Poonia N, Kharb R, Lather V, Pandita D. Nanostructured lipid carriers: Versatile oral delivery vehicle. Future Sci OA  2016; 2(3): FSO135.
 [http://dx.doi.org/10.4155/fsoa-2016-0030] [PMID:  28031979]

[57]
Luan J, Zheng F, Yang X, Yu A, Zhai G. Nanostructured lipid carriers for oral delivery of baicalin: in vitro and in vivo evaluation. Colloids Surf A Physicochem Eng Asp  2015; 466: 154-9.
 [http://dx.doi.org/10.1016/j.colsurfa.2014.11.015]

[58]
Wang Q, Cheng H, Zhou K, et al. Nanostructured lipid carriers as a delivery system of biochanin A. Drug Deliv  2013; 20(8): 331-7.
 [http://dx.doi.org/10.3109/10717544.2013.838716] [PMID:  24111887]

[59]
Zhang T, Chen J, Zhang Y, Shen Q, Pan W. Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide. Eur J Pharm Sci  2011; 43(3): 174-9.
 [http://dx.doi.org/10.1016/j.ejps.2011.04.005] [PMID:  21530654]

[60]
Chaudhary S, Garg T, Murthy RSR, Rath G, Goyal AK. Development, optimization and evaluation of long chain nanolipid carrier for hepatic delivery of silymarin through lymphatic transport pathway. Int J Pharm  2015; 485(1-2): 108-21.
 [http://dx.doi.org/10.1016/j.ijpharm.2015.02.070] [PMID:  25735668]

[61]
Hejri A, Khosravi A, Gharanjig K, Hejazi M. Optimisation of the formulation of β-carotene loaded nanostructured lipid carriers prepared by solvent diffusion method. Food Chem  2013; 141(1): 117-23.
 [http://dx.doi.org/10.1016/j.foodchem.2013.02.080] [PMID:  23768336]

[62]
Sun B, Luo C, Li L, et al. Core-matched encapsulation of an oleate prodrug into nanostructured lipid carriers with high drug loading capability to facilitate the oral delivery of docetaxel. Colloids Surf B Biointerfaces  2016; 143: 47-55.
 [http://dx.doi.org/10.1016/j.colsurfb.2016.02.065] [PMID:  27011346]

[63]
Zhang X, Qiao H, Zhang T, Shi Y, Ni J. Enhancement of gastrointestinal absorption of isoliquiritigenin by nanostructured lipid carrier. Adv Powder Technol  2014; 25(3): 1060-8.
 [http://dx.doi.org/10.1016/j.apt.2014.02.012]

[64]
Huang J, Wang Q, Li T, Xia N, Xia Q. Nanostructured lipid carrier (NLC) as a strategy for encapsulation of quercetin and linseed oil: Preparation and in vitro characterization studies. J Food Eng  2017; 215: 1-12.
 [http://dx.doi.org/10.1016/j.jfoodeng.2017.07.002]

[65]
Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A. Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers. Drug Des Devel Ther  2017; 11: 771-82.
 [http://dx.doi.org/10.2147/DDDT.S123939] [PMID:  28352153]

[66]
Shah NV, Seth AK, Balaraman R, Aundhia CJ, Maheshwari RA, Parmar GR. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study. J Adv Res  2016; 7(3): 423-34.
 [http://dx.doi.org/10.1016/j.jare.2016.03.002]

[67]
Madane RG, Mahajan HS. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: Design, characterization, and in vivo study. Drug Deliv  2016; 23(4): 1326-34.
 [http://dx.doi.org/10.3109/10717544.2014.975382] [PMID:  25367836]

[68]
Thatipamula R, Palem C, Gannu R, Mudragada S, Yamsani M. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. Daru  2011; 19(1): 23-32.
 [PMID:  22615636]

[69]
Carbone C, Campisi A, Musumeci T, Raciti G, Bonfanti R, Puglisi G. FA-loaded lipid drug delivery systems: Preparation, characterization and biological studies. Eur J Pharm Sci  2014; 52: 12-20.
 [http://dx.doi.org/10.1016/j.ejps.2013.10.003] [PMID:  24514450]

