Lipid Carriers: Role and Applications in Nano Drug Delivery

  • Naveen Chella
  • Nalini R. ShastriEmail author


The ability of lipid carriers to enhance solubility, absorption and thereby the bioavailability of poorly soluble molecules by selective mechanism makes these systems a unique delivery option for certain classes of drugs. Different types of delivery systems that include liposome, solid lipid nanoparticles, nanostructured lipid carriers, lipid–polymer hybrid nanoparticles, lipoplexes, and phytosomes can be produced depending on the lipids/excipients used and the formulation technique employed. In this chapter, focus will be on different lipid-based carrier systems, their role in nano delivery and the advantages offered in improvement of solubility, absorption, and bioavailability with relevant case studies. Manufacturing methods of different carrier systems will be elaborated with a brief overview of scale up feasibility. Gene delivery with the use of charged lipids and delivery of herbal actives and neutraceuticals by phytosomes will be presented. Commercial products based on the lipid technology and recent patents in this area will be discussed.


Lipid carriers Drug delivery Solid lipid nanoparticles Liposomes Phytosome Gene delivery 



Biopharmaceutics classification system




Generally regarded as safe


High-pressure homogenization


Lipid polymer hybrid nanoparticles


Large unilamellar vesicles


Multilamellar vesicles


Nanostructured lipid carriers


Polyethylene glycol




Reticuloendothelial system


Supercritical fluid


Supercritical fluid extraction of emulsions


Solid lipid nanoparticles


Small unilamellar vesicles


  1. Aditya NP, Macedo AS, Doktorovova S et al (2014) 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). LWT—Food Sci Technol 59(1):115–121CrossRefGoogle Scholar
  2. Agrawal U, Chashoo G, Sharma PR et al (2015) Tailored polymer-lipid hybrid nanoparticles for the delivery of drug conjugate: dual strategy for brain targeting. Colloids Surf B 126:414–425CrossRefGoogle Scholar
  3. Ahmad I, Longenecker M, Samuel J, Allen TM (1993) Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. Cancer Res 53(7):1484–1488PubMedGoogle Scholar
  4. Aji Alex MR, Chacko AJ, Jose S, Souto EB (2011) Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci 42(1–2):11–18Google Scholar
  5. Akbarzadeh A, Rezaei-Sadabady R, Davaran S et al (2013) Liposome: classification, preparation, and applications. Nanoscale Res Lett 8(1):102PubMedPubMedCentralCrossRefGoogle Scholar
  6. Ali SO, Darwish HAE-m, Ismail NAE-f (2014) Modulatory effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced liver cirrhosis in rats. Chem Biol Interact 216:26–33Google Scholar
  7. Alyautdin RN, Petrov VE, Langer K et al (1997) Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res 14(3):325–328PubMedCrossRefGoogle Scholar
  8. Amidon GL, Lennernäs H, Shah VP, Crison JR (1995) A Theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12(3):413–420PubMedCrossRefGoogle Scholar
  9. Ana Rute N, Joana Fontes Q, Babette W et al (2015) Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E. Nanotechnology 26(49):495103CrossRefGoogle Scholar
  10. Araújo J, Garcia ML, Mallandrich M, Souto EB, Calpena AC (2012) Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in vitro and ex vivo studies. Nanomed Nanotech Biol Med 8(6):1034–1041Google Scholar
  11. Baek J-S, Cho C-W (2015) Controlled release and reversal of multidrug resistance by co-encapsulation of paclitaxel and verapamil in solid lipid nanoparticles. Int J Pharm 478(2):617–624PubMedCrossRefGoogle Scholar
  12. Bally MB, Mayer LD, Loughrey H et al (1988) Dopamine accumulation in large unilamellar vesicle systems induced by transmembrane ion gradients. Chem Phys Lipids 47(2):97–107PubMedCrossRefGoogle Scholar
  13. Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13(1):238–252PubMedCrossRefGoogle Scholar
  14. Bangham AD, Standish MM, Watkins JC, Weissmann G (1967) The diffusion of ions from a phospholipid model membrane system. Protoplasma 63(1):183–187PubMedCrossRefGoogle Scholar
