Liposome-based delivery systems for ginsenoside Rh2: in vitro and in vivo comparisons
Source abstract
Abstract
The Ginsenoside Rh2 (Rh2) has been shown to possess anti-cancer properties both in vitro and in vivo. However, the poor bioavailability and fast plasma elimination limit the further clinical applications of Rh2 for cancer treatments. In the present study, three types of Rh2-loaded liposomes including Rh2-loaded normal liposome (Rh2-LP), Rh2-loaded cationic liposome (Rh2-CLP), and Rh2-loaded Methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) liposome (Rh2-PLP) have been optimized and prepared with mean particle size of 80–125 nm. Compared to Rh2-LP, surface modifications with mPEG or octadecylamine significantly improve the physicochemical and biological properties both in vitro and in vivo. Moreover, PLP presented better tumor accumulation of the fluorescent cyanine dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) in HepG2-xenografted nude mice than CLP (1.3-fold) or LP (1.6-fold) and prolong the resident time of DiR in tumor and organs (more than 24 h). The in vivo anti-cancer efficacy assessments indicate that Rh2-PLP presents the most activity on suppressing tumor growth in HepG2-xenografted mice than Rh2-LP and Rh2-CLP and without any significant toxicity. Our results indicate that mPEG-PLA modified liposome should be a potential and promising strategy to enhance the therapeutic index for anti-cancer agents.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Ginseng Biological Effects and Applications · Nanoparticle-Based Drug Delivery · Cytomegalovirus and herpesvirus research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (53)
Show source-provided references
1. Abu-Lila A, Suzuki T, Doai Y, Ishida T, Kiwada H (2009) Oxaliplatin targeting to angiogenic vessels by PEGylated cationic liposomes suppresses the angiogenesis in a dorsal air sac mouse model. J Control Release 134:18–2510.1016/j.jconrel.2008.10.018 ↗
2. Abu-Lila AS, Ishida T, Kiwada H (2010) Targeting anticancer drugs to tumor vasculature using cationic liposomes. Pharm Res 27:1171–118310.1007/s11095-010-0110-1 ↗
3. Abu-Lila AS, Eldin NE, Ichihara M, Ishida T, Kiwada H (2012) Multiple administration of PEG-coated liposomal oxaliplatin enhances its therapeutic efficacy: a possible mechanism and the potential for clinical application. Int J Pharm 438:176–18310.1016/j.ijpharm.2012.08.030 ↗
4. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65:36–4810.1016/j.addr.2012.09.037 ↗
5. Andresen TL, Jensen SS, Jørgensen K (2005) Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. Prog Lipid Res 44:68–9710.1016/j.plipres.2004.12.001 ↗
6. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–20510.1016/j.jconrel.2011.06.001 ↗
7. Biswas S, Dodwadkar NS, Deshpande PP, Parab S, Torchilin VP (2013) Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity. Eur J Pharm Biopharm 84:517–52510.1016/j.ejpb.2012.12.021 ↗
8. Cai S, Yang Q, Bagby TR, Forrest ML (2011) Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles. Adv Drug Deliv Rev 63:901–90810.1016/j.addr.2011.05.017 ↗
9. Chen X, Wang X, Wang Y, Yang L, Hu J, Xiao W, Fu A, Cai L, Li X, Ye X, Liu Y, Wu W, Shao X, Mao Y, Wei Y, Chen L (2010) Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide. J Control Release 45:17–2510.1016/j.jconrel.2010.03.007 ↗
10. Cheng CC, Yang SM, Huang CY, Chen JC, Chang WM, Hsu SL (2005) Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemother Pharmacol 55:531–54010.1007/s00280-004-0919-6 ↗
11. Coimbra M, Isacchi B, van Bloois L, Torano JS, Ket A, Wu X, Broere F, Metselaar JM, Rijcken CJ, Storm G, Bilia R, Schiffelers RM (2011) Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. Int J Pharm 416:433–44210.1016/j.ijpharm.2011.01.056 ↗
12. Dadashzadeh S, Mirahmadi N, Babaei MH, Vali AM (2010) Peritoneal retention of liposomes: effects of lipid composition, PEG coating and liposome charge. J Control Release 148:177–18610.1016/j.jconrel.2010.08.026 ↗
