Lipoidal-Nano Architecture for Parental Drug Delivery: Formulation Development and Regulatory Concerns

Vikas       Jhawat; Anil    Kumar    Sharma; Vandana       Garg; Monika      Gulia; Rohit       Dutt
Abstract

The nanoparticles as drug carriers have demonstrated enhanced targeting, and sustained/- controlled drug release, as evident from numerous investigations that have shown promising outcomes facilitating the wellbeing of humans in the desired manner. The lipid-based nanoparticles are biodegradable and considered biocompatible by virtue of being composed of lipid moieties mimicking physiological lipids of biological systems which is their prime advantage over the other polymeric systems. A variety of such lipid carriers have been reported to be delivered from the parenteral route. However, there are certain pitfalls which are associated with lipid nanoparticles such as toxicity, poor scale up potential, immunological reactions and absence of straight forward regulatory guidelines that address the issues of lipoidal nanocarriers such as their classification, approval and compliance of governmental policies. Therefore attention must be given to address the technological and regulatory challenges associated with lipoidal nano-formulations for parenteral administration to smoothen the approval process throughout the world and bringing the same to the terminal users on time.
Keywords: Lipids carriers, nanotechnology, parenteral route, regulatory challenges, lipid nanoparticulates, lipoidal nanocarriers.
Graphical Abstract

[1] 
Ahire E, Thakkar S, Darshanwad M, Misra M. Parenteral nanosuspensions: A brief review from solubility enhancement to more novel and specific applications. Acta Pharm Sin B  2018; 8(5): 733-55.
[http://dx.doi.org/10.1016/j.apsb.2018.07.011] [PMID: 30245962] 
[2] 
Verma S, Burgess D. Solid nanosuspensions: The emerging technology and pharmaceutical applications as nanomedicine.Pharmaceutical suspensions.  New York: Springer 2009; pp. 285-318.
[3] 
Lu Y, Li Y, Wu W. Injected nanocrystals for targeted drug delivery. Acta Pharm Sin B  2016; 6(2): 106-13.
[http://dx.doi.org/10.1016/j.apsb.2015.11.005] [PMID: 27006893] 
[4] 
Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm  2010; 399(1-2): 129-39.
[http://dx.doi.org/10.1016/j.ijpharm.2010.07.044] [PMID: 20674732] 
[5] 
Nguyen KC, Willmore WG, Tayabali AF. Cadmium telluride quantum dots cause oxidative stress leading to extrinsic and intrinsic apoptosis in hepatocellular carcinoma HepG2 cells. Toxicology  2013; 306: 114-23.
[http://dx.doi.org/10.1016/j.tox.2013.02.010] [PMID: 23485651] 
[6] 
Schmid G, Decker M, Ernst H, et al. Small dimensions and material properties A definition of nanotechnology.  Europäische Akademie 2003; pp. 1-135.
[7] 
Stylios GK, Giannoudis PV, Wan T. Applications of nanotechnologies in medical practice. Injury  2005; 36(Suppl. 4): S6-S13.
[http://dx.doi.org/10.1016/j.injury.2005.10.011] [PMID: 16291325] 
[8] 
Yokoyama M. Drug targeting with nano-sized carrier systems. J Artif Organs  2005; 8(2): 77-84.
[http://dx.doi.org/10.1007/s10047-005-0285-0] [PMID: 16094510] 
[9] 
Suri SS, Fenniri H, Singh B. Nanotechnology-based drug delivery systems. J Occup Med Toxicol  2007; 2: 16.
[http://dx.doi.org/10.1186/1745-6673-2-16] [PMID: 18053152] 
[10] 
De Jong WH, Borm PJA. Drug delivery and nanoparticles: Applications and hazards. Int J Nanomedicine  2008; 3(2): 133-49.
[http://dx.doi.org/10.2147/IJN.S596] [PMID: 18686775] 
[11] 
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnology  2018; 16(1): 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877] 
[12] 
Surenya RS, Nair SKV, Kumar LV. Pharmaceutical nano drug delivery route administration for cancer therapy. Adv Sci Eng Med  2015; 7: 739-45.