  15. Battaglia L, Gallarate M, Panciani PP et al (2014) Techniques for the preparation of solid lipid nano and microparticles. In: Sezer AD (ed) Nanotechnology and nanomaterials—application of nanotechnology in drug delivery. pp 51–75Google Scholar
  16. Batzri S, Korn ED (1973) Single bilayer liposomes prepared without sonication. Biochimica et Biophysica Acta (BBA). Biomembranes 298(4):1015–1019CrossRefGoogle Scholar
  17. Bombardelli E, Spelta M (1991) Phospholipid-polyphenol complexes: a new concept in skin care ingredients. Cosmet Toiletries 106(3):69–76Google Scholar
  18. Bombardelli E, Spelta M, Della Loggia R, Sosa S, Tubaro A (1991) Aging skin: protective effect of Silymarin Phytosome®. Fitoterapia 62:115–122Google Scholar
  19. Bombardelli E, Cristoni A, Morazzoni P (1994) Phytosomes in functional cosmetics. Fitoterapia 65:387–401Google Scholar
  20. Bondì ML, Azzolina A, Craparo EF et al (2014) Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells. J Nanobiotechnol 12(1):1–9CrossRefGoogle Scholar
  21. Buñuales María, Düzgüne Nejat, Zalba Sara et al (2011) Efficient gene delivery by EGF-lipoplexes in vitro and in vivo. Nanomedicine 6(1):89–98PubMedCrossRefGoogle Scholar
  22. Cannon JB (2014) Lipids in transdermal and topical drug delivery. Am Pharm RevGoogle Scholar
  23. Cardoso AL, Simoes S, de Almeida LP et al (2008) Tf-lipoplexes for neuronal siRNA delivery: a promising system to mediate gene silencing in the CNS. J Control Release 132(2):113–123PubMedCrossRefGoogle Scholar
  24. Chan JM, Zhang L, Yuet KP, Liao G et al (2009) PLGA–lecithin–PEG core–shell nanoparticles for controlled drug delivery. Biomaterials 30(8):1627–1634PubMedCrossRefGoogle Scholar
  25. Charcosset C, El-Harati A, Fessi H (2005) Preparation of solid lipid nanoparticles using a membrane contactor. J Control Release 108(1):112–120PubMedCrossRefGoogle Scholar
  26. Chattopadhyay P, Shekunov BY, Yim D et al (2007) Production of solid lipid nanoparticle suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system. Adv Drug Deliv Rev 59(6):444–453PubMedCrossRefGoogle Scholar
  27. Chen H, Chang X, Du D et al (2006) Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J Control Release 110(2):296–306PubMedCrossRefGoogle Scholar
  28. Chen Y, Lu Y, Chen J et al (2009) Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int J Pharm 376(1–2):153–160PubMedCrossRefGoogle Scholar
  29. Chen ZP, Sun J, Chen HX et al (2010) Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of Ginkgo biloba extracts, Ginkgo biloba extract phospholipid complexes and Ginkgo biloba extract solid dispersions inrats. Fitoterapia 81:10145–10152)Google Scholar
  30. Chen M, Gupta V, Anselmo AC et al (2014) Topical delivery of hyaluronic acid into skin using SPACE-peptide carriers. J Control Release 173:67–74PubMedCrossRefGoogle Scholar
  31. Cheng WWK, Allen TM (2008) Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a comparison of whole monoclonal antibody, Fab′ fragments and single chain Fv. J Control Release 126(1):50–58PubMedCrossRefGoogle Scholar
  32. Choudhari KB, Labhasetwar V, Dorle AK (1994) Liposomes as a carrier for oral admnistration of insulin: effect of formulation factors. J Microencapsul 11(3):319–325Google Scholar
  33. (2007) The effect of high-dose silybin-phytosome in men with prostate cancer. Accessed on 28 Jan 2016
  34. (2014) A phase II study to assess efficacy of combined treatment with Erlotinib (Tarceva) and Silybin-phytosome (Siliphos) in patients with EGFR mutant lung adenocarcinoma.
  35. (2015) Effects of Greenselect Phytosome® on weight maintenance after weight loss in obese women. Accessed on Jan 2016
  36. Daniels TR, Bernabeu E, Rodríguez JA et al (2012) The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta 1820(3):291–317Google Scholar
  37. Deamer DW (2010) From “banghasomes” to liposomes: a memoir of Alec Bangham, 1921–2010. FASEB J 24(5):1308–1310PubMedCrossRefGoogle Scholar
  38. Duarte S, Faneca H, Lima MC (2012) Folate-associated lipoplexes mediate efficient gene delivery and potent antitumoral activity in vitro and in vivo. Int J Pharm 423(2):365–377PubMedCrossRefGoogle Scholar
  39. Ekambaram P, Abdul HSA (2011) Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm 3(3):216–220PubMedPubMedCentralCrossRefGoogle Scholar
