In the past decade, research in the area of nanodrug delivery has reached a new height with the advent of lipid based nanodrug delivery systems. Lipids being biocompatible and possessing diverse physicochemical properties have tremendous potential to enhance oral bioavailability of water insoluble drugs. Incorporation of a drug in lipid carriers is a smart approach to overcome problems related with conventional oral therapy. In recent years, two lipid based nanoparticles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are widely explored. SLN are spherical nanoparticles with a drug-containing solid lipid core stabilized with surfactants and formulated mainly to improve bioavailability of the drug molecules. Despite several advantages of SLNs, their major drawbacks include limited drug loading, drug leakage, and crystallization during storage. These drawbacks were avoided or reduced by the development of a new generation of lipid nanoparticles, the NLC, wherein a solid lipid is blended with liquid lipid. Modulation of drug release was added advantage with NLC formulations. The present review focuses on production techniques, characterization, release characteristics, stability, toxicity and potential applications of SLNs and NLCs.
Similar content being viewed by others
References
S. Mukherjee, S. Ray, and R. S. Thakur, Indian J. Pharm. Sci., 71, 349 – 358 (2009).
R. H. Müller, K. Mäder, and S. Gohla, Eur. J. Pharm. Biopharm., 50, 161 – 177 (2000).
W. Mehnert and K. Mäder, Adv. Drug Deliv. Rev., 47, 165 – 196 (2001).
C. J. H. Porter and W. N. Charman, Adv. Drug Deliv. Rev., 50, 61 – 80 (2001).
R. Cavalli, M. R. Gasco, P. Chetoni, et al., Int. J. Pharm., 238, 241 – 245 (2002).
R. H. Müller,M. Radtke, and S. A. Wissing, Int. J. Pharm., 242, 121 – 128 (2002).
V. Jannin, J. Musakhanian, and D. Marchaud, Adv. Drug Deliv. Rev., 60(6), 734 – 746 (2008).
V. Patravale and P. Prabhu, in: Recent Trends in Novel Drug Delivery, N. Udupa and S. Mutalik (eds.), Prism Books Pvt. Ltd., Bengaluru (2014), pp. 81 – 167.