[70]
How CW, Rasedee A, Manickam S, Rosli R. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: Characterization, stability assessment and cytotoxicity. Colloids Surf B Biointerfaces  2013; 112: 393-9.
 [http://dx.doi.org/10.1016/j.colsurfb.2013.08.009] [PMID:  24036474]

[71]
Choi KO, Choe J, Suh S, Ko S. Positively charged nanostructured lipid carriers and their effect on the dissolution of poorly soluble drugs. Molecules  2016; 21(5): E672.
 [http://dx.doi.org/10.3390/molecules21050672] [PMID:  27213324]

[72]
Severino P, Souto EB, Pinho SC, Santana MHA. Hydrophilic coating of mitotane-loaded lipid nanoparticles: Preliminary studies for mucosal adhesion. Pharm Dev Technol  2013; 18(3): 577-81.
 [http://dx.doi.org/10.3109/10837450.2011.614250] [PMID:  21958059]

[73]
Sato MR, Oshiro Junior JA, Machado RTA, et al. Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis. Drug Des Devel Ther  2017; 11: 909-21.
 [http://dx.doi.org/10.2147/DDDT.S127048] [PMID:  28356717]

[74]
Abdelwahab SI, Sheikh BY, Taha MME, et al. Thymoquinone-loaded nanostructured lipid carriers: Preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration. Int J Nanomed  2013; 8: 2163-72.
 [http://dx.doi.org/10.2147/IJN.S44108] [PMID:  23818776]

[75]
Chen CC, Tsai TH, Huang ZR, Fang JY. Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: Physicochemical characterization and pharmacokinetics. Eur J Pharm Biopharm  2010; 74(3): 474-82.
 [http://dx.doi.org/10.1016/j.ejpb.2009.12.008] [PMID:  20060469]

[76]
Abdelbary G, Haider M. In vitro characterization and growth inhibition effect of nanostructured lipid carriers for controlled delivery of methotrexate. Pharm Dev Technol  2013; 18(5): 1159-68.
 [http://dx.doi.org/10.3109/10837450.2011.614251] [PMID:  21958084]

[77]
Pereira RR, Testi M, Rossi F, et al. Ucuùba (Virola surinamensis) fat-based nanostructured lipid carriers for nail drug delivery of ketoconazole: Development and optimization using box-behnken design. Pharmaceutics  2019; 11(6): E284.
 [http://dx.doi.org/10.3390/pharmaceutics11060284] [PMID:  31212993]

[78]
Khan S, Baboota S, Ali J, Khan S, Narang RS, Narang JK. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs. Int J Pharm Investig  2015; 5(4): 182-91.
 [http://dx.doi.org/10.4103/2230-973X.167661] [PMID:  26682188]

[79]
Beloqui A, Solinís MA, Delgado A, Évora C, Isla A, Rodríguez-Gascón A. Fate of nanostructured lipid carriers (NLCs) following the oral route: Design, pharmacokinetics and biodistribution. J Microencapsul  2014; 31(1): 1-8.
 [http://dx.doi.org/10.3109/02652048.2013.788090] [PMID:  23631381]

[80]
Tran TH, Ramasamy T, Truong DH, Choi HG, Yong CS, Kim JO. Preparation and characterization of fenofibrate-loaded nanostructured lipid carriers for oral bioavailability enhancement. AAPS PharmSciTech  2014; 15(6): 1509-15.
 [http://dx.doi.org/10.1208/s12249-014-0175-y] [PMID:  25035071]

[81]
Patil GB, Patil ND, Deshmukh PK, Patil PO, Bari SB. Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach. Artif Cells Nanomed Biotechnol  2016; 44(1): 12-9.
 [http://dx.doi.org/10.3109/21691401.2014.909820] [PMID:  24866725]

[82]
Neupane YR, Srivastava M, Ahmad N, Kumar N, Bhatnagar A, Kohli K. Lipid based nanocarrier system for the potential oral delivery of decitabine: Formulation design, characterization, ex vivo, and in vivo assessment. Int J Pharm  2014; 477(1-2): 601-12.
 [http://dx.doi.org/10.1016/j.ijpharm.2014.11.001] [PMID:  25445972]

[83]
Li F, Weng Y, Wang L, He H, Yang J, Tang X. The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers. Int J Pharm  2010; 393(1-2): 203-11.
 [http://dx.doi.org/10.1016/j.ijpharm.2010.04.005] [PMID:  20385221]

