Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Lipid Drug Conjugates for Improved Therapeutic Benefits

Author(s): Priya Shrivastava, Laxmikant Gautam, Anamika Jain, Nikhar Vishwakarma, Sonal Vyas and Suresh P. Vyas*

Volume 26 , Issue 27 , 2020

Page: [3187 - 3202] Pages: 16

DOI: 10.2174/1381612826666200311124003

Price: $65

Abstract

Lipid drug conjugates (LDCs) are the chemical entities, which are commonly referred to as lipoidal prodrug. They contain the bioactive molecules, covalently or non-covalently linked with lipids like fatty acids, glycerides or phospholipids. Lipid drug conjugates are fabricated with the aim of increasing drug payload. It also prevents leakage of a highly polar bioactive(s) from the lipophilic matrix. Conjugating lipidic moieties to bioactive molecules improves hydrophobicity. It also modifies other characteristics of bioactive(s). These conjugates possess numerous merits encompassing enhanced tumor targeting, lymphatic system targeting, systemic bioavailability and decreased toxicity. Different conjugation approaches, chemical linkers and spacers can be used to synthesize LDCs based on the chemical behaviour of lipidic moieties and bioactive(s). The factors such as coupling/ conjugation methods, the linkers etc. regulate and control the release of bioactive(s) from the LDCs. It is considered as a crucial parameter for the better execution of the LDCs. The purpose of this review is to explore widely the potential of LDCs as an approach for improving the therapeutic indices of bioactive(s). In this review, the conjugation methods, various lipids used for preparing LDCs, and advantages of using LDCs are summarized. Though LDCs might be administered without using a carrier; however, majority of them are incorporated in an appropriate nanocarrier system. In the conjugates, the lipidic component may considerably improve the loading of lipoidal bioactive(s) in the lipid compartments. This results in high % drug entrapment in nanocarriers with greater stability. Several nanometric carriers such as polymeric nanoparticles, micelles, liposomes, emulsions and lipid nanoparticles, which have been explored, are reviewed here.

Keywords: Lipid-drug conjugates, conjugation, lipids, linkers, prodrug and nanoparticles, liposomes.

[1]
Date T, Paul K, Singh N, Jain S. Drug-Lipid Conjugates for Enhanced Oral Drug Delivery. AAPS PharmSciTech 2019; 20(2): 41.
[http://dx.doi.org/10.1208/s12249-018-1272-0] [PMID: 30610658]
[2]
Adhikari P, Pal P, Das AK, Ray S, Bhattacharjee A, Mazumder B. Nano lipid-drug conjugate: An integrated review. Int J Pharm 2017; 529(1-2): 629-41.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.039] [PMID: 28723407]
[3]
Irby D, Du C, Li F. Lipid-drug conjugate for enhancing drug delivery. Mol Pharm 2017; 14(5): 1325-38.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b01027] [PMID: 28080053]
[4]
Battaglia L, Serpe L, Foglietta F, et al. Application of lipid nanoparticles to ocular drug delivery. Expert Opin Drug Deliv 2016; 13(12): 1743-57.
[http://dx.doi.org/10.1080/17425247.2016.1201059] [PMID: 27291069]
[5]
Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol Rep 2012; 64(5): 1020-37.
[http://dx.doi.org/10.1016/S1734-1140(12)70901-5] [PMID: 23238461]
[6]
Dahan A, Duvdevani R, Shapiro I, Elmann A, Finkelstein E, Hoffman A. The oral absorption of phospholipid prodrugs: in vivo and in vitro mechanistic investigation of trafficking of a lecithin valproic acid conjugate following oral administration. J Control Release 2008; 126(1): 1-9.
[http://dx.doi.org/10.1016/j.jconrel.2007.10.025] [PMID: 18082281]
[7]
Alexander RL, Greene BT, Torti SV, Kucera GL. A novel phospholipid gemcitabine conjugate is able to bypass three drug resistance mechanisms. Cancer Chemother Pharmacol 2005; 56(1): 15-21.