M. Üner and G. Yener, Int. J. Nanomedicine, 2(3), 289 – 300 (2007).
B. Siekmann and K. Westesen, Pharm. Pharmacol. Lett., 1, 123 – 126 (1992).
R. H. Müller and C. M. Keck, J. Biotech., 113(1 – 3), 151 – 170 (2004).
K. Manjunath and V. Venkateswarlu, J. Control. Release, 107, 215 – 228 (2005).
H. Weyhers, S. Ehlers, H. Hahn, et al., Pharmazie, 61(6), 539 – 544 (2006).
P. Severino, T. Andreani, A. S. Macedo, et al., J. Drug Deliv., 2012, 10 pages (2011).
K. Westesen, H. Bunjes, and M. H. J. Koch, J. Control. Release, 48(2 – 3), 223 – 236 (1997).
K. Westesen, B. Siekmann, and M. H. J. Koch, Int. J. Pharm., 93(1 – 3), 189 – 199 (1993).
H. Bunjes, K. Westesen, and M. H. J. Koch, Int. J. Pharm., 129(1 – 2), 159 – 173 (1996).
L. M. D. Gonçalves, F. Maestrelli, L. D. C. Mannelli, et al., Eur. J. Pharm. Biopharm., 102, 41 – 50 (2016).
L. Hu, Q. Xing, J. Meng, et al., AAPS PharmSciTech, 11(2), 582 – 587 (2010).
J. R. Madan, P. A. Khude, and K. Dua, Int. J. Pharm. Investig., 4(2), 60 – 64 (2014).
M. L. Bikkad, A. H. Nathani, S. K. Mandlik, et al., J. Liposome Res., 24(2), 113 – 123 (2014).
P. Chattopadhyay, B. Y. Shekunov, D. Yim, et al., Adv. Drug Deliv. Rev., 59(6), 444 – 453 (2007).
P. K. Gaur, S. Mishra, M. Bajpai, et al., Biomed. Res. Int., 2014, 9 (2014).
J. B. Prajapati, H. Katariya, and R. Patel, J. Drug Deliv. Sci. Technol., 43, 318 – 326 (2018).
V. Makwana, R. Jain, K. Patel, et al., Int. J. Pharm., 495(1), 439 – 446 (2015).
D. J. Jang, C. Moon, and E. Oh, Biomed. Pharmacother., 80, 162 – 172 (2016).
J. F. Fangueiro, E. Gonzalez-Mira, P. Martins-Lopes, et al., Pharm. Dev. Technol., 18(3), 545 – 549 (2013).
R. Parveen, F. J. Ahmad, Z. Iqbal, et al., Drug. Dev. Ind. Pharm., 40(9), 1206 – 1212 (2014).
P. Füredi, Z. E. Pápay, K. Kovács, et al., J. Pharm. Biomed. Anal., 132(5), 184 – 189 (2017).
M. Üner, S. A. Wissing, G. Yener, et al., Pharmazie, 59(4), 331 – 332 (2004).
V. Sandeep, D. Narendar, N. Arjun, et al., IJPSN, 9(6), 3524 – 3530 (2016).
S. Kumar, R. Narayan, V. Ahammed, et al., J. Drug Deliv. Sci. Technol., 44, 181 – 189 (2018).
J. Liu, W. Hu, H. Chen, et al., Int. J. Pharm., 328(2), 191 – 195 (2007).
S. M. Martins, B. Sarmento, C. Nunes, et al., Eur. J. Pharm. Biopharm., 85(3), 488 – 502 (2013).
J. S. Negi, P. Chattopadhyay, A. K. Sharma, et al., Eur. J. Pharm. Sci., 48, 231 – 239 (2013).
Y. C. Kuo and C. Y. S. Huang, J. Taiwan Inst. Chem. E., 45(4): 1154 – 1163 (2014).
H. F. Zhou, Q. H. Ma, Q. Xia, et al., Solid State Phenomena, 121 – 123, 271 – 274 (2007).
Y. C. Kuo, and S. J. Cheng, Int. J. Pharm., 499(1 – 2), 10 – 19 (2016).
R. Cavalli, O. Caputo, M. E. Carlotti, et al., Int. J. Pharm., 148, 47 – 54 (1997).
T. H. Tran, T. Ramasamy, H. J. Cho, et al., J. Nanosci. Nanotechnol., 14, 4820 – 4831 (2014).
T. H. Tran, J. Y. Choi, T. Ramasamy, et al., Carbohyd. Polym., 114, 407 – 415 (2014).
A. Narala and K. Veerabrahma, J. Pharm., 2013, 7 (2013).
R. B. Athawale, D. S. Jain, K. K. Singh, et al., Biomed. Pharmacother., 68(2), 231 – 240 (2014).
H. Wosicka-Fr1ckowiak, K. Cal, J. Stefanowska, et al., Int. J. Pharm., 495(2), 807 – 815 (2015).
J. Akbari, M. Saeedi, K. Morteza-Semnani, et al., Colloids Surf. B Biointerfaces, 145, 626 – 633 (2016).
I. Lacatusu, N. Badea, A. Murariu, et al., Soft Mater., 11(1), 75 – 84 (2013).
S. Barua, D. I. Lee, H. Kim, et al., Bull. Korean Chem. Soc., 39, 220 – 226 (2018).
P. Boonme, E. B. Souto, N. Wuttisantikul, et al., Eur J Lipid Sci Technol, 115(7), 820 – 824 (2013).
S. Morel, E. Terreno, E. Ugazio, et al., Eur. J. Pharm. Biopharm., 45, 157 – 163 (1998).
S. Bose and B. Michniak-Kohn, Eur. J. Pharm. Sci., 48(3), 442 – 452 (2013).
K. Manjunath, J. S. Reddy, and V. Venkateswarlu, Methods Find. Exp. Clin. Pharmacol., 27(2), 127 – 144 (2005).
V. Jenning and S. Gohla, Int. J. Pharm., 196, 219 – 222 (2000).
B. Siekmann and K. Westesen, Pharm. Pharmacol. Lett., 3, 194 – 197 (1994).
J. Kreuter, V. E. Petrov, D. A. Kharkevich, et al., J. Control. Release, 49(1), 81 – 87 (1997).
V. K. Venishetty, C. Durairaj, R. Sistla, et al., Int. J. Pharm., 335, 167 – 175 (2007).
M. Trotta, F. Debernardi, and O. Caputo, Int. J. Pharm., 257(1), 153 – 160 (2003).
R. Cavalli, O. Caputo, E. Marengo, et al., Pharmazie, 53(6), 392 – 396 (1998).
K. Westesen and B. Siekmann, Int. J. Pharm., 151(1), 35 – 45 (1997).
K. A. Shah, A. A. Date, M. D. Joshi, et al., Int. J. Pharm., 345(1), 163 – 171 (2007).
R. H. Müller and S. A. Runge, in: Submicron Emulsions in Drug Targeting and Delivery, S. Benita (ed.), Harwood Academic, Amsterdam (1998), pp. 219 – 234.
