Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on the<i>in vitro</i>and<i>in vivo</i>performance of micelles

Ukawala, Mukesh; Rajyaguru, Tushar; Chaudhari, Kiran; Manjappa, Arehalli S.; Pimple, Smita S.; Babbar, Anil Kumar; Mathur, Rashi; Mishra, Anil K.; Murthy, R. S. R.

doi:10.3109/10717544.2012.657721

Cited by 37 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 All kinds of macromolecular architectures based on PCL and PEG have been proposed from classical diblock copolymers to triblock copolymers, dendrimer-derived, star or miktoarm architectures. [9][10][11][12][13] The availability of a variety of macromolecular architectures and compositions has proved the potential of these polymer systems for cancer therapy, and the impact of PCL-PEG copolymer amphiphilicity on the formation and shape of self-assemblies, 14,15 drug loading, formulation stability 12,16 and cellular internalization [17][18][19] have been studied. It was also demonstrated that PCL-PEG copolymers could act as modulators of the drug efflux transporter P-glycoprotein in vitro and therefore they could be beneficial for the problematic treatment of multidrug resistant (MDR) cancer tumors.…”

Section: Introductionmentioning

confidence: 99%

PCL–PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems

et al. 2016

View full text Add to dashboard Cite

International audienceThe development of flexible drