The effect of PEG coating on in vitro cytotoxicity and in vivo disposition of topotecan loaded liposomes in rats

Dadashzadeh, Simin; Vali, A.M.; Rezaie, Mohammad Moien

doi:10.1016/j.ijpharm.2007.11.030

Cited by 66 publications

(37 citation statements)

References 29 publications

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“…More specifically, PEGylated liposomes with DOPC lipids showed a similar entrapment efficiency (75.6%) to previously prepared PEGylated formulations with DSPC, EPC and DPPC lipids (91.8%, 71.8%, and 84.9% respectively) [29]. These observations are in accordance with similar studies [50] and imply that shikonin incorporation could be strengthened by the presence of PEG on the outer surface of the lipid bilayer.…”

Section: Entrapment Efficiencysupporting

confidence: 88%

“…The same trends were obtained for the corresponding "empty" liposomes. Formulations with DSPE-PEG 2000 have less negative charge compared to liposomes without DSPE-PEG 2000 , a fact attributed to the "masking" of some of the anionic charges of DSPG by DSPE-PEG 2000 , which could explain the observed trend [40,47,50].…”

Section: ζ-Potentialmentioning

confidence: 99%

“…The different behaviour in terms of the release rate between the PEGylated and conventional liposomes may be attributed to the bilayer rigidity-the more rigid the bilayer, the slower the release of the drug [50]. Thus, it can be assumed that shikonin's release profile could be modified by the existence of PEG.…”

Section: Particle Size Distributionmentioning

confidence: 99%

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Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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Abstract:Liposomes are considered to be one of the most successful drug delivery systems.They apply nanotechnology to potentiate the therapeutic efficacy and reduce the toxicity of conventional medicines. Shikonin and alkannin, a pair of chiral natural naphthoquinone compounds, derived from Alkanna and Lithospermum species, are widely used due to their various pharmacological activities, mainly wound healing, antioxidant, anti-inflammatory and their recently established antitumor activity. The purpose of this study was to prepare conventional and PEGylated shikonin-loaded liposomal formulations and measure the effects of different lipids and polyethylene glycol (PEG) on parameters related to particle size distribution, the polydispersity index, the zeta potential, drug-loading efficiency and the stability of the prepared formulations. Three types of lipids were assessed (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DSPG)), separately and in mixtures, forming anionic liposomes with good physicochemical characteristics, high entrapment efficiencies (varying from 56.5 to 89.4%), satisfactory in vitro release profiles and good physical stability. The addition of the negatively charged DSPG lipids to DOPC, led to an increment in the drug's incorporation efficiency and reduced the particle size distribution. Furthermore, the shikonin-loaded PEGylated sample with DOPC/DSPG, demonstrated the most satisfactory characteristics. These findings are considered promising and could be used for further design and improvement of such formulations.

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Section: Entrapment Efficiencysupporting

confidence: 88%

Section: ζ-Potentialmentioning

confidence: 99%

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Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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“…Topotecan (9-[(dimethyl amino) methyl]-10-hydroxy-(20S) -camptothecin hydrochloride) is one of the two camptothecin analogues currently approved for clinical application by FDA for the treatment of refractory ovarian cancer and/or small-cell lung cancer, which are resistant to conventional chemotherapeutic agents. In addition, the combination of topotecan with other standard chemotherapeutic agents is progressively being used for optimized therapy [16,17]. Nowadays, there are considerable data in the literature addressing the toxicity level of topotecan.…”

Section: Introductionmentioning

confidence: 99%

Design, Development and Optimization of Topotecan Hydrochloride Solid Lipid Nanoparticles for Oral Chemotherapy