R. H. Müller, W. Mehnert, J. S. Lucks, et al., Eur. J. Pharm. Biopharm., 41 (1): 62 – 69 (1995).
A. Zur Mühlen and W. Mehnert, Pharmazie, 53(8), 552 – 555 (1998).
A. Zur Mühlen, E. Zur Mühlen, H. Niehus, et al., Pharmaceutical Research, 13(9), 1411 – 1416 (1996).
S. Jahnke, in: Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs, R. H. Müller, S. Benita, and B. H. L. Böhm (eds.), Medpharm Scientific Publishers, Stuttgart, (1998), pp. 177 – 200.
M. Üner, Pharmazie, 61(5), 375 – 386 (2006).
R. Lander, W. Manger, M. Scouloudis, et al., Biotechnol. Prog., 16(1), 80 – 85 (2000).
H. Bunjes, B. Siekmann, and K. Westesen, in: Submicron Emulsions in Drug Targeting and Delivery, S. Benita (ed.), Harwood Academic, Amsterdam (1998), pp. 175 – 204.
Eur. Patent No. 0167825 (1990).
United States Patent No. 188837(1993).
S. A. Wissing, O. Kayser, and R. H. Müller, Adv. Drug Deliv. Rev., 56(9), 1257 – 1272 (2004).
B. Sjöström and B. Bergenståhl, Int. J. Pharm., 88(1), 53 – 62 (1992).
B. Siekmann and K. Westesen, Eur. J. Pharm. Biopharm., 42(2), 104 – 109 (1996).
United States Patent No. 5250236 (1993).
M. R. Gasco, Pharm. Tech. Eur., 9, 52 – 58 (1997).
L. Boltri, T. Canal, P. A. Esposito, et al., Proct. Int. Symp. Control. Release Bioact. Mater., 20, 346 – 347 (1993).
A. De Labouret, O. Thioune, H. Fessi, et al., Drug Dev. Ind. Pharm., 21(2), 229 – 241 (1995).
M. R. Gasco, S. Morel, and R. Carpignano, Eur. J. Pharm. Biopharm., 38(1), 7 – 10 (1992).
R. Cavalli, E. Marengo, L. Rodriguez, et al., Eur. J. Pharm. Biopharm., 42(2), 110 – 115 (1996).
R. Cavalli, E. Peira, O. Caputo, et al., Int. J. Pharm., 182(1), 59 – 69 (1999).
M. Igartua, P. Saulnier, B. Heurtault, et al., Int. J. Pharm., 233(1), 149 – 157 (2002).
Y. J. Chen, R. X. Jin, Y. Q. Zhou, et al., Zhongguo Zhong Yao Za Zhi, 31(5), 376 – 379 (2006).
C. S. Kaiser, H. Römpp, and P. C. Schmidt, Pharmazie, 56(12), 907 – 926 (2001).
P. M. Gosselin, R. Thibert, M. Preda, et al., Int. J. Pharm., 252(1 – 2), 225 – 233 (2003).
C. Freitas and R. H. Müller, Eur. J. Pharm. Biopharm., 46(2), 145 – 151. (1998).
M. Nabi-Meibodi, A. Vatanara, A. R. Najafabadi, et al., Colloids Surf. B Biointerfaces, 112, 408 – 414 (2013).
S. Singh, A. K. Dobhal, A. Jain, et al., Chem. Pharm. Bull., 58(5), 650 – 655 (2010).
M. Garcýa-Fuentes, D. Torres, and M. J. Alonso, Colloids Surf. B Biointerfaces, 27(2 – 3), 159 – 168 (2003).
R. Nair, K. S. Arun Kumar, K. Vishnu Priya, et al., J. Biomed. Sci. Res., 3(2), 3683 – 3684 (2011).
C. Charcosset, A. El-Harati, and H. Fessi, J. Control. Release, 108(1), 112 – 120 (2005).
R. M. Shah, D. S. Eldridge, E. A. Palombo, et al., Eur. J. Pharm. Biopharm., 117, 141 – 150 (2017).
C. Pardeshi, P. Rajput, V. Belgamvar, et al., Acta Pharm., 62, 433 – 472 (2012).
K. Sato, in: Crystallization and Polymorphism of Fats and Fatty Acids, N. Garti and K. Sato (eds.), Basel, New York (1988), pp 227 – 266.
T. M. Riddick, Zeta-Meter Manual, Zeta Meter Inc, New York (1968).
C. Freitas and R. H. Müller, Int. J. Pharm., 168(2), 221 – 229 (1998).
E. Meyer, H. Heinzelmann, in: Scanning Tunneling Microscopy. Part II: Surface Science, R. Wiesendanger and H. J. Guntherodt (eds.), Springer Verlag, New York (1992), pp 99 – 149.
S. Chakraborty, B. Sahoo, I. Teraoka, et al, Carbohydr. Polym., 60(4), 475 – 481 (2005).
L. Dulog and T. Schauer, Prog. Org. coat., 28(1), 25 – 31 (1996).
A. S. Dukhin, P. J. Goetz, X. Fang, et al., J. Colloid Inter. Sci., 342(1), 18 – 25 (2010).
V. Jenning, K. Mäder, S. H. Gohla, Int. J. Pharm., 205(1 – 2), 15 – 21 (2000).
A. Dubes, H. Parrot-Lopez, W. Abdelwahed, et al., Eur. J. Pharm. Biopharm., 55(3), 279 – 282 (2003).
B. Drake, C. B. Prater, A. L. Weisenhorn, et al., Science, 243(4898), 1586 – 1589 (1989).
B. G. Zanetti-Ramos, M. B. Fritzen-Garcia, C. S. de Oliveira, et al., Mater Sci. Eng. C, 29(2) 638 – 640 (2009).
O. Robach, C. Quiros, S. M. Valvidares, et al., J. Magn. Magn. Mater, 264(2), 202 – 208 (2003).
V. Jenning and S. H. Gohla, J. Microencapsul., 18(2), 149 – 158 (2001).
P. Pathak and M. Nagarsenker, AAPS. PharmSciTech, 10(3), 985 – 992 (2009).
B. Parmar, S. Mandal, K. C. Petkar, et al., Int. J. Pharm. Sci. Nanotechnol., 4 1483 – 1490 (2011).
Y. Luo, D. Chen, L. Ren, et al., J. Control. Release, 114(1), 53 – 59 (2006).
V. Venkateswarlu and K. Manjunath, J. Control. Release, 95(3), 627 – 638 (2004).
R. H. Müller, C. Schwarz, A. Zur Mühlen, et al., Proct. Int. Symp. Control. Rel. Bioact. Mater., 21, 146 – 147 (1994).
S. Khan, World J. Pharm. Pharm. Sci., 1(1), 96 – 115 (2012).
K. Ruckmani, M Sivakumar, and P. A. Ganeshkumar, J. Nanosci. Nanotechnol., 6(9 – 10), 2991 – 2995 (2006).
S. C. Yang, L. F. Lu, Y. Cai, et al., J. Control. Release, 59(3), 299 – 307 (1999).
R. Pandey, S. Sharma, and G. K. Khuller, Tuberculosis, 85(5), 415 – 420 (2005).
R. Shirodkar, N. Reddy, N. Kumar, et al., Lat. Am. J. Pharm., 34(8), 1526 – 1533 (2015).
S. Martins, I. Tho, I. Reimold, et al., Int. J. Pharm., 439(1), 49 – 62 (2012).
Q. Y. Xiang, M. T. Wang, F. Chen, et al., Arch. Pharm. Res., 30(4), 519 – 525 (2007).
H. Chen, X. Chang, D. Du, et al., J. Control. Release, 110(2), 296 – 306 (2006).
S. K. Jain, M. K. Chourasia, R. Masuriha, et al., Drug Deliv., 12(4), 207 – 215 (2005).
S. Patel, S. Chavhan, H. Soni, et al., J. Drug Target, 19(6), 468 – 474 (2011).
M. A. Kalam, Y. Sultana, A. Ali, et al., J. Biomed. Mater. Res. A, 101(6), 1828 – 1836 (2013).
G. Abdelbary and R. H. Fahmy, AAPS. PharmSciTech, 10(1), 211 – 219 (2009).
J. Liu, T. Gong, H. Fu, et al., Int. J. Pharm., 356(1), 333 – 344 (2008).
M. Radtke and R. H. Müller, New Drugs, 2, 48 – 52 (2001).
M. Radtke, E. B. Souto, and R. H. Müller, Pharm. Tech. Europe, 17(4), 45 – 50 (2005).
R. Shirodkar, C. Misra, G. H. Chethan, et al., Sci. World J., 2015, 12 (2015).
M. Elmowafy, K. Shalaby,M. M. Badran, et al., J. Drug Deliv. Sci. Technol., 45, 230 – 239 (2018).