[http://dx.doi.org/10.1166/asem.2015.1767] 
[13] 
Verma P, Thakur AS, Deshmukh K, Jha AK, Verma S. Routes of drug administration. Int J Pharm Stud Res  2010; 1: 54-9.
[14] 
Barenholz Y. Doxil®--the first FDA-approved nano-drug: lessons learned. J Control Release  2012; 160(2): 117-34.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.020] [PMID: 22484195] 
[15] 
Jawahar N, Meyyanathan SN. Polymeric nanoparticles for drug delivery and targeting: A comprehensive review. Int J Health Allied Sci  2012; 1: 217-23.
[http://dx.doi.org/10.4103/2278-344X.107832] 
[16] 
Mehnert W, Mäder K. Solid lipid nanoparticles: Production, characterization and applications. Adv Drug Deliv Rev  2001; 47(2-3): 165-96.
[http://dx.doi.org/10.1016/S0169-409X(01)00105-3] [PMID: 11311991] 
[17] 
Braddock M. Nanomedicines: Design, delivery and detection. Cambridge: Royal Society of Chemistry 2016.
[http://dx.doi.org/10.1039/9781782622536] 
[18] 
Tian X, Li H, Zhang D, et al. Nanosuspension for parenteral delivery of a p-terphenyl derivative: Preparation, characteristics and pharmacokinetic studies. Colloids Surf B Biointerfaces  2013; 108: 29-33.
[http://dx.doi.org/10.1016/j.colsurfb.2013.02.038] [PMID: 23528604] 
[19] 
Panayiotis PC, Mahesh VC, Robert S. Advances in lipid nanodispersions for parenteral drug delivery and targetting. Science  2008; 60: 757-67.
[20] 
Joshi MD, Müller RH. Lipid nanoparticles for parenteral delivery of actives. Eur J Pharm Biopharm  2009; 71(2): 161-72.
[http://dx.doi.org/10.1016/j.ejpb.2008.09.003] [PMID: 18824097] 
[21] 
Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm  2000; 50(1): 161-77.
[http://dx.doi.org/10.1016/S0939-6411(00)00087-4] [PMID: 10840199] 
[22] 
Wissing SA, Kayser O, Müller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev  2004; 56(9): 1257-72.
[http://dx.doi.org/10.1016/j.addr.2003.12.002] [PMID: 15109768] 
[23] 
Anton N, Benoit JP, Saulnier P. Design and production of nanoparticles formulated from nano-emulsion templates-a review. J Control Release  2008; 128(3): 185-99.
[http://dx.doi.org/10.1016/j.jconrel.2008.02.007] [PMID: 18374443] 
[24] 
Rossi J. Principles in the development of intravenous lipid emulsions.Role of lipid excipients in modifying oral and parenteral drug delivery.  Hoboken, New Jersey: Wiley-Interscience 2007; pp. 88-123.
[25] 
Wang Z, Li Z, Zhang D, Miao L, Huang G. Development of etoposide-loaded bovine serum albumin nanosuspensions for parenteral delivery. Drug Deliv  2015; 22(1): 79-85.
[http://dx.doi.org/10.3109/10717544.2013.871600] [PMID: 24401038] 
[26] 
Doijad RC, Manvi FV, Swati S, Rony MS. Niosomal drug delivery of Cisplatin: Development and characterization. Indian Drugs  2008; 45: 713-8.
[27] 
Mamot C, Drummond DC, Hong K, Kirpotin DB, Park JW. Liposome-based approaches to overcome anticancer drug resistance. Drug Resist Updat  2003; 6(5): 271-9.
[http://dx.doi.org/10.1016/S1368-7646(03)00082-7] [PMID: 14643297] 
[28] 
Marchiori ML, Lubini G, Dalla Nora G, et al. Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: Preparation, characterization, and
                        in vitro
                        drug release study.
                     Drug Dev Ind Pharm  2010; 36(8): 962-71.
[http://dx.doi.org/10.3109/03639041003598960] [PMID: 20590450] 
[29] 
Bae Y, Kataoka K. Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers. Adv Drug Deliv Rev  2009; 61(10): 768-84.
[http://dx.doi.org/10.1016/j.addr.2009.04.016] [PMID: 19422866] 
[30] 
Tyrrell ZL, Shen YQ, Radosz M. Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Prog Polym Sci  2010; 35: 1128-43.
[http://dx.doi.org/10.1016/j.progpolymsci.2010.06.003] 
[31] 
Radtke M, Muller RH. Novel concept of topical cyclosporine delivery with supersaturated SLN creams. Int Symp Control Rel Bioact Mater  2001; 28: 470-1.
[32] 
Cavalli R, Caputo O, Gasco MR. Solid lipospheres of doxorubicin and idarubicin. Int J Pharm  1993; 89: R9-R12.
[http://dx.doi.org/10.1016/0378-5173(93)90313-5] 
[33] 
zur Muhlen A, Mehnert W. Drug release and release mechanism of prednisolone loaded solid lipid nanoparticles. Pharmazie  1998; 53: 552-5.
[34] 
Zhang L, Pornpattananangku D, Hu CMJ, Huang CM. Development of nanoparticles for antimicrobial drug delivery. Curr Med Chem  2010; 17(6): 585-94.
[http://dx.doi.org/10.2174/092986710790416290] [PMID: 20015030] 
[35] 
Shah P, Bhalodia D, Shelat P. Nanoemulsion: A pharmaceutical review. Syst Rev Pharm  2010; 1: 24-32.
[http://dx.doi.org/10.4103/0975-8453.59509] 
[36] 
McClements DJ. Colloidal bases of emulsion colour. Curr Opin Colloid In Sci  2002; 7: 451-5.
[http://dx.doi.org/10.1016/S1359-0294(02)00075-4] 
[37] 
Aboofazeli R. Nanometric-scaled emulsions (nanoemulsions). Iran J Pharm Res  2010; 9(4): 325-6.
[PMID: 24381596] 
[38] 
Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising drug delivery strategy. J Pharm Pharmacol  2004; 56(7): 827-40.
[http://dx.doi.org/10.1211/0022357023691] [PMID: 15233860] 
[39] 
Pu X, Sun J. Moli and Zhonggui He. Formulation of nanosuspension as a new approach for the delivery of poorly soluble drugs. Curr Nanosci  2009; 5: 417-27.
[http://dx.doi.org/10.2174/157341309789378177] 
[40] 
Muthu MS, Singh S. Poly (D, L-lactide) nanosuspensions of risperidone for parenteral delivery: Formulation and
                        in-vitro
                        evaluation.
                     Curr Drug Deliv  2009; 6(1): 62-8.
[http://dx.doi.org/10.2174/156720109787048302] [PMID: 19418957] 
[41] 
Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm  1998; 172: 33-70.
[http://dx.doi.org/10.1016/S0378-5173(98)00169-0] 
[42] 
Akhilesh D, Bini KB, Kamath JV. Review on span-60 based non-ionic surfactant vesicles (niosomes) as novel drug delivery. Int J Res Pharm Biomed Sci  2012; 3: 6-12.
[43] 
Seleci DA, Seleci M, Walter JG, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: Fundamentals and recent applications. J Nanomater  2016; 7372306: 1-13.
[http://dx.doi.org/10.1155/2016/7372306] 
[44] 
Fang JY, Hong CT, Chiu WT, Wang YY. Effect of liposomes and niosomes on skin permeation of enoxacin. Int J Pharm  2001; 219(1-2): 61-72.
[http://dx.doi.org/10.1016/S0378-5173(01)00627-5] [PMID: 11337166] 
[45] 
Carafa M, Marianecci C, Di Marzio L, et al. Potential dopamine prodrug-loaded liposomes: Preparation, characterization, and
                        in vitro
                        stability studies.
                     J Liposome Res  2010; 20(3): 250-7.
[http://dx.doi.org/10.3109/08982100903384129] [PMID: 19958070] 
[46] 
Sharma A, Sharma US. Liposomes in drug delivery: Progress and limitations. Int J Pharm  1997; 154: 123-40.