13. Elmowafy M, Viitala T, Ibrahim HM, Abu-Elyazid SK, Samy A, Kassem A, Yliperttula M (2013) Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake. Eur J Pharm Sci 50:161–17110.1016/j.ejps.2013.06.012 ↗
14. Gref R, Domb A, Quellec P, Blunk T, Müller RH, Verbavatz JM, Langer R (1995) The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev 16:215–22310.1016/0169-409X(95)00026-4 ↗
15. Gu Y, Wang GJ, Sun JG, Jia YW, Wang W, Xu MJ, Lv T, Zheng YT, Sai Y (2009) Pharmacokinetic characterization of ginsenoside Rh2, an anticancer nutrient from ginseng, in rats and dogs. Food Chem Toxicol 47:2257–226810.1016/j.fct.2009.06.013 ↗
16. Ishida T, Harashima H, Kiwada H (2002) Liposome clearance. Biosci Rep 22:197–22410.1023/A:1020134521778 ↗
17. Justo OR, Moraes AM (2005) Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment. J Pharm Pharmacol 57:23–3010.1211/0022357055092 ↗
18. Kazakov S, Levon K (2006) Liposome-nanogel structures for future pharmaceutical applications. Curr Pharm Des 12:4713–472810.2174/138161206779026281 ↗
19. Kim HK, Davaa E, Myung CS, Park JS (2010) Enhanced siRNA delivery using cationic liposomes with new polyarginine-conjugated PEG-lipid. Int J Pharm 392:141–14710.1016/j.ijpharm.2010.03.047 ↗
20. Kim CE, Lim SK, Kim JS (2012) In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer. J Control Release 157:190–19510.1016/j.jconrel.2011.09.066 ↗
21. Kolate A, Baradia D, Patil S, Vhora I, Kore G, Misra A (2014) PEG-a versatile conjugating ligand for drugs and drug delivery systems. J Control Release 192:67–8110.1016/j.jconrel.2014.06.046 ↗
22. Langner M, Kral TE (1999) Liposome-based drug delivery systems. Pol J Pharmacol 51:211–222
23. Li SD, Huang L (2010) Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J Control Release 145:178–18110.1016/j.jconrel.2010.03.016 ↗
24. Li X, Ding L, Xu Y, Wang Y, Ping Q (2009) Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int J Pharm 373:116–12310.1016/j.ijpharm.2009.01.023 ↗
25. Maeda H (2012) Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J Control Release 164:138–14410.1016/j.jconrel.2012.04.038 ↗
26. Maeda H, Sawa T, Konno T (2001) Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 74:47–6110.1016/S0168-3659(01)00309-1 ↗
27. Maeda H, Bharate GY, Daruwalla J (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur J Pharm Biopharm 71:409–41910.1016/j.ejpb.2008.11.010 ↗
28. Mei L, Fu L, Shi K, Zhang Q, Liu Y, Tang J, Gao H, Zhang Z, He Q (2014) Increased tumor targeted delivery using a multistage liposome system functionalized with RGD, TAT and cleavable PEG. Int J Pharm 468:26–3810.1016/j.ijpharm.2014.04.008 ↗
29. Mirahmadi N, Babaei MH, Vali AM, Dadashzadeh S (2010) Effect of liposome size on peritoneal retention and organ distribution after intraperitoneal injection in mice. Int J Pharm 383:7–1310.1016/j.ijpharm.2009.08.034 ↗
30. Mohammed AR, Bramwell VW, Kirby DJ, McNeil SE, Perrie Y (2010) Increased potential of a cationic liposome-based delivery system: enhancing stability and sustained immunological activity in pre-clinical development. Eur J Pharm Biopharm 76:404–41210.1016/j.ejpb.2010.09.008 ↗
31. Mu CF, Balakrishnan P, Cui FD, Yin YM, Lee YB, Choi HG, Yong CS, Chung SJ, Shim CK, Kim DD (2010) The effects of mixed MPEG–PLA/Pluronic® copolymer micelles on the bioavailability and multidrug resistance of docetaxel. Biomaterials 31:2371–237910.1016/j.biomaterials.2009.11.102 ↗
32. Naicker K, Ariatti M, Singh M (2014) PEGylated galactosylated cationic liposomes for hepatocytic gene delivery. Colloids Surf B 122:482–49010.1016/j.colsurfb.2014.07.010 ↗
33. Nakamura K, Yamashita K, Itoh Y, Yoshino K, Nozawa S, Kasukawa H (2012) Comparative studies of polyethylene glycol-modified liposomes prepared using different PEG-modification methods. Biochim Biophys Acta 1818:2801–280710.1016/j.bbamem.2012.06.019 ↗
34. Oku N, Namba Y (1994) Long-circulating liposomes. Crit Rev Ther Drug Carrier Syst 11:231–270
35. Paliwal SR, Paliwal R, Agrawal GP, Vyas SP (2011) Liposomal nanomedicine for breast cancer therapy. Nanomedicine 6:1085–110010.2217/nnm.11.72 ↗
36. Qian T, Cai Z, Wong RN, Jiang ZH (2005) Liquid chromatography/mass spectrometric analysis of rat samples for in vivo metabolism and pharmacokinetic studies of ginsenoside Rh2. Rapid Commun Mass Spectrom 19:3549–355410.1002/rcm.2232 ↗
37. Resina S, Prevot P, Thierry AR (2009) Physico-chemical characteristics of lipoplexes influence cell uptake mechanism and transfection efficacy. PLoS One 4:6058–606910.1371/journal.pone.0006058 ↗
38. Saengkrit N, Saesoo S, Srinuanchai W, Phunpee S, Ruktanonchai UR (2014) Influence of curcumin-loaded cationic liposome on anticancer activity for cervical cancer therapy. Colloids Surf B 114:349–35610.1016/j.colsurfb.2013.10.005 ↗
39. She ZG, Liu XY, Kotamraju VR, Ruoslahti E (2014) Clot-targeted micellar formulation improves anticoagulation efficacy of bivalirudin. ACS Nano 8:10139–1014910.1021/nn502947b ↗
40. Shehata T, Ogawara K, Higaki K, Kimura T (2008) Prolongation of residence time of liposome by surface-modification with mixture of hydrophilic polymers. Int J Pharm 359:272–27910.1016/j.ijpharm.2008.04.004 ↗
41. Sun S, Wang CZ, Tong R, Li XL, Fishbein A, Wang Q, He TC, Du W, Yuan CS (2010) Effects of steaming the root of Panax notoginseng on chemical composition and anticancer activities. Food Chem 118:307–31410.1016/j.foodchem.2009.04.122 ↗
42. Szebeni J, Muggia F, Gabizon A, Barenholz Y (2011) Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Adv Drug Deliv Rev 63:1020–103010.1016/j.addr.2011.06.017 ↗
43. Tagami T, Suzuki T, Matsunaga M, Nakamura K, Moriyoshi N, Ishida T, Kiwada H (2012) Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery. Int J Pharm 422:280–28910.1016/j.ijpharm.2011.10.059 ↗
44. van den Hoven JM, Nemes R, Metselaar JM, Nuijen B, Beijnen JH, Storm G, Szebeni J (2013) Complement activation by PEGylated liposomes containing prednisolone. Eur J Pharm Sci 49:265–27110.1016/j.ejps.2013.03.007 ↗
45. Wang H, Zhao P, Liang X, Gong X, Song T, Niu R, Chang J (2010) Folate-PEG coated cationic modified chitosan–cholesterol liposomes for tumor-targeted drug delivery. Biomaterials 3:4129–413810.1016/j.biomaterials.2010.01.089 ↗
46. Wen Z, Yan Z, Hu K, Pang Z, Cheng X, Guo L, Zhang Q, Jiang X, Fang L, Lai R (2011) Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release 151:131–13810.1016/j.jconrel.2011.02.022 ↗
47. Yan Z, Wang F, Wen Z, Zhan C, Feng L, Liu Y, Wei X, Xie C, Lu W (2012) LyP-1-conjugated PEGylated liposomes: a carrier system for targeted therapy of lymphatic metastatic tumor. J Control Release 157:118–12510.1016/j.jconrel.2011.07.034 ↗
48. Yang T, Cui FD, Choi MK, Cho JW, Chung SJ, Shim CK, Kim DD (2007) Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation. Int J Pharm 338:317–32610.1016/j.ijpharm.2007.02.011 ↗
49. Yang ZZ, Li JQ, Wang ZZ, Dong DW, Qi XR (2014) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–523910.1016/j.biomaterials.2014.03.017 ↗
50. Yoshino K, Nakamura K, Terajima Y, Kurita A, Matsuzaki T, Yamashita K, Isozaki M, Kasukawa H (2012) Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods. Biochim Biophys Acta 1818:2901–290710.1016/j.bbamem.2012.07.011 ↗
51. Zalba S, Navarro I, Trocóniz IF, Tros de Ilarduya C, Garrido MJ (2012) Application of different methods to formulate PEG-liposomes of oxaliplatin: evaluation vitro and in vivo. Eur J Pharm Biopharm 81:273–28010.1016/j.ejpb.2012.02.007 ↗
52. Zhang J, Zhou F, Wu X, Gu Y, Ai H, Zheng Y, Li Y, Zhang X, Hao G, Sun J, Peng Y, Wang G (2010) 20(S)-ginsenoside Rh2 noncompetitively inhibits P-glycoprotein in vitro and in vivo: a case for herb-drug interactions. Drug Metab Dispos 38:2179–218710.1124/dmd.110.034793 ↗
53. Zhao Y, Li J, Yu H, Wang G, Liu W (2012) Synthesis and characterization of a novel polydepsipeptide contained tri-block copolymer (mPEG-PLLA-PMMD) as self-assembly micelle delivery system for paclitaxel. Int J Pharm 430:282–29110.1016/j.ijpharm.2012.03.043 ↗