[http://dx.doi.org/10.1007/s00280-004-0949-0] [PMID: 15789226]
[8]
Isoherranen N, Yagen B, Bialer M. New CNS-active drugs which are second-generation valproic acid: can they lead to the development of a magic bullet? Curr Opin Neurol 2003; 16(2): 203-11.
[http://dx.doi.org/10.1097/00019052-200304000-00014] [PMID: 12644750]
[9]
Han S, Quach T, Hu L, et al. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies. J Control Release 2014; 177: 1-10.
[http://dx.doi.org/10.1016/j.jconrel.2013.12.031] [PMID: 24398334]
[10]
Han S, Hu L, Gracia . etal.Lymphatic transport and lymphocyte targeting of a triglyceride mimetic prodrug is enhanced in a large animal model: studies in greyhound dogs. Mol Pharm 2016; 13(10): 3351-61.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00195] [PMID: 27608166]
[11]
Hu L, Quach T, Han S, et al. Glyceride-mimetic prodrugs incorporating self-immolative spacers promote lymphatic transport, avoid first-pass metabolism, and enhance oral bioavailability. Angew Chem Int Ed Engl 2016; 55(44): 13700-5.
[http://dx.doi.org/10.1002/anie.201604207] [PMID: 27482655]
[12]
Vlasenko YV, Alekseeva AS, Vodovozova EL. Synthesis of a fluorescent analogue of methotrexate lipophilic prodrug. Russ J Bioorganic Chem 2014; 40(1): 114-7.
[http://dx.doi.org/10.1134/S1068162014010129]
[13]
Amitay Y, Shmeeda H, Patil Y, et al. Pharmacologic studies of a prodrug of mitomycin C in pegylated liposomes (promitil®): high stability in plasma and rapid thiolytic prodrug activation in tissues. Pharm Res 2016; 33(3): 686-700.
[http://dx.doi.org/10.1007/s11095-015-1819-7] [PMID: 26572644]
[14]
Ansell SM, Johnstone SA, Tardi PG, et al. Modulating the therapeutic activity of nanoparticle delivered paclitaxel by manipulating the hydrophobicity of prodrug conjugates. J Med Chem 2008; 51(11): 3288-96.
[http://dx.doi.org/10.1021/jm800002y] [PMID: 18465845]
[15]
Dichwalkar T, Patel S, Bapat S, et al. Omega-3 fatty acid grafted PAMAM-Paclitaxel conjugate exhibits enhanced anticancer activity in upper gastrointestinal cancer cells. Macromol Biosci 2017; 17(8)1600457
[http://dx.doi.org/10.1002/mabi.201600457] [PMID: 28485094]
[16]
Sun B, Luo C, Cui W, Sun J, He Z. Chemotherapy agent-unsaturated fatty acid prodrugs and prodrug-nanoplatforms for cancer chemotherapy. J Control Release 2017; 264: 145-59.
[http://dx.doi.org/10.1016/j.jconrel.2017.08.034] [PMID: 28844757]
[17]
Stuurman FE, Voest EE, Awada A, et al. Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors. Invest New Drugs 2013; 31(4): 959-66.
[http://dx.doi.org/10.1007/s10637-013-9925-z] [PMID: 23345000]
[18]
Pedersen PJ, Christensen MS, Ruysschaert T, et al. Synthesis and biophysical characterization of chlorambucil anticancer ether lipid prodrugs. J Med Chem 2009; 52(10): 3408-15.
[http://dx.doi.org/10.1021/jm900091h] [PMID: 19402667]
[19]
May JP, Undzys E, Roy A, Li SD. Synthesis of a gemcitabine prodrug for remote loading into liposomes and improved therapeutic effect. Bioconjug Chem 2016; 27(1): 226-37.