  40. El-Gazayerly ON, Makhlouf AI, Soelm AM, Mohmoud MA (2014) Antioxidant and hepatoprotective effects of silymarin phytosomes compared to milk thistle extract in CCl4 induced hepatotoxicity in rats. J Microencapsul 31(1):23–30PubMedCrossRefGoogle Scholar
  41. Elhissi AMA, Dennison SR, Ahmed W et al (2014) New delivery systems—liposomes for pulmonary delivery of antibacterial drugs. In: Novel antimicrobial agents and strategies. Wiley. KGaA, pp 387–406Google Scholar
  42. Elouahabi A, Ruysschaert J-M (2005) Formation and intracellular trafficking of lipoplexes and polyplexes. Mol Ther 11(3):336–347PubMedCrossRefGoogle Scholar
  43. Fang G, Tang B, Chao Y et al (2015) Cysteine-functionalized nanostructured lipid carriers for oral delivery of docetaxel: a permeability and pharmacokinetic study. Mol Pharm 12(7):2384–2395PubMedCrossRefGoogle Scholar
  44. Felgner PL, Gadek TR, Holm M et al (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84(21):7413–7417PubMedPubMedCentralCrossRefGoogle Scholar
  45. Flaig TW, Glode M, Gustafson D et al (2010) A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate 70(8):848–855PubMedGoogle Scholar
  46. Fonte P, Nogueira T, Gehm C et al (2011) Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin. Drug Deliv Transl Res 1(4):299–308PubMedCrossRefGoogle Scholar
  47. Freag MS, Elnaggar YSR, Abdallah OY (2013) Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation. IntJ Nanomed 8:2385–2397Google Scholar
  48. Garcı́a-Fuentes M, Torres D, Alonso MJ (2003) Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloids Surf B 27(2–3):159–168Google Scholar
  49. Garg Tarun, Goya AK (2014) Liposomes: targeted and controlled delivery system. Drug Delivery Lett 4:62–71CrossRefGoogle Scholar
  50. Gasco MR (1993) Method for producing solid lipid microspheres having a narrow size distribution. Google PatentsGoogle Scholar
  51. Gaspar DP, Faria V, Gonçalves LMD et al (2016) Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies. Int J Pharm 497(1–2):199–209PubMedCrossRefGoogle Scholar
  52. Gopal V, Prasad TK, Rao NM et al (2006) Synthesis and in vitro evaluation of glutamide-containing cationic lipids for gene delivery. Bioconjug Chem 17(6):1530–1536PubMedCrossRefGoogle Scholar
  53. GRAS substances database. (1972–1980) U.S. FDA. Accessed Jan 2016
  54. Gregoriadis G, Ryman BE (1971) Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochem J 124(5):58PPubMedPubMedCentralCrossRefGoogle Scholar
  55. Gubernator J (2011) Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increased in vivo activity. Expert Opin Drug Deliv 8(5):565–580PubMedCrossRefGoogle Scholar
  56. Guo X, Gagne L, Chen H, Szoka FC (2014) Novel ortho ester-based, pH-sensitive cationic lipid for gene delivery in vitro and in vivo. J Liposome Res 24(2):90–98PubMedCrossRefGoogle Scholar
  57. Hafeez A, Aqil M, Ali A (2015) Development and optimization of a nanostructured lipid carrier based gel formulation of Etoricoxib for topical delivery using Box-Behnken design. in vitro and ex vivo evaluation. Sci Adv Mater 7(8):1567–1580CrossRefGoogle Scholar
  58. Han F, Yin R, Che X et al (2012a) Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: design, characterization and in vivo evaluation. Int J Pharm 439(1-2):349–357.Google Scholar
  59. Han H-K, Shin H-J, Ha DH (2012b) Improved oral bioavailability of alendronate via the mucoadhesive liposomal delivery system. Eur J Pharm Sci 46(5):500–507PubMedCrossRefGoogle Scholar
  60. Hanato J, Kuriyama K, Mizumoto T et al (2009) Liposomal formulations of glucagon-like peptide-1: improved bioavailability and anti-diabetic effect. Int J Pharm 382(1–2):111–116PubMedCrossRefGoogle Scholar
  61. Haran G, Cohen R, Bar LK, Barenholz Y (1993) Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Bioch BiophysBiom 1151(2):201–215CrossRefGoogle Scholar
  62. Harde H, Das M, Jain S (2011) Solid lipid nanoparticles: an oral bioavailability enhancer vehicle. Expert Opin Drug Deliv 8(11):1407–1424PubMedCrossRefGoogle Scholar