[http://dx.doi.org/10.1016/S0378-5173(97)00135-X] 
[47] 
Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems: A review. Pharm Acta Helv  1995; 70(2): 95-111.
[http://dx.doi.org/10.1016/0031-6865(95)00010-7] [PMID: 7651973] 
[48] 
Zhang L, Granick S. How to stabilize phospholipid liposomes (using nanoparticles). Nano Lett  2006; 6(4): 694-8.
[http://dx.doi.org/10.1021/nl052455y] [PMID: 16608266] 
[49] 
Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin: Permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst  1996; 13(3-4): 257-388.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v13.i3-4.30] [PMID: 9016383] 
[50] 
Minkov I, Ivanova T, Panaiotov I, Proust J, Saulnier P. Reorganization of lipid nanocapsules at air-water interface: Part 2. Properties of the formed surface film. Colloids Surf B Biointerfaces  2005; 44(4): 197-203.
[http://dx.doi.org/10.1016/j.colsurfb.2005.07.001] [PMID: 16081256] 
[51] 
Vonarbourg A, Saulnier P, Passirani C, Benoit JP. Electrokinetic properties of noncharged lipid nanocapsules: Influence of the dipolar distribution at the interface. Electrophoresis  2005; 26(11): 2066-75.
[http://dx.doi.org/10.1002/elps.200410145] [PMID: 15852355] 
[52] 
Huynh NT, Passirani C, Saulnier P, Benoit JP. Lipid nanocapsules: A new platform for nanomedicine. Int J Pharm  2009; 379(2): 201-9.
[http://dx.doi.org/10.1016/j.ijpharm.2009.04.026] [PMID: 19409468] 
[53] 
Hoarau D, Delmas P, David S, Roux E, Leroux JC. Novel long-circulating lipid nanocapsules. Pharm Res  2004; 21(10): 1783-9.
[http://dx.doi.org/10.1023/B:PHAM.0000045229.87844.21] [PMID: 15553223] 
[54] 
Fachinetto JM, Ourique AF, Lubini G, Tedesco SB, Silva ACF, Beck RCR. Tretinoin-loaded polymeric nanocapsules: Evaluation of the potential to improve the antiproliferative activities on Allium cepa root-tip compared to the free drug. Lat Am J Pharm  2008; 27: 668-73.
[55] 
Fontana MC, Coradini K, Guterres SS, Pohlmann AR, Beck RCR. Nanoencapsulation as a way to control the release and to increase the photostability of clobetasol propionate: Influence of the nanostructured system. J Biomed Nanotechnol  2009; 5(3): 254-63.
[http://dx.doi.org/10.1166/jbn.2009.1030] [PMID: 20055007] 
[56] 
Constantinides PP, Chaubal MV, Shorr R. Advances in lipid nanodispersions for parenteral drug delivery and targeting. Adv Drug Deliv Rev  2008; 60(6): 757-67.
[http://dx.doi.org/10.1016/j.addr.2007.10.013] [PMID: 18096269] 
[57] 
Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett  1990; 268(1): 235-7.
[http://dx.doi.org/10.1016/0014-5793(90)81016-H] [PMID: 2384160] 
[58] 
Trubetskoy VS, Torchilin VP. Use of polyoxyethylene-lipid conjugates as long-circulating carriers for delivery of therapeutic and diagnostic agents. Adv Drug Deliv Rev  1995; 16: 311-20.
[http://dx.doi.org/10.1016/0169-409X(95)00032-3] 
[59] 
Lasic DD, Woodle MC, Martin FJ, Valentincic T. Phase behavior of ‘stealth-lipid’ decithin mixtures. Period Biol  1991; 93: 287-90.
[60] 
Lasic DD. Mixed micelles in drug delivery. Nature  1992; 355(6357): 279-80.
[http://dx.doi.org/10.1038/355279a0] [PMID: 1731228] 
[61] 
Hwang SR, Lim SJ, Park JS, Kim CK. Phospholipid-based microemulsion formulation of all-trans-retinoic acid for parenteral administration. Int J Pharm  2004; 276(1-2): 175-83.