[http://dx.doi.org/10.1021/acs.bioconjchem.5b00619] [PMID: 26673036]
[20]
Gabizon A, Amitay Y, Tzemach D, Gorin J, Shmeeda H, Zalipsky S. Therapeutic efficacy of a lipid-based prodrug of mitomycin C in pegylated liposomes: studies with human gastro-entero-pancreatic ectopic tumor models. J Control Release 2012; 160(2): 245-53.
[http://dx.doi.org/10.1016/j.jconrel.2011.11.019] [PMID: 22134116]
[21]
Kuznetsova NR, Sevrin C, Lespineux D, et al. Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer. J Control Release 2012; 160(2): 394-400.
[http://dx.doi.org/10.1016/j.jconrel.2011.12.010] [PMID: 22210161]
[22]
Kuznetsova NR, Stepanova EV, Peretolchina NM, et al. Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the Sialyl Lewis X selectin ligand. J Drug Target 2014; 22(3): 242-50.
[http://dx.doi.org/10.3109/1061186X.2013.862805] [PMID: 24313904]
[23]
Sarett SM, Kilchrist KV, Miteva M, Duvall CL. Conjugation of palmitic acid improves potency and longevity of siRNA delivered via endosomolytic polymer nanoparticles. J Biomed Mater Res A 2015; 103(9): 3107-16.
[http://dx.doi.org/10.1002/jbm.a.35413] [PMID: 25641816]
[24]
Daull P, Paterson CA, Kuppermann BD, Garrigue JS. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema. J Ocul Pharmacol Ther 2013; 29(2): 258-69.
[http://dx.doi.org/10.1089/jop.2012.0044] [PMID: 23331052]
[25]
Goldstein D, Gofrit O, Nyska A, Benita S. Anti-HER2 cationic immunoemulsion as a potential targeted drug delivery system for the treatment of prostate cancer. Cancer Res 2007; 67(1): 269-75.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2731] [PMID: 17210707]
[26]
Gong X, Moghaddam MJ, Sagnella SM, et al. Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine-a chemotherapy agent. Colloids Surf B Biointerfaces 2011; 85(2): 349-59.
[http://dx.doi.org/10.1016/j.colsurfb.2011.03.007] [PMID: 21477999]
[27]
Li F, Snow-Davis C, Du C, Bondarev ML, Saulsbury MD, Heyliger SO. Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles JoVE. (Journal of Visualized Experiments) 2016 Aug; 2(114)e54338
[http://dx.doi.org/10.3791/54338]
[28]
Zhao Y, Duan S, Zeng X, et al. Prodrug strategy for PSMA-targeted delivery of TGX-221 to prostate cancer cells. Mol Pharm 2012; 9(6): 1705-16.
[http://dx.doi.org/10.1021/mp3000309] [PMID: 22494444]
[29]
Yu BT, Sun X, Zhang ZR. Enhanced liver targeting by synthesis of N1-stearyl-5-Fu and incorporation into solid lipid nanoparticles. Arch Pharm Res 2003; 26(12): 1096-101.
[http://dx.doi.org/10.1007/BF02994764] [PMID: 14723346]
[30]
Gupta A, Asthana S, Konwar R, Chourasia MK. An insight into potential of nanoparticles-assisted chemotherapy of cancer using gemcitabine and its fatty acid prodrug:a comparative study. J Biomed Nanotechnol 2013; 9(5): 915-25.
[http://dx.doi.org/10.1166/jbn.2013.1591] [PMID: 23802424]
[31]
De Angel RE, Blando JM, Hogan MG, et al. Stearoyl gemcitabine nanoparticles overcome obesity-induced cancer cell resistance to gemcitabine in a mouse postmenopausal breast cancer model. Cancer Biol Ther 2013; 14(4): 357-64.
[http://dx.doi.org/10.4161/cbt.23623] [PMID: 23358472]
[32]
Lundberg BB, Risovic V, Ramaswamy M, Wasan KM. A lipophilic paclitaxel derivative incorporated in a lipid emulsion for parenteral administration. J Control Release 2003; 86(1): 93-100.