  63. Hippalgaonkar K, Adelli GR, Hippalgaonkar K et al (2013) Indomethacin-loaded solid lipid nanoparticles for ocular delivery: development, characterization, and in vitro evaluation. J Ocul Pharmacol Ther 29(2):216–228PubMedPubMedCentralCrossRefGoogle Scholar
  64. Hu FQ, Yuan H, Zhang HH, Fang M (2002) Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm 239(1–2):121–128PubMedCrossRefGoogle Scholar
  65. Hüsch J, Bohnet J, Fricker G et al (2013) Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome®) of Boswellia extract. Fitoterapia 84:89–98PubMedCrossRefGoogle Scholar
  66. Ibrahim WM, AlOmrani AH, Yassin AEB (2014) Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability. Int J Nanomed 9:129–144Google Scholar
  67. Joshi MD, Müller RH (2009) Lipid nanoparticles for parenteral delivery of actives. Eur J Pharm Biopharm 71(2):161–172PubMedCrossRefGoogle Scholar
  68. Juliano RL, Lopez-Berestein G, Hopfer R et al (1985) Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections. Ann NY Acad Sci 446:390–402PubMedCrossRefGoogle Scholar
  69. Kakkar V, Singh S, Singla D, Kaur IP (2011) Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol Nutr Food Res 55(3):495–503PubMedCrossRefGoogle Scholar
  70. Kakkar S, Karuppayil SM, Raut JS et al (2015) Lipid-polyethylene glycol based nano-ocular formulation of ketoconazole. Int J Pharm 495(1):276–289PubMedCrossRefGoogle Scholar
  71. Kalam MA, Sultana Y, Ali A et al (2013) Part I: development and optimization of solid-lipid nanoparticles using Box-Behnken statistical design for ocular delivery of gatifloxacin. J Biomed Mater Res A 101A(6):1813–1827CrossRefGoogle Scholar
  72. Kidd PM (2009) Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev 14(3):226–246PubMedGoogle Scholar
  73. Kim BK, Seu YB, Bae YU et al (2014) Efficient delivery of plasmid DNA using cholesterol-based cationic lipids containing polyamines and ether linkages. Int J Mol Sci 15(5):7293–7312PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kirby C, Gregoriadis G (1984) Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Nat Biotech 2(11):979–984CrossRefGoogle Scholar
  75. Krishnamurthy S, Vaiyapuri R, Zhang L, Chan JM (2015) Lipid-coated polymeric nanoparticles for cancer drug delivery. Biomater Sci 3(7):923–936PubMedCrossRefGoogle Scholar
  76. Kubo T, Sugita T, Shimose S et al (2000) Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters. Int J Oncol 17(2):309–315PubMedGoogle Scholar
  77. Li B, Xu H, Li Z et al (2012) Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies. Int J Nanomedicine 7:187–197PubMedPubMedCentralGoogle Scholar
  78. Li J, Wang X, Zhang T et al (2015) A review on phospholipids and their main applications in drug delivery systems. Asian J Pharm Sci 10(2):81–98CrossRefGoogle Scholar
  79. Ling G, Zhang T, Zhang P, Sun J, He Z (2016) Nanostructured lipid-carrageenan hybrid carriers (NLCCs) for controlled delivery of mitoxantrone hydrochloride to enhance anticancer activity bypassing the BCRP-mediated efflux. Drug Dev Ind Pharm 42(8):1351–1359Google Scholar
  80. Liu R, Liu Z, Zhang C, Zhang B (2012) Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability. J Pharm Sci 101(10):3833–3844PubMedCrossRefGoogle Scholar
  81. Liu Y, Fang J, Kim Y-J, Wong MK, Wang P (2014) Codelivery of doxorubicin and paclitaxel by cross-linked multilamellar liposome enables synergistic antitumor activity. Mol Pharm 11(5):1651–1661PubMedPubMedCentralCrossRefGoogle Scholar
  82. Liu Y, Salituro GM, K-j Lee, Bak A, Leung HD (2015) Modulating drug release and enhancing the oral bioavailability of torcetrapib with solid lipid dispersion formulations. AAPS Pharm Sci Tech 16(5):1091–1100CrossRefGoogle Scholar
  83. Luan J, Zheng F, Yang X, Yu A, Zhai G (2015) Nanostructured lipid carriers for oral delivery of baicalin: in vitro and in vivo evaluation. Colloids Surf A Physicochem Eng Asp 466:154–159CrossRefGoogle Scholar
  84. Lucks S, Mueller R (1994) Medication vehicles made of solid lipid particles (solid lipid nanospheres - sln). Google PatentsGoogle Scholar
  85. Luo Y, Chen D, Ren L, Zhao X, Qin J (2006) Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Controlled Release 114(1):53–59CrossRefGoogle Scholar
  86. Lyass O, Uziely B, Ben-Yosef R et al (2000) Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer 89(5):1037–1047PubMedCrossRefGoogle Scholar