[84]
Ganesan P, Ko HM, Kim IS, Choi DK. Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models. Int J Nanomedicine  2015; 10: 6757-72.
 [http://dx.doi.org/10.2147/IJN.S93918] [PMID:  26604750]

[85]
Negi LM, Talegaonkar S, Jaggi M, et al. Surface engineered nanostructured lipid carriers for targeting MDR tumor: Part II. in vivo biodistribution, pharmacodynamic and hematological toxicity studies. Colloids Surf B Biointerfaces  2014; 123: 610-5.
 [http://dx.doi.org/10.1016/j.colsurfb.2014.09.061] [PMID:  25454755]

[86]
Khajavinia A, Varshosaz J, Dehkordi AJ. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin. Nanotechnology  2012; 23(40): 405101.
 [http://dx.doi.org/10.1088/0957-4484/23/40/405101] [PMID:  22983592]

[87]
Etxebeste-Mitxeltorena M, Moreno E, Carvalheiro M, et al. Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis. ACS Infect Dis  2021; 7(12): 3197-209.
 [http://dx.doi.org/10.1021/acsinfecdis.1c00394] [PMID:  34767359]

[88]
Zhang YW, Tu LL, Zhang Y, Pan JC, Zheng GL, Yin LN. Liver-targeted delivery of asiatic acid nanostructured lipid carrier for the treatment of liver fibrosis. Drug Deliv  2021; 28(1): 2534-47.
 [http://dx.doi.org/10.1080/10717544.2021.2008054] [PMID:  34854788]

[89]
Sun M, Nie S, Pan X, Zhang R, Fan Z, Wang S. Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro. Colloids Surf B Biointerfaces  2014; 113: 15-24.
 [http://dx.doi.org/10.1016/j.colsurfb.2013.08.032] [PMID:  24060926]

[90]
Silva EL, Carneiro G, Caetano PA, et al. Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid. Expert Rev Anticancer Ther  2015; 15(2): 247-56.
 [http://dx.doi.org/10.1586/14737140.2015.1000868] [PMID:  25611812]

[91]
Bonaccorso A, Cimino C, Manno DE, et al. Essential oil-loaded nlc for potential intranasal administration. Pharmaceutics  2021; 13(8): 1166.
 [http://dx.doi.org/10.3390/pharmaceutics13081166] [PMID:  34452126]

[92]
Chinsriwongkul A, Chareanputtakhun P, Ngawhirunpat T, et al. Nanostructured lipid carriers (NLC) for parenteral delivery of an anticancer drug. AAPS PharmSciTech  2012; 13(1): 150-8.
 [http://dx.doi.org/10.1208/s12249-011-9733-8] [PMID:  22167418]

[93]
Mahoutforoush A, Solouk A, Hamishehkar H, Haghbin Nazarpak M, Abbaspour-Ravasjani S. Novel decorated nanostructured lipid carrier for simultaneous active targeting of three anti-cancer agents. Life Sci  2021; 279: 119576.
 [http://dx.doi.org/10.1016/j.lfs.2021.119576] [PMID:  33965376]

[94]
Jiang T, Ma S, Shen Y, Li Y, Pan R, Xing H. Topical anesthetic and pain relief using penetration enhancer and transcriptional transactivator peptide multi-decorated nanostructured lipid carriers. Drug Deliv  2021; 28(1): 478-86.
 [http://dx.doi.org/10.1080/10717544.2021.1889717] [PMID:  33641554]

[95]
Rodrigues da Silva GH, Geronimo G, García-López JP, et al. Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish. Sci Rep  2020; 10(1): 19733.
 [http://dx.doi.org/10.1038/s41598-020-76751-6] [PMID:  33184457]

[96]
Al-Qushawi A, Rassouli A, Atyabi F, et al. Preparation and characterization of three tilmicosin-loaded lipid nanoparticles: Physicochemical properties and in vitro antibacterial activities. Iran J Pharm Res  2016; 15(4): 663-76.
 [PMID:  28261309]

[97]
Kaur P, Garg T, Rath G, Murthy RSR, Goyal AK. 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 Deliv  2016; 23(6): 1912-25.
 [http://dx.doi.org/10.3109/10717544.2014.993486] [PMID:  25544602]

[98]
Khalil RM, Abd-Elbary A, Kassem MA, Ghorab MM, Basha M. Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam. Pharm Dev Technol  2014; 19(3): 304-14.
 [http://dx.doi.org/10.3109/10837450.2013.778872] [PMID:  23528038]

[99]
Grumezescu AM. Nanobiomaterials in galenic formulations and cosmetics: Applications of nanobiomaterials. New York: William Andrew 2016.