[http://dx.doi.org/10.1016/S0168-3659(02)00323-1] [PMID: 12490375]
[33]
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]
[34]
Du R, Zhong T, Zhang WQ, et al. Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma. Int J Nanomedicine 2014; 9: 3091-105.
[PMID: 25028548]
[35]
Wang Y, Li L, Jiang W, Larrick JW. Synthesis and evaluation of a DHA and 10-hydroxycamptothecin conjugate. Bioorg Med Chem 2005; 13(19): 5592-9.
[http://dx.doi.org/10.1016/j.bmc.2005.06.039] [PMID: 16084097]
[36]
Wang Y, Li L, Jiang W, Yang Z, Zhang Z. Synthesis and preliminary antitumor activity evaluation of a DHA and doxorubicin conjugate. Bioorg Med Chem Lett 2006; 16(11): 2974-7.
[http://dx.doi.org/10.1016/j.bmcl.2006.02.066] [PMID: 16563756]
[37]
Lepeltier E, Bourgaux C, Amenitsch H, et al. Influence of the nanoprecipitation conditions on the supramolecular structure of squalenoyled nanoparticles. Eur J Pharm Biopharm 2015; 96: 89-95.
[http://dx.doi.org/10.1016/j.ejpb.2015.07.004] [PMID: 26210010]
[38]
Raouane M, Desmaele D, Gilbert-Sirieix M, et al. Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma. J Med Chem 2011; 54(12): 4067-76.
[http://dx.doi.org/10.1021/jm2000272] [PMID: 21561161]
[39]
Cheikh-Ali Z, Caron J, Cojean S, et al. “Squalenoylcurcumin” nanoassemblies as water-dispersible drug candidates with antileishmanial activity. ChemMedChem 2015; 10(2): 411-8.
[http://dx.doi.org/10.1002/cmdc.201402449] [PMID: 25523035]
[40]
Sarpietro MG, Ottimo S, Paolino D, Ferrero A, Dosio F, Castelli F. Squalenoyl prodrug of paclitaxel: synthesis and evaluation of its incorporation in phospholipid bilayers. Int J Pharm 2012; 436(1-2): 135-40.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.034] [PMID: 22728161]
[41]
Borrelli S, Christodoulou MS, Ficarra I, et al. New class of squalene-based releasable nanoassemblies of paclitaxel, podophyllotoxin, camptothecin and epothilone A. Eur J Med Chem 2014; 85: 179-90.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.035] [PMID: 25084144]
[42]
Couvreur P, Stella B, Reddy LH, et al. Squalenoyl nanomedicines as potential therapeutics. Nano Lett 2006; 6(11): 2544-8.
[http://dx.doi.org/10.1021/nl061942q] [PMID: 17090088]
[43]
Arias JL, Reddy LH, Othman M, et al. Squalene based nanocomposites: a new platform for the design of multifunctional pharmaceutical theragnostics. ACS Nano 2011; 5(2): 1513-21.
[http://dx.doi.org/10.1021/nn1034197] [PMID: 21275408]
[44]
Pili B, Reddy LH, Bourgaux C, Lepêtre-Mouelhi S, Desmaële D, Couvreur P. Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer activity evaluation. Nanoscale 2010; 2(8): 1521-6.
[http://dx.doi.org/10.1039/c0nr00132e] [PMID: 20820745]
[45]
Radwan AA, Alanazi FK. Design and synthesis of new cholesterol-conjugated 5-Fluorouracil: a novel potential delivery system for cancer treatment. Molecules 2014; 19(9): 13177-87.
[http://dx.doi.org/10.3390/molecules190913177] [PMID: 25162958]
[46]
Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 2007; 25(10): 1149-57.
[http://dx.doi.org/10.1038/nbt1339] [PMID: 17873866]
[47]
Stevens PJ, Sekido M, Lee RJ. A folate receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug. Pharm Res 2004; 21(12): 2153-7.