P³

et al. 2016

JNMR

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The objective of this research work was to formulate and evaluate solid lipid nanoparticles of anticancer drug topotecan hydrochloride in order to sustain its release and therefore improve its therapeutic outcomes. SLNs were prepared by hot micro emulsion method using glyceryl monostearate as lipid carrier and Tween 80 as surfactant in specific proportions. FT-IR and DSC studies revealed that there was no interaction between drug and lipid. The effect of drug: lipid ratio, surfactant concentration, speed and time of homogenizer on drug release, particle size and EE were studied. The results of particle size, encapsulation efficiency and in vitro drug release at 12hr fell between 111.9 nm and 255nm, 65.12% and 77.63%, and 72.31 and 79.79% respectively. Optimized formulation showed release of drug up to 73.47 % at 12 hrs, entrapment efficiency of 81.75% and particle size of 158.0 nm. The analysis of 3-D graphs revealed that parameters such as drug: lipid ratio and time of homogenization have a profound effect on both encapsulation efficiency and cumulative drug release. Scanning electron microscopy studies showed particles with disuniform surface and shape. The drug release from optimized formulation was found to fit best into first order kinetic model. It also showed almost linear regression in Higuchi's plot suggesting that diffusion is one of the mechanisms for drug release and n value of KorsmeyerPeppas plot was found to be 0.716 indicating that the drug release did not follow fickian diffusion controlled mechanism.

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“…Several patents (Burke, 1996, Perez-Soler et al, 1998 are available and numerous studies (Sugarman et al, 1996, Proulx et al, 2001, Burke et al, 1992, Saetern et al, 2004b, Watanabe et al, 2008, Eichhorn et al, 2007, Clements et al, 1996, Daoud et al, 1995 reported on liposomal formulations of camptothecins, whereof the majority of studies is on liposomal CPT-formulations investigated water soluble CPT-derivatives such as topotecan (Yang et al, 2012, Tardi et al, 2000, Liu et al, 2002, Subramanian et al, 1995, Zucker et al, 2012, Drummond et al, 2010, Dadashzadeh et al, 2008, irinotecan (Chou et al, 2003, Sadzuka, 2000, Sadzuka et al, 1998, Sadzuka et al, 1999, Sadzuka et al, 1997, Drummond et al, 2006, Zhang et al, 2012, Hattori et al, 2009), lurtotecan (MacKenzie et al, 2004, Loos et al, 2000, Desjardins et al, 2001, Colbern et al, 1998, SN-38 {Zhang, 2004Atyabi, 2009Sadzuka, 2005Lei, 2004#1330}, 9-nitro-CPT (Chen et al, 2008, Chen et al, 2006, Gilbert et al, 2002, Koshkina et al, 1999 and DB-67 (Bom et al, 2001. The focus on the present study is in contrast on poorly water soluble and lipophilic parent CPT-compound.…”

Section: Introductionmentioning

confidence: 99%

Liposomal formulations of poorly soluble camptothecin: drug retention and biodistribution

Flaten¹,

Chang²,

Phillips³

et al. 2012

Journal of Liposome Research

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Context: Camptothecin (CPT) represents a potent anticancer drug. Its therapeutic use however is impaired by both drug solubility, hydrolysis and protein interactions in vivo. Use of liposomes as drug formulation approach could overcome some of these challenges.Objective: The objective of this study was to perform a mechanistic study of the incorporation and retention of the lipophilic parent CPT-compound in different liposome formulations using radiolabeled CPT and thus be able to identify promising CPT delivery systems. In this context we also wanted to establish an appropriate mouse tumor model, in vivo scintigraphic imaging and biodistribution methodology for testing the most promising formulation. Materials and methods:CPT retention in various liposome formulations following incubation in buffer and serum was determined. The HT-29 mouse tumor model, 111 In-labeled liposomes as well as 3 H-labeled CPT were used to investigate the biodistribution of liposomes and drug. Results and discussion:The ability of different liposome formulations to retain CPT in buffer was influenced by the lipid concentration and the drug:lipid ratio rather than lipid composition.The tested formulations were cleared from the blood in the following order:CPT-solutionCPT-liposomes 111 In-labeled liposomes, and liposomes mainly accumulated in liver. Conclusion:Lipid composition did not influence CPT retention to the same extent as earlier observed in incorporation studies. The set up for the biodistribution study works well and is suited for future in vivo studies on CPT liposomes. The biodistribution study showed that liposomes circulated longer than free drug, but premature release of drug from liposomes occurred. Further studies to develop formulations with higher retention potential and prolonged circulation are desired.2

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The effect of PEG coating on in vitro cytotoxicity and in vivo disposition of topotecan loaded liposomes in rats

Cited by 66 publications

References 29 publications

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Design, Development and Optimization of Topotecan Hydrochloride Solid Lipid Nanoparticles for Oral Chemotherapy

Liposomal formulations of poorly soluble camptothecin: drug retention and biodistribution

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