  87. Ma B, Zhang S, Jiang H, Zhao B, Lv H (2007) Lipoplex morphologies and their influences on transfection efficiency in gene delivery. J Control Release 123(3):184–194PubMedCrossRefGoogle Scholar
  88. Mahmood I, Green MD (2005) Pharmacokinetic and pharmacodynamic considerations in the development of therapeutic proteins. Clin Pharmacokinet 44(4):331–347PubMedCrossRefGoogle Scholar
  89. Maiti K, Mukherjee K, Gantait A et al (2006) Enhanced therapeutic potential of naringenin-phospholipid complex in rats. J Pharm Pharmacol 58(9):1227–1233PubMedCrossRefGoogle Scholar
  90. Maiti K, Mukherjee K, Murugan V et al (2010) Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome. J Sci Food Agric 90(1):43–51PubMedCrossRefGoogle Scholar
  91. Makwana V, Jain R, Patel K et al (2015) Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach. Int J Pharm 495(1):439–446PubMedCrossRefGoogle Scholar
  92. Manach C, Scalbert A, Morand C et al (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79(5):727–747PubMedGoogle Scholar
  93. Mandal B, Bhattacharjee H, Mittal N et al (2013) Core-shell-type lipid-polymer hybrid nanoparticles as a drug delivery platform. Nanomedicine 9(4):474–491PubMedCrossRefGoogle Scholar
  94. Manjunath K, Reddy JS, Venkateswarlu V (2005) Solid lipid nanoparticles as drug delivery systems. Methods Find Exp Clin Pharmacol 27(2):127–144PubMedCrossRefGoogle Scholar
  95. Martin B, Sainlos M, Aissaoui A et al (2005) The design of cationic lipids for gene delivery. Curr Pharm Des 11(3):375–394PubMedCrossRefGoogle Scholar
  96. Martins S, Silva AC, Ferreira DC, Souto EB (2009) Improving oral absorption of samon calcitonin by trimyristin lipid nanoparticles. J Biomed Nanotechnol 5(1):76–83PubMedCrossRefGoogle Scholar
  97. Mazumder A, Dwivedi A, du Preez JL, du Plessis J (2016) In vitro wound healing and cytotoxic effects of sinigrin–phytosome complex. Int J Pharm 498(1–2):283–293PubMedCrossRefGoogle Scholar
  98. Mehnert W, Mader K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47(2–3):165–196PubMedCrossRefGoogle Scholar
  99. Mhashilkar A, Chada S, Roth JA, Ramesh R (2001) Gene therapy: therapeutic approaches and implications. Biotechnol Adv 19(4):279–297PubMedCrossRefGoogle Scholar
  100. Mohr L, Yoon SK, Eastman SJ et al (2001) Cationic liposome-mediated gene delivery to the liver and to hepatocellular carcinomas in mice. Hum Gene Ther 12(7):799–809PubMedCrossRefGoogle Scholar
  101. Montenegro L, Lai F, Offerta A et al (2016) From nanoemulsions to nanostructured lipid carriers: a relevant development in dermal delivery of drugs and cosmetics. J Drug Del Sci Tech 32:100–112CrossRefGoogle Scholar
  102. Moreno-Sastre M, Pastor M, Esquisabel A et al (2016) Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm 498(1–2):263–273PubMedCrossRefGoogle Scholar
  103. MuÈller RH, MaÈder Karsten, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery-a review of the state of the art. Eur J PharmBiopharm 50:161–177CrossRefGoogle Scholar
  104. Mukherjee S, Ray S, Thakur RS (2009) Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci 71(4):349–358PubMedPubMedCentralCrossRefGoogle Scholar
  105. Mukherjee Pulok K, Harwansh Ranjit K, Bhattacharyya S (2015) Bioavailability of herbal products: approach toward improved pharmacokinetics. In: Mukherjee PK (ed) Evidence based validation of herbal medicine. Elsevier, UK, pp 217–245CrossRefGoogle Scholar
  106. Müller RH, Mader K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of the art. Eur J Pharm Biopharm 50(1):161–177PubMedCrossRefGoogle Scholar
  107. Müller RH, Radtke M, Wissing SA (2002) Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm 242(1–2):121–128PubMedCrossRefGoogle Scholar
  108. Müller RH, Shegokar R, M Keck C (2011) 20 Years of lipid nanoparticles (SLN & NLC): present state of development & industrial applications. Curr Drug Discov Technol 8(3):207–221Google Scholar
  109. Müller RH, Radtke M, Wissing SA (2002) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54(Supplement):S131–S155PubMedCrossRefGoogle Scholar
  110. Neves AR, Lúcio M, Martins S et al (2013) Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability. Int J Nanomed 8:177–187CrossRefGoogle Scholar
  111. Ohsawa T, Miura H, Harada K (1985) Improvement of encapsulation efficiency of water-soluble drugs in liposomes formed by the freeze-thawing method. Chem Pharm Bull 33(9):3945–3952PubMedCrossRefGoogle Scholar
  112. Olbrich C, Müller RH (1999) Enzymatic degradation of SLN—effect of surfactant and surfactant mixtures. Int J Pharm 180(1):31–39PubMedCrossRefGoogle Scholar
  113. Palange AL, Di Mascolo D, Carallo C et al (2014) Lipid-polymer nanoparticles encapsulating curcumin for modulating the vascular deposition of breast cancer cells. Nanomedicine 10(5):991–1002PubMedPubMedCentralCrossRefGoogle Scholar
  114. Panda VS, Naik SR (2008) Cardioprotective activity of ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation. Exp Toxicol Pathol 60(4–5):397–404PubMedCrossRefGoogle Scholar
  115. Papahadjopoulos D, Watkins JC (1967) Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. Biochim Biophys Acta 135(4):639–652PubMedCrossRefGoogle Scholar
  116. Pardeike J, Hommoss A, Müller RH (2009) Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. IntJ Pharm 366(1–2):170–184CrossRefGoogle Scholar
  117. Patil S, Joshi M, Pathak S et al (2012) Intravenous beta-artemether formulation (ARM NLC) as a superior alternative to commercial artesunate formulation. J Antimicrob Chemother 67(11):2713–2716PubMedCrossRefGoogle Scholar
  118. Patil H, Feng X, Ye X et al (2015) Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. The AAPS J 17(1):194–205PubMedCrossRefGoogle Scholar
  119. Patil-Gadhe A, Kyadarkunte A, Patole M, Pokharkar V (2014) Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance. Eur J Pharm Biopharm 88(1):169–177PubMedCrossRefGoogle Scholar
  120. Pignatello R, Carbone C, Puglia C et al (2015) Ophthalmic applications of lipid-based drug nanocarriers: an update of research and patenting activity. Ther Deliv 6(11):1297–1318PubMedCrossRefGoogle Scholar
  121. Radtke Magdalene, Souto Eliana B, Müller RH (2005) Nanostructured lipid carriers: a novel generation of solid lipid drug carriers. Pharm Tech Europe 17(4):45–50Google Scholar
  122. Raj R, Mongia P, Ram A, Jain NK (2015) Enhanced skin delivery of aceclofenac via hydrogel-based solid lipid nanoparticles. Artif Cells Nanomed Biotechnol. doi: 10.3109/21691401.2015.1036997 PubMedGoogle Scholar
  123. Safinya CR, Ewert KK, Majzoub RN, Leal C (2014) Cationic liposome-nucleic acid complexes for gene delivery and gene silencing. New J Chem 38(11):5164–5172PubMedPubMedCentralCrossRefGoogle Scholar
  124. Sakurai F, Inoue R, Nishino Y et al (2000) Effect of DNA/liposome mixing ratio on the physicochemical characteristics, cellular uptake and intracellular trafficking of plasmid DNA/cationic liposome complexes and subsequent gene expression. J Control Release 66(2–3):255–269PubMedCrossRefGoogle Scholar
  125. Sakurai F, Terada T, Maruyama M et al (2003) Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-beta gene and poly I: poly C in a murine lung metastasis model. Cancer Gene Ther 10(9):661–668PubMedCrossRefGoogle Scholar
  126. Salminen H, Helgason T, Aulbach S et al (2014) Influence of co-surfactants on crystallization and stability of solid lipid nanoparticles. J Colloid Interface Sci 426:256–263PubMedCrossRefGoogle Scholar
  127. Sarmento B, Martins S, Ferreira D, Souto EB (2007) Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomed 2(4):743–749Google Scholar
  128. Seyfoddin A, Al-Kassas R (2013) Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 39(4):508–519PubMedCrossRefGoogle Scholar
  129. Shi J, Xu Y, Xu X et al (2014) Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing. Nanomedicine 10(5):897–900PubMedPubMedCentralCrossRefGoogle Scholar
  130. Shrestha Hina, Bala Rajni, Arora S (2014) Lipid-based drug delivery systems. J Pharm 2014:10. doi: 10.1155/2014/801820 Google Scholar
  131. Siekmann B, Westesen K(1992) Submicron-sized parenteral carrier systems based on solid lipids. Pharm Pharmacol Lett 3:123–126Google Scholar
  132. Singh S, Singh M, Tripathi CB et al (2016) Development and evaluation of ultra-small nanostructured lipid carriers: novel topical delivery system for athlete’s foot. Drug Deliv Transl Res 6(1):38–47PubMedCrossRefGoogle Scholar
  133. Sjöström B, Bergenståhl B (1992) Preparation of submicron drug particles in lecithin-stabilized o/w emulsions I. Model studies of the precipitation of cholesteryl acetate. Int J Pharm 88(1–3):53–62CrossRefGoogle Scholar
  134. Solomon R, Gabizon AA (2008) Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal doxorubicin. Clinical Lymphoma Myeloma 8(1):21–32CrossRefGoogle Scholar
  135. Souto EB, Wissing SA, Barbosa CM, Müller RH (2004) Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery. Int J Pharm 278(1):71–77PubMedCrossRefGoogle Scholar
  136. Szoka F Jr, Papahadjopoulos D (1980) Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bio 9(1):467–508Google Scholar
  137. Takeuchi H, Kojima H, Yamamoto H, Kawashima Y (2001) Passive targeting of doxorubicin with polymer coated liposomes in tumor bearing rats. Biol Pharm Bull 24(7):795–799PubMedCrossRefGoogle Scholar
  138. Talsma H, van Steenbergen MJ, Borchert JC, Crommelin DJ (1994) A novel technique for the one-step preparation of liposomes and nonionic surfactant vesicles without the use of organic solvents. Liposome formation in a continuous gas stream: the ‘bubble’ method. J Pharm Sci 83(3):276–280Google Scholar
  139. Tamjidi F, Shahedi M, Varshosaz J, Nasirpour A (2013) Nanostructured lipid carriers (NLC): a potential delivery system for bioactive food molecules. Innov Food Sci Emerg Technol 19:29–43CrossRefGoogle Scholar
  140. Tang J, Zhang L, Gao H et al (2014) Co-delivery of doxorubicin and P-gp inhibitor by a reduction-sensitive liposome to overcome multidrug resistance, enhance anti-tumor efficiency and reduce toxicity. Drug Delivery, 1–14Google Scholar
  141. Taratula O, Kuzmov A, Shah M et al (2013) Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Rel 171(3):349–357CrossRefGoogle Scholar
  142. Tsukamoto T, Hironaka K, Fujisawa T et al (2013) Preparation of bromfenac-loaded liposomes modified with chitosan for ophthalmic drug delivery and evaluation of physicochemical properties and drug release profile. Asian J Pharm Sci 8(2):104–109CrossRefGoogle Scholar
  143. Tung NT, Huyen VT, Chi SC (2015) Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug. Arch Pharm Res 38(11):1999–2007PubMedCrossRefGoogle Scholar
  144. Uner M (2005) Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): Their benefits as colloidal drug carrier systems. Pharmazie 61(5):375–386Google Scholar
  145. Uner M (2006) Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): Their benefits as colloidal drug carrier systems. Pharmazie 61:375–386Google Scholar
  146. Ustundag-Okur N, Gokce EH, Bozbiyik DI et al (2014) Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis. Eur J Pharm Sci 63:204–215PubMedCrossRefGoogle Scholar
  147. van den Hoven JM, Hofkens W, Wauben MH et al (2011) Optimizing the therapeutic index of liposomal glucocorticoids in experimental arthritis. Int J Pharm 416(2):471–477PubMedCrossRefGoogle Scholar
  148. Venishetty VK, Chede R, Komuravelli R et al (2012) Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: a novel strategy to avoid intraduodenal administration. Colloids Surf B 95:1–9CrossRefGoogle Scholar
  149. Videira M, Almeida AJ, Fabra A (2012) Preclinical evaluation of a pulmonary delivered paclitaxel-loaded lipid nanocarrier antitumor effect. Nanomedicine 8(7):1208–1215PubMedCrossRefGoogle Scholar
  150. Vural I, Sarisozen C, Olmez SS (2011) Chitosan coated furosemide liposomes for improved bioavailability. J Biomed Nanotech 7(3):426–430CrossRefGoogle Scholar
  151. Vyas SP, Rai S, Paliwal R et al (2008) Solid lipid nanoparticles (SLNs) as a rising tool in drug delivery science: one step up in nanotechnology. Current Nanosci 4(1):30Google Scholar
  152. Wasungu L, Hoekstra D (2006) Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Release 116(2):255–264PubMedCrossRefGoogle Scholar
  153. Weber S, Zimmer A, Pardeike J (2014) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for pulmonary application: a review of the state of the art. Eur J Pharm Biopharm 86(1):7–22PubMedCrossRefGoogle Scholar