[http://dx.doi.org/10.1007/s11095-004-7667-5] [PMID: 15648245]
[48]
Yadav K, Bhargava P, Bansal S, et al. Nature of the charged head group dictates the anticancer potential of lithocholic acid-tamoxifen conjugates for breast cancer therapy. MedChemComm 2015; 6(5): 778-87.
[http://dx.doi.org/10.1039/C4MD00289J]
[49]
Dalpiaz A, Contado C, Mari L, et al. Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid. Drug Deliv 2014; 21(3): 221-32.
[http://dx.doi.org/10.3109/10717544.2013.844744] [PMID: 24134683]
[50]
Duhem N, Danhier F, Pourcelle V, et al. Self-assembling doxorubicin-tocopherol succinate prodrug as a new drug delivery system: synthesis, characterization, and in vitro and in vivo anticancer activity. Bioconjug Chem 2014; 25(1): 72-81.
[http://dx.doi.org/10.1021/bc400326y] [PMID: 24328289]
[51]
Arouri A, Mouritsen OG. Anticancer double lipid prodrugs: liposomal preparation and characterization. J Liposome Res 2011; 21(4): 296-305.
[http://dx.doi.org/10.3109/08982104.2011.563365] [PMID: 21438721]
[52]
Feng L, Benhabbour SR, Mumper RJ. Oil-filled lipid nanoparticles containing 2′-(2-bromohexadecanoyl)-docetaxel for the treatment of breast cancer. Adv Healthc Mater 2013; 2(11): 1451-7.
[http://dx.doi.org/10.1002/adhm.201300017] [PMID: 23606545]
[53]
Pan D, Schmieder AH, Wang K, et al. Anti-angiogenesis therapy in the Vx2 rabbit cancer model with a lipase-cleavable Sn 2 taxane phospholipid prodrug using α(v)β3-targeted theranostic nanoparticles. Theranostics 2014; 4(6): 565-78.
[http://dx.doi.org/10.7150/thno.7581] [PMID: 24723979]
[54]
Liang CH, Ye WL, Zhu CL, et al. Synthesis of doxorubicin α-linolenic acid conjugate and evaluation of its antitumor activity. Mol Pharm 2014; 11(5): 1378-90.
[http://dx.doi.org/10.1021/mp4004139] [PMID: 24720787]
[55]
Zalipsky S, Saad M, Kiwan R, Ber E, Yu N, Minko T. Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor: insights of the mechanism of action. J Drug Target 2007; 15(7-8): 518-30.
[http://dx.doi.org/10.1080/10611860701499946] [PMID: 17671898]
[56]
Chen Q, Butler D, Querbes W, et al. Lipophilic siRNAs mediate efficient gene silencing in oligodendrocytes with direct CNS delivery. J Control Release 2010; 144(2): 227-32.
[http://dx.doi.org/10.1016/j.jconrel.2010.02.011] [PMID: 20170694]
[57]
Godeau G, Staedel C, Barthélémy P. Lipid-conjugated oligonucleotides via “click chemistry” efficiently inhibit hepatitis C virus translation. J Med Chem 2008; 51(15): 4374-6.
[http://dx.doi.org/10.1021/jm800518u] [PMID: 18605715]
[58]
Semalty A, Semalty M, Singh D, Rawat MS. Development and physicochemical evaluation of pharmacosomes of diclofenac. Acta Pharm 2009; 59(3): 335-44.
[http://dx.doi.org/10.2478/v10007-009-0023-x] [PMID: 19819829]
[59]
Muchow M, Maincent P, Müller RH. Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery. Drug Dev Ind Pharm 2008; 34(12): 1394-405.
[http://dx.doi.org/10.1080/03639040802130061] [PMID: 18665980]
[60]
Began G, Sudharshan E, Udaya Sankar K, Appu Rao AG. Interaction of curcumin with phosphatidylcholine: A spectrofluorometric study. J Agric Food Chem 1999; 47(12): 4992-7.
[http://dx.doi.org/10.1021/jf9900837] [PMID: 10606563]
[61]
Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 2007; 330(1-2): 155-63.
[http://dx.doi.org/10.1016/j.ijpharm.2006.09.025] [PMID: 17112692]
[62]
Singh C, Bhatt TD, Gill MS, Suresh S. Novel rifampicin-phospholipid complex for tubercular therapy: synthesis, physicochemical characterization and in-vivo evaluation. Int J Pharm 2014; 460(1-2): 220-7.
[http://dx.doi.org/10.1016/j.ijpharm.2013.10.043] [PMID: 24188983]
[63]
Montalbetti CA, Falque V. Amide bond formation and peptide coupling. Tetrahedron 2005; 61(46): 10827-52.
[http://dx.doi.org/10.1016/j.tet.2005.08.031]
[64]
Valeur E, Bradley M. Amide bond formation: beyond the myth of coupling reagents. Chem Soc Rev 2009; 38(2): 606-31.
[http://dx.doi.org/10.1039/B701677H] [PMID: 19169468]
[65]
Ashwanikumar N, Kumar NA, Asha Nair S, Vinod Kumar GS. 5-Fluorouracil-lipid conjugate: potential candidate for drug delivery through encapsulation in hydrophobic polyester-based nanoparticles. Acta Biomater 2014; 10(11): 4685-94.
[http://dx.doi.org/10.1016/j.actbio.2014.07.032] [PMID: 25110286]
[66]
Olbrich C, Gessner A, Kayser O, Müller RH. Lipid-drug-conjugate (LDC) nanoparticles as novel carrier system for the hydrophilic antitrypanosomal drug diminazenediaceturate. J Drug Target 2002; 10(5): 387-96.
[http://dx.doi.org/10.1080/1061186021000001832] [PMID: 12442809]
[67]
Neupane YR, Sabir MD, Ahmad N, Ali M, Kohli K. Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies. Nanotechnology 2013; 24(41)415102
[http://dx.doi.org/10.1088/0957-4484/24/41/415102] [PMID: 24061410]
[68]
Müller RH, Olbrich C. inventors; PharmaSol GmbH, assignee Lipid matrix-drug conjugates particle for controlled release of active ingredient United States patent US 6,770,299., 2004 Aug; 3.
[69]
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]
[70]
Patidar A, Thakur DS, Kumar P, Verma JH. A review on novel lipid based nanocarriers. Int J Pharm Pharm Sci 2010; 2(4): 30-5.
[71]
Gasco MR. Solid Lipid Nanospheres from Warm Micro-Emulsions: Improvements in SLN production for more efficient drug delivery. Pharmaceutical Technology Europe 1997; 9: 52-8.
[72]
Nagarajan R, Ruckenstein E. Molecular theory of microemulsions. Langmuir 2000; 16(16): 6400-15.
[http://dx.doi.org/10.1021/la991578t]
[73]
del Pozo-Rodríguez A, Delgado D, Gascón AR, Solinís MÁ. Lipid nanoparticles as drug/gene delivery systems to the retina. J Ocul Pharmacol Ther 2013; 29(2): 173-88.
[http://dx.doi.org/10.1089/jop.2012.0128] [PMID: 23286300]
[74]
Pandey R, Sharma S, Khuller GK. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis (Edinb) 2005; 85(5-6): 415-20.
[http://dx.doi.org/10.1016/j.tube.2005.08.009] [PMID: 16256437]
[75]
Nair R, Priya KV, Kumar KA, Badivaddin TM, Sevukarajan M. Formulation and evaluation of solid lipid nanoparticles of water soluble drug: isoniazid. Journal of Pharmaceutical Sciences and Research 2011; 3(5): 1256.
[76]
Yatvin MB, Stowell MH. inventors; Oregon Health Science University, assignee Covalent polar lipid-conjugates with biologically active compounds for use in salves United States patent US 6,387,876, 2002 May; 14
[77]
Liu J, Zhao D, Ma N, Luan Y. Highly enhanced leukemia therapy and oral bioavailability from a novel amphiphilicprodrug of cytarabine. RSC Advances 2016; 6(42): 35991-9.