S. J. Park, C. V. Garcia, G. H. Shin, et al., Food Chem., 225, 213 – 219 (2017).
N. V. Shah, A. K. Seth, and R. Balaraman, et al., J. Adv. Res., 7(3), 423 – 434 (2016).
C. Tetyczka, M. Griesbacher, M. Absenger-Novak, et al., Int. J. Pharm., 526(1 – 2), 188 – 198 (2017).
P. Prabhu, S. Suryavanshi, S. Pathak, et al., Int. J. Pharm., 513(1 – 2), 504 – 517 (2016).
J. C. Schwarz, N. Baisaeng, M. Hoppel, et al., Int. J. Pharm., 447(1 – 2), 213 – 217 (2013).
E. B. Souto, S. A. Wissing, C. M. Barbosa, et al., Int. J. Pharm., 278(1), 71 – 77 (2004).
S. Khan, S. Baboota, J. Ali, et al., Drug Dev. Ind. Pharm., 42(2), 209 – 220 (2016).
V. M. Ghate, S. A. Lewis, P. Prabhu, et al., Eur. J. Pharm. Biopharm., 108, 253 – 261 (2016).
S. Alam, M. Aslam, A. Khan, et al., Drug Deliv., 23(2), 601 – 609 (2016).
Ü. Gönüllü, M. Üner, G. Yener, et al., Acta Pharm., 65(1), 1 – 13 (2015).
R. G. Madane and H. S. Mahajan, Drug Deliv., 23(4), 1326 – 1334 (2016).
A. Patil-Gadhe, A. Kyadarkunte., M. Patole, et al., Eur. J. Pharm. Biopharm., 88(1), 169 – 177 (2014).
S. P. Balguri, G. R. Adelli, and S. Majumdar, Eur. J. Pharm. Biopharm., 109, 224 – 235 (2016).
C. Zhang, S. Luo, Z. Zhang, et al., J. Taiwan Inst. Chem. Eng., 71, 338 – 343 (2017).
T. B. Devkar, A. R. Tekade, and K. R. Khandelwal, Colloids Surf. B, 122, 143 – 150 (2014).
E. B. Souto and R. H. Müller, J. Microencapul., 22(5), 501 – 510 (2005).
N. P. Aditya, A. S. Macedo, S. Doktorovova, et al., LWT-Food Sci. Technol., 59(1), 115 – 121 (2014).
A. Costa, B. Sarmento, and V. Seabra, Eur. J. Pharm. Sci., 114, 103 – 113 (2018).
A. Vyas, A. Jain, P. Hurkat, et al., Colloids Surf. B Biointerfaces, 131, 155 – 161 (2015).
J. K. Wang, Y. Y. Zhou, S. J. Guo, et al., Mater. Sci. Eng. C., 76, 944 – 950 (2017).
R. Swami, I. Singh, M. K. Jeengar, et al., Int. J. Pharm., 486(1–2), 287 – 296 (2015).
M. Ferreira, L. Barreiros, M. A. Segundo, et al., Colloids Surf. B Biointerfaces, 159, 23 – 29 (2017).
X. Y. Yang, Y. X. Li, M. Li, et al., Cancer Lett., 334(2), 338 – 345(2013).
S. K. Singh, M. K. Hidau, S. Gautam, et al., Int. J. Biol. Macromol., 108, 1092 – 1100 (2018).
L. M. Negi, M. Jaggi, V. Joshi, et al., Int. J. Biol. Macromol., 72, 569 – 574(2015).
C. Zhao, T. Fan, Y. Yang, et al., Int. J. Pharm., 450(1 – 2), 11 – 20 (2013).
F. Meng, S. Asghar, Y. Xu, et al., Int. J. Pharm., 506(1 – 2),46 – 56 (2016).
Acknowledgements
Authors are thankful to All-India Council for Technical Education, New Delhi, for financial support. Authors are grateful to Manipal Academy of Higher Education, Manipal, for providing necessary facilities.
Conflict of Interest
Authors hereby declare that, they do not have any conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shirodkar, R.K., Kumar, L., Mutalik, S. et al. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Emerging Lipid Based Drug Delivery Systems. Pharm Chem J 53, 440–453 (2019). https://doi.org/10.1007/s11094-019-02017-9
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-019-02017-9