[http://dx.doi.org/10.1016/j.ijpharm.2004.02.025] [PMID: 15113624] 
[62] 
Müller RH, Radtke M, Wissing SA. Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm  2002; 242(1-2): 121-8.
[http://dx.doi.org/10.1016/S0378-5173(02)00180-1] [PMID: 12176234] 
[63] 
Radtke M, Muller RH. NLC-nanostructured lipid carriers: The new generation of lipid drug carriers. New Drugs  2001; 2: 97-138.
[64] 
Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm  2009; 366(1-2): 170-84.
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.003] [PMID: 18992314] 
[65] 
Shidhaye SS, Vaidya R, Sutar S, Patwardhan A, Kadam VJ. Solid lipid nanoparticles and nanostructured lipid carriers innovative generations of solid lipid carriers. Curr Drug Deliv  2008; 5(4): 324-31.
[http://dx.doi.org/10.2174/156720108785915087] [PMID: 18855604] 
[66] 
Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev  2002; 54(Suppl. 1): S131-55. b
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720] 
[67] 
Teeranachaideekul V, Müller RH, Junyaprasert VB. Encapsulation of ascorbyl palmitate in nanostructured lipid carriers (NLC) effects of formulation parameters on physicochemical stability. Int J Pharm  2007; 340(1-2): 198-206.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.022] [PMID: 17482778] 
[68] 
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] 
[69] 
Solaro R, Chiellini F, Battisti A. Targeted delivery of protein drugs by nanocarriers. Materials (Basel)  2010; 3: 1928-80.
[http://dx.doi.org/10.3390/ma3031928] 
[70] 
Din FU, Aman W, Ullah I, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine  2017; 12: 7291-309.
[http://dx.doi.org/10.2147/IJN.S146315] [PMID: 29042776] 
[71] 
Li J, Wang X, Zhang T, et al. A review on phospholipids and their main applications in drug delivery systems. Asian J Pharm Sci  2015; 10: 81-98.
[http://dx.doi.org/10.1016/j.ajps.2014.09.004] 
[72] 
Gabizon AA. Applications of liposomal drug delivery systems to cancer therapy.Nanotechnology for cancer therapy.  Boca Raton: CRC Press 2007; pp. 595-611.
[73] 
Kaur CD, Nahar M, Jain NK. Lymphatic targeting of zidovudine using surface-engineered liposomes. J Drug Target  2008; 16(10): 798-805.
[http://dx.doi.org/10.1080/10611860802475688] [PMID: 19005941] 
[74] 
Hu FQ, Yuan H, Zhang HH, Fang M. Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm  2002; 239(1-2): 121-8.
[http://dx.doi.org/10.1016/S0378-5173(02)00081-9] [PMID: 12052697] 
[75] 
Westesen K, Bunjes H, Koch MHJ. Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. J Control Release  1997; 48: 223-36.
[http://dx.doi.org/10.1016/S0168-3659(97)00046-1] 
[76] 
Kim JK, Park JS, Kim CK. Development of a binary lipid nanoparticles formulation of itraconazole for parenteral administration and controlled release. Int J Pharm  2010; 383(1-2): 209-15.
[http://dx.doi.org/10.1016/j.ijpharm.2009.09.008] [PMID: 19747966] 
[77] 
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] 
[78] 
Jia L, Zhang D, Li Z, et al. Nanostructured lipid carriers for parenteral delivery of silybin: Biodistribution and pharmacokinetic studies. Colloids Surf B Biointerfaces  2010; 80(2): 213-8.
[http://dx.doi.org/10.1016/j.colsurfb.2010.06.008] [PMID: 20621458] 
[79] 
Liu D, Liu Z, Wang L, Zhang C, Zhang N. Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids Surf B Biointerfaces  2011; 85(2): 262-9.
[http://dx.doi.org/10.1016/j.colsurfb.2011.02.038] [PMID: 21435845] 
[80] 
Constantinides PP, Lambert KJ, Tustian AK, et al. Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel. Pharm Res  2000; 17(2): 175-82.
[http://dx.doi.org/10.1023/A:1007565230130] [PMID: 10751032] 
[81] 
Araújo FA, Kelmann RG, Araújo BV, Finatto RB, Teixeira HF, Koester LS. Development and characterization of parenteral nanoemulsions containing thalidomide. Eur J Pharm Sci  2011; 42(3): 238-45.
[http://dx.doi.org/10.1016/j.ejps.2010.11.014] [PMID: 21130164] 
[82] 
Wang T, Feng L, Yang S, Liu Y, Zhang N. Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency. Drug Deliv  2017; 24(1): 800-10.
[http://dx.doi.org/10.1080/10717544.2016.1225853] [PMID: 28502199] 
[83] 
Wang L, Li M, Zhang N. Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy. Int J Nanomedicine  2012; 7: 3281-94.
[PMID: 22802688] 
[84] 
Ruckmani K, Sankar V, Sivakumar M. Tissue distribution, pharmacokinetics and stability studies of zidovudine delivered by niosomes and proniosomes. J Biomed Nanotechnol  2010; 6(1): 43-51.
[http://dx.doi.org/10.1166/jbn.2010.1101] [PMID: 20499831] 
[85] 
Allard E, Passirani C, Garcion E, et al. Lipid nanocapsules loaded with an organometallic tamoxifen derivative as a novel drug-carrier system for experimental malignant gliomas. J Control Release  2008; 130(2): 146-53.
[http://dx.doi.org/10.1016/j.jconrel.2008.05.027] [PMID: 18582507] 
[86] 
Ourique AF, Azoubel S, Ferreira CV, et al. Lipid-core nanocapsules as a nanomedicine for parenteral administration of tretinoin: Development and
                        in vitro
                        antitumor activity on human myeloid leukaemia cells.
                     J Biomed Nanotechnol  2010; 6(3): 214-23.
[http://dx.doi.org/10.1166/jbn.2010.1120] [PMID: 21179938] 
[87] 
Khalid MN, Simard P, Hoarau D, Dragomir A, Leroux JC. Long circulating poly(ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors. Pharm Res  2006; 23(4): 752-8.
[http://dx.doi.org/10.1007/s11095-006-9662-5] [PMID: 16550475] 
[88] 
Alkan-Onyuksel H, Ramakrishnan S, Chai HB, Pezzuto JM. A mixed micellar formulation suitable for the parenteral administration of taxol. Pharm Res  1994; 11(2): 206-12.
[http://dx.doi.org/10.1023/A:1018943021705] [PMID: 7909371] 
[89] 
Hjelm RP, Thiyagarajan P, Onyuksel HA. Organization of phosphatidycholine and bile salt in rodlike mixed micelles. J Phys Chem  1992; 96: 8653-61.
[http://dx.doi.org/10.1021/j100200a080] 
[90] 
Sahoo BK, Pattajoshi SP. Challenges of nano drug delivery and its safety issues. Int J Pharm and Pharm Res  2016; 6: 523-31.
[91] 
Winter E, Pizzol CD, Locatelli C, Crezkynski-Pasa TB. Development and evaluation of lipid nanoparticles for drug delivery: Study of toxicity 
                        in vitro
                        and
                        in vivo
                        .
                     J Nanosci Nanotechnol  2015; 15: 1-10.
[PMID: 27433582] 
[92] 
Powers KW, Brown SC, Krishna VB, Wasdo SC, Moudgil BM, Roberts SM. Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol Sci  2006; 90(2): 296-303.
[http://dx.doi.org/10.1093/toxsci/kfj099] [PMID: 16407094] 
[93] 
Oberdoster G. Safety assessment for nanotechnology and nanomedicine: Concept of nanotoxicology. J Intern Med  2009; 267: 89-105.
[http://dx.doi.org/10.1111/j.1365-2796.2009.02187.x] 
[94] 
Sharma A, Madhunapantula SV, Robertson GP. Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems. Expert Opin Drug Metab Toxicol  2012; 8(1): 47-69.
[http://dx.doi.org/10.1517/17425255.2012.637916] [PMID: 22097965] 
[95] 
Dhawan A, Sharma V. Toxicity assessment of nanomaterials: Methods and challenges. Anal Bioanal Chem  2010; 398(2): 589-605.
[http://dx.doi.org/10.1007/s00216-010-3996-x] [PMID: 20652549] 
[96] 
Yang Y, Qin Z, Zeng W, et al. Toxicity assessment of nanoparticles in various systems and organs. Nanotechnol Rev  2017; 6: 279-89.
[http://dx.doi.org/10.1515/ntrev-2016-0047] 
[97] 
Puri A, Loomis K, Smith B, et al. Lipid-based nanoparticles as pharmaceutical drug carriers: From concepts to clinic. Crit Rev Ther Drug Carrier Syst  2009; 26(6): 523-80.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i6.10] [PMID: 20402623] 
[98] 
Miller CR, Bondurant B, McLean SD, McGovern KA, O’Brien DF. Liposome-cell interactions
                         in vitro
                        : Effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes.
                     Biochemistry  1998; 37(37): 12875-83.
[http://dx.doi.org/10.1021/bi980096y] [PMID: 9737866] 
[99] 
Thanos C, Sandor M, Jong Y, et al. Inter-species uptake of polymeric particles. Proc MRS  1999; 550: 65-70.
[http://dx.doi.org/10.1557/PROC-550-65] 
[100] 
Galindo-Rodríguez SA, Puel F, Briançon S, Allémann E, Doelker E, Fessi H. Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles. Eur J Pharm Sci  2005; 25(4-5): 357-67.
[http://dx.doi.org/10.1016/j.ejps.2005.03.013] [PMID: 15916889] 
[101] 
Colombo AP, Briançon S, Lieto J, Fessi H. Project, design, and use of a pilot plant for nanocapsule production. Drug Dev Ind Pharm  2001; 27(10): 1063-72.
[http://dx.doi.org/10.1081/DDC-100108369] [PMID: 11794809] 
[102] 
Purushotham H. Transfer of nanotechnologies from R&D institutions to SMEs in India.  Tech Monitor 2012; pp. 23-33.
[103] 
Khan MU. Problems of technology transfer from laboratory to industry and policy issues in India. Int J Serv Technol Manag  2000; 1: 375-94.
[http://dx.doi.org/10.1504/IJSTM.2000.001583] 
[104] 
Mazzola L. Commercializing nanotechnology. Nat Biotechnol  2003; 21(10): 1137-43.
[http://dx.doi.org/10.1038/nbt1003-1137] [PMID: 14520392] 
[105] 
McNeil RD, Lowe J, Mastroianni T, Cronin J, Ferk D. Report-Barriers to nanotechnology commercialization. U.S. Department of Commerce Technology Administration 2007.
[106] 
Aithal PS, Aithal S. Nanotechnology innovations and commercialization –opportunities, challenges & reasons for delay.MPRA.   2016; pp. 1-9.
[107] 
Jain S, Edwards M, Spencer L. Advances and challenges in the development of drug delivery systems – A European perspective. Regulatory Rapporteur  2016; 13: 4-8.
[108] 
Medicines and Healthcare products Regulatory Agency (MHRA). Guidance: Decide if your product is a medicine or a medical device. 2019. Available from:https://www.gov.uk/guidance/decide-if-your-product-is-a-medicine-or-a-medical-device
[109] 
Mühlebach S. Regulatory challenges of nanomedicines and their follow-on versions: A generic or similar approach? Adv Drug Deliv Rev  2018; 131: 122-31.
[http://dx.doi.org/10.1016/j.addr.2018.06.024] [PMID: 29966685] 
[110] 
Mühlebach S, Borchard G, Yildiz S. Regulatory challenges and approaches to characterize nanomedicines and their follow-on similars. Nanomedicine (Lond)  2015; 10(4): 659-74.
[http://dx.doi.org/10.2217/nnm.14.189] [PMID: 25723097] 
[111] 
David B Fischer. Nanotechnology - scientific and regulatory challenges, 19 Vill. Envtl LJ 2008. Available from:https://digitalcommons.law.villanova.edu/elj/vol19/iss2/2
Cite As
Current Applied Polymer Science

Lipoidal-Nano Architecture for Parental Drug Delivery: Formulation Development and Regulatory Concerns

Abstract

Graphical Abstract