[http://dx.doi.org/10.1039/C6RA02051H]
[78]
Bradley MO, Webb NL, Anthony FH, et al. Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clin Cancer Res 2001; 7(10): 3229-38.
[PMID: 11595719]
[79]
Chhikara BS, Mandal D, Parang K. Synthesis, anticancer activities, and cellular uptake studies of lipophilic derivatives of doxorubicin succinate. J Med Chem 2012; 55(4): 1500-10.
[http://dx.doi.org/10.1021/jm201653u] [PMID: 22276998]
[80]
Effenberger K, Breyer S, Schobert R. Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl and terpenyl hydrazones. Eur J Med Chem 2010; 45(5): 1947-54.
[http://dx.doi.org/10.1016/j.ejmech.2010.01.037] [PMID: 20133021]
[81]
Trevaskis NL, Kaminskas LM, Porter CJ. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity. Nat Rev Drug Discov 2015; 14(11): 781-803.
[http://dx.doi.org/10.1038/nrd4608] [PMID: 26471369]
[82]
Cui F, Shi K, Zhang L, Tao A, Kawashima Y. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release 2006; 114(2): 242-50.
[http://dx.doi.org/10.1016/j.jconrel.2006.05.013] [PMID: 16859800]
[83]
Paliwal R, Paliwal SR, Agrawal GP, Vyas SP. Biomimetic solid lipid nanoparticles for oral bioavailability enhancement of low molecular weight heparin and its lipid conjugates: in vitro and in vivo evaluation. Mol Pharm 2011; 8(4): 1314-21.
[http://dx.doi.org/10.1021/mp200109m] [PMID: 21598996]
[84]
Bala V, Rao S, Li P, Wang S, Prestidge CA. Lipophilic prodrugs of SN38: synthesis and in vitro characterization toward oral chemotherapy. Mol Pharm 2016; 13(1): 287-94.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00785] [PMID: 26623947]
[85]
Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C. Solid lipid nanoparticles for targeted brain drug delivery. Adv Drug Deliv Rev 2007; 59(6): 454-77.
[http://dx.doi.org/10.1016/j.addr.2007.04.011] [PMID: 17570559]
[86]
Lambert DM. Rationale and applications of lipids as prodrug carriers. Eur J Pharm Sci 2000; 11(Suppl. 2): S15-27.
[http://dx.doi.org/10.1016/S0928-0987(00)00161-5] [PMID: 11033424]
[87]
Gessner A, Olbrich C, Schröder W, Kayser O, Müller RH. The role of plasma proteins in brain targeting: species dependent protein adsorption patterns on brain-specific lipid drug conjugate (LDC) nanoparticles. Int J Pharm 2001; 214(1-2): 87-91.
[http://dx.doi.org/10.1016/S0378-5173(00)00639-6] [PMID: 11282243]
[88]
Urbinati G, de Waziers I, Slamiç M, et al. Knocking down TMPRSS2-ERG fusion oncogene by siRNA could be an alternative treatment to flutamide. Mol Ther Nucleic Acids 2016. 5e301
[http://dx.doi.org/10.1038/mtna.2016.16] [PMID: 27023109]
[89]
Ding Y, Wang W, Feng M, et al. A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy. Biomaterials 2012; 33(34): 8893-905.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.057] [PMID: 22979990]
[90]
Sharma P, Dube B, Sawant K. Synthesis of cytarabine lipid drug conjugate for treatment of meningeal leukemia: development, characterization and in vitro cell line studies. J Biomed Nanotechnol 2012; 8(6): 928-37.
[http://dx.doi.org/10.1166/jbn.2012.1464] [PMID: 23030001]
[91]
Ma P, Rahima Benhabbour S, Feng L, Mumper RJ. 2′-Behenoyl-paclitaxel conjugate containing lipid nanoparticles for the treatment of metastatic breast cancer. Cancer Lett 2013; 334(2): 253-62.