[100]
Chen Y, Zhou L, Yuan L, Zhang ZH, Liu X, Wu Q. Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers. Int J Nanomedicine  2012; 7: 3023-32.
 [http://dx.doi.org/10.2147/IJN.S32476] [PMID:  22787398]

[101]
Vairo C, Collantes M, Quincoces G, et al. Preclinical safety of topically administered nanostructured lipid carriers (NLC) for wound healing application: Biodistribution and toxicity studies. Int J Pharm  2019; 569: 118484.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118484] [PMID:  31260785]

[102]
Garg NK, Tandel N, Bhadada SK, Tyagi RK. Nanostructured lipid carrier-mediated transdermal delivery of aceclofenac hydrogel present an effective therapeutic approach for inflammatory diseases. Front Pharmacol  2021; 12: 713616.
 [http://dx.doi.org/10.3389/fphar.2021.713616] [PMID:  34616297]

[103]
Chakole CM, Chauhan MK. Research progress of nanostructured lipid carriers in ocular drug delivery. Drug Deliv Lett  2021; 11(3): 203-19.
 [http://dx.doi.org/10.2174/2210303111666210212143011]

[104]
Youssef A, Dudhipala N, Majumdar S. Ciprofloxacin loaded nanostructured lipid carriers incorporated into in-situ gels to improve management of bacterial endophthalmitis. Pharmaceutics  2020; 12(6): E572.
 [http://dx.doi.org/10.3390/pharmaceutics12060572] [PMID:  32575524]

[105]
Lakhani P, Patil A, Wu KW, et al. Optimization, stabilization, and characterization of amphotericin B loaded nanostructured lipid carriers for ocular drug delivery. Int J Pharm  2019; 572: 118771.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118771] [PMID:  31669555]

[106]
Üner M, Yener G, Ergüven M. Design of colloidal drug carriers of celecoxib for use in treatment of breast cancer and leukemia. Mater Sci Eng C  2019; 103: 109874.
 [http://dx.doi.org/10.1016/j.msec.2019.109874] [PMID:  31349508]

[107]
Tortorella S, Karagiannis TC. Transferrin receptor-mediated endocytosis: A useful target for cancer therapy. J Membr Biol  2014; 247(4): 291-307.
 [http://dx.doi.org/10.1007/s00232-014-9637-0] [PMID:  24573305]

[108]
Zhang B, Zhang Y, Yu D. Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery. Oncol Rep  2017; 37(2): 937-44.
 [http://dx.doi.org/10.3892/or.2016.5298] [PMID:  27959442]

[109]
Dos Santos Rodrigues B, Lakkadwala S, Kanekiyo T, Singh J. Development and screening of brain-targeted lipid-based nanoparticles with enhanced cell penetration and gene delivery properties. Int J Nanomedicine  2019; 14: 6497-517.
 [http://dx.doi.org/10.2147/IJN.S215941] [PMID:  31616141]

[110]
Hsueh YS, Shyong YJ, Yu HC, et al. Nanostructured lipid carrier gel formulation of recombinant human thrombomodulin improve diabetic wound healing by topical administration. Pharmaceutics  2021; 13(9): 1386.
 [http://dx.doi.org/10.3390/pharmaceutics13091386] [PMID:  34575462]

[111]
Nordin N, Yeap SK, Zamberi NR, et al. Characterization and toxicity of citral incorporated with nanostructured lipid carrier. PeerJ  2018; 6: e3916.
 [http://dx.doi.org/10.7717/peerj.3916] [PMID:  29312812]

[112]
Jaiswal P, Gidwani B, Vyas A. Nanostructured lipid carriers and their current application in targeted drug delivery. Artif Cells Nanomed Biotechnol  2016; 44(1): 27-40.
 [http://dx.doi.org/10.3109/21691401.2014.909822] [PMID:  24813223]

[113]
Rodrigues da Silva GH, Moura LD, Carvalho FV, et al. Antineoplastics encapsulated in nanostructured lipid carriers. Molecules  2021; 26(22): 6929.
 [http://dx.doi.org/10.3390/molecules26226929] [PMID:  34834022]

[114]
Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: A review. Pharmaceutics  2020; 12(3): E288.
 [http://dx.doi.org/10.3390/pharmaceutics12030288] [PMID:  32210127]

[115]
Tapeinos C, Battaglini M, Ciofani G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release  2017; 264: 306-32.
 [http://dx.doi.org/10.1016/j.jconrel.2017.08.033] [PMID:  28844756]

[116]
Tongqian C, Chandra V, Kurt V, Weimin W, Zhang YE. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules. 2008.

[117]
Cornelia K, Marc M. Nanonized testosterone formulations for improved bioavailability. 2010.

[118]
Ulagaraj SC. Solid nanoparticle formulation of water insoluble
pharmaceutical substances with reduced ostwald ripening. European Patent EP2054036B1, 2009.

[119]
ROLF P. Nanocrystals for use in topical cosmetic formulations and
method of production thereof. U.S. Patent No. 9,114,077, 2015.

[120]
Luisa BM, Gaetano G, Fabiola CE, Filippo D. Nanostructured lipid
carriers containing riluzole and phamaceutical formulations containing
said particles. U.S. Patent Application No. 12/308,932, 2010.

[121]
Ka-Wang WK, Jonathan W, Jared VG, Frank LS. Antibody bound
synthetic vesicle containing molecules for deliver to central and peripheral
nervous system cells. US Patent US20110097392A1, 2011.

[122]
Lluis VPJ, Raquel DG, Alfonso FB. Lipid nanoparticle capsules. U.S. Patent Application No. 13/636,909, 2013.

[123]
Arma T, Sulaiman RH, Bustamam AA, Wunhow C, Yeap SK. A composition for treating leukemia. WO2014123406A1, 2014.

[124]
Duran CNE, Pinto DAX. Method for producing nanostructured
lipid carriers on triblock copolymers, nanostructured lipid carriers
thereby produced, and uses thereof. WO/2016/065444, 2016.

[125]
Cheng Z, Ling Hui, Jingming Z, Taoyan Mao. Nanostructure lipid
carrier coated with sun-screening agent and preparation method and
application thereof. CN 107349116 A, 2017.

[126]
Cuiyan HAN, Shanshan Jin, MA Xiaoxing, Chang Liu, Cheng Y, Xiaoyu SUI, et al. Roxithromycin-loaded nanostructure lipid carrier
gel and preparation method thereof. CN 105534881 A, 2016.

[127]
Domenico F, Jonathan C, Leana R, Keegan M. Nanostructure lipid
carrier delivery system, composition, and methods. WO 2021/168573 A1, 2021.

[128]
Qing Y, Jinxi N, Ning Cai, Y Ling, Shuang Li. Pulullan-modified ginsenoside Rg3 nanostructure lipid carrier and preparation method
thereof. CN 113262310 A, 2021.

[129]
Khan AA, Mudassir J, Akhtar S, Murugaiyah V, Darwis Y. Freeze-dried lopinavir-loaded nanostructured lipid carriers for enhanced cellular uptake and bioavailability: Statistical optimization, in vitro and in vivo evaluations. Pharmaceutics  2019; 11(2): E97.
 [http://dx.doi.org/10.3390/pharmaceutics11020097] [PMID:  30823545]

[130]
Anwar W, Dawaba HM, Afouna MI, Samy AM, Rashed MH, Abdelaziz AE. Enhancing the oral bioavailability of candesartan cilexetil loaded nanostructured lipid carriers: In vitro characterization and absorption in rats after oral administration. Pharmaceutics  2020; 12(11): E1047.
 [http://dx.doi.org/10.3390/pharmaceutics12111047] [PMID:  33142816]
Cite As
Recent Patents on Nanotechnology

A Detailed Insight into Nanostructured Lipid Carriers: A Versatile Drug Delivery System

Abstract

Graphical Abstract