  154. Wissing SA, Kayser O, Muller RH (2004) Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 56(9):1257–1272PubMedCrossRefGoogle Scholar
  155. Wong HL, Bendayan R, Rauth AM et al (2006a) A mechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle system. J Pharm Exp Ther 317(3):1372–1381CrossRefGoogle Scholar
  156. Wong HL, Rauth AM, Bendayan R et al (2006b) A new polymer-lipid hybrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug-resistant human breast cancer cells. Pharm Res 23(7):1574–1585PubMedCrossRefGoogle Scholar
  157. Xu Y, Szoka FC Jr (1996) Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35(18):5616–5623PubMedCrossRefGoogle Scholar
  158. Yang T, Cui FD, Choi MK et al (2007) Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation. Int J Pharm 338(1–2):317–326PubMedCrossRefGoogle Scholar
  159. Yang C, Liu HZ, Fu ZX, Lu WD (2011) Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma. BMC Biotechnol 11:21PubMedPubMedCentralCrossRefGoogle Scholar
  160. Yang X, Liu Y, Liu C, Zhang N (2012) Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. J Biomed Nanotechn 8(5):834–842CrossRefGoogle Scholar
  161. Yang R, Zhang X, Li F et al (2013) Role of phospholipids and copolymers in enhancing stability and controlling degradation of intravenous lipid emulsions. Coll Surf A: PhysEng Asp 436:434–442CrossRefGoogle Scholar
  162. Yang T, Li B, Qi S et al (2014a) Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo. Theranostics 4(11):1096–1111PubMedPubMedCentralCrossRefGoogle Scholar
  163. Yang Y, Corona A 3rd, Schubert B et al (2014b) The effect of oil type on the aggregation stability of nanostructured lipid carriers. J Colloid Interface Sci 418:261–272PubMedCrossRefGoogle Scholar
  164. Yanyu X, Yunmei S, Zhipeng C, Qineng P (2006) The preparation of silybin–phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm 307:77–82PubMedCrossRefGoogle Scholar
  165. Yoo HS, Park TG (2004) Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin–PEG–folate conjugate. J Control Rel 100(2):247–256CrossRefGoogle Scholar
  166. Youshia J, Kamel AO, El Shamy A, Mansour S (2012) Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide. Int J Nanomed 7:2483–2496Google Scholar
  167. Yue Peng-Fei, Yuan Hai-Long, Yang Ming, Zhu WF (2009) Preparation, characterization and pharmacokinetics in vivo of oxymatrine phospholipid complex. J Bioequiv Availab 1:99–102CrossRefGoogle Scholar
  168. Zelphati O, Nguyen C, Ferrari M et al (1998) Stable and monodisperse lipoplex formulations for gene delivery. Gene Ther 5(9):1272–1282PubMedCrossRefGoogle Scholar
  169. Zhang L, Chan JM, Gu F et al (2008a) Self-assembled lipidpolymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano 2(8):1696–1702PubMedPubMedCentralCrossRefGoogle Scholar
  170. Zhang Y, Bradshaw-Pierce EL, Delille A et al (2008b) In vivo comparative study of lipid/DNA complexes with different in vitro serum stability: effects on biodistribution and tumor accumulation. J Pharm Sci 97(1):237–250PubMedCrossRefGoogle Scholar
  171. Zhang J, Tang Q, Xu X, Li N (2013) Development and evaluation of a novel phytosome-loaded chitosan microsphere system for curcumin delivery. Int J Pharm 448(1):168–174PubMedCrossRefGoogle Scholar
  172. Zhang J, Liu M-Q, Zhang J-L et al (2015) Biotinylated epidermal growth factor surface modified lipid nanoparticles to enhance the targeting efficiency in liver cancer therapy. J Biomater Tissue Eng 5(2):135–141CrossRefGoogle Scholar
  173. Zhang RX, Cai P, Zhang T et al (2016) Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin c and enable their spatiotemporal co-delivery and local bioavailability in breast tumor. Nanomedicine 12(5):1279–1290PubMedCrossRefGoogle Scholar
  174. Zhao L, Temelli F (2015) Preparation of liposomes using supercritical carbon dioxide via depressurization of the supercritical phase. J Food Engineering 158:104–112CrossRefGoogle Scholar
  175. Zhou X, Zhang X, Ye Y et al (2015) Nanostructured lipid carriers used for oral delivery of oridonin: An effect of ligand modification on absorption. Int J Pharm 479(2):391–398PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research (NIPER)Balanagar, HyderabadIndia

Personalised recommendations