[http://dx.doi.org/10.1016/j.canlet.2012.08.009] [PMID: 22902506]
[92]
Chue P, Chue J. A review of paliperidone palmitate. Expert Rev Neurother 2012; 12(12): 1383-97.
[http://dx.doi.org/10.1586/ern.12.137] [PMID: 23237346]
[93]
Valetti S, Maione F, Mura S, et al. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor. J Control Release 2014; 192: 29-39.
[http://dx.doi.org/10.1016/j.jconrel.2014.06.039] [PMID: 24984010]
[94]
Couvreur P, Reddy LH, Mangenot S, et al. Discovery of new hexagonal supramolecular nanostructures formed by squalenoylation of an anticancer nucleoside analogue. Small 2008; 4(2): 247-53.
[http://dx.doi.org/10.1002/smll.200700731] [PMID: 18247384]
[95]
Daman Z, Ostad S, Amini M, Gilani K. Preparation, optimization and in vitro characterization of stearoyl-gemcitabine polymeric micelles: a comparison with its self-assembled nanoparticles. Int J Pharm 2014; 468(1-2): 142-51.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.021] [PMID: 24731731]
[96]
Alferiev IS, Iyer R, Croucher JL, et al. Nanoparticle-mediated delivery of a rapidly activatable prodrug of SN-38 for neuroblastoma therapy. Biomaterials 2015; 51: 22-9.
[http://dx.doi.org/10.1016/j.biomaterials.2015.01.075] [PMID: 25770994]
[97]
Wang JX, Sun X, Zhang ZR. Enhanced brain targeting by synthesis of 3′,5′-dioctanoyl-5-fluoro-2′-deoxyuridine and incorporation into solid lipid nanoparticles. Eur J Pharm Biopharm 2002; 54(3): 285-90.
[http://dx.doi.org/10.1016/S0939-6411(02)00083-8] [PMID: 12445558]
[98]
Chung WG, Sandoval MA, Sloat BR, Lansakara-P DS, Cui Z. Stearoyl gemcitabine nanoparticles overcome resistance related to the over-expression of ribonucleotide reductase subunit M1. J Control Release 2012; 157(1): 132-40.
[http://dx.doi.org/10.1016/j.jconrel.2011.08.004] [PMID: 21851843]
[99]
Painter GR, Almond MR, Trost LC, et al. Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections. Antimicrob Agents Chemother 2007; 51(10): 3505-9.
[http://dx.doi.org/10.1128/AAC.00460-07] [PMID: 17646420]
[100]
Fracasso PM, Picus J, Wildi JD, et al. Phase 1 and pharmacokinetic study of weekly docosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumor malignancies. Cancer Chemother Pharmacol 2009; 63(3): 451-8.
[http://dx.doi.org/10.1007/s00280-008-0756-0] [PMID: 18414864]
[101]
Irby D, Du C, Li F. Lipid-Drug Conjugate For Enhancing Drug Delivery. Mol Pharm 14(5): 1325-38.
[102]
Fitch RM, Wojdyla JK, Blackledge JA, McGhee WD. Anti-tumor activity of liposomal docetaxel prodrug MNK-010 on PC3 human prostate xenografts in mice
[103]
Rautio J, Kärkkäinen J, Sloan KB. Prodrugs - Recent approvals and a glimpse of the pipeline. Eur J Pharm Sci 2017; 109: 146-61.
[http://dx.doi.org/10.1016/j.ejps.2017.08.002] [PMID: 28782609]
[104]
Serigado JM, Izzy M, Kalia H. Novel therapies and potential therapeutic targets in the management of chronic hepatitis B. Eur J Gastroenterol Hepatol 2017; 29(9): 987-93.
[http://dx.doi.org/10.1097/MEG.0000000000000911] [PMID: 28538269]
[105]
Kim YC, Min KA, Jang DJ, et al. Practical approaches on the long-acting injections. J Pharm Investig 2019; 1-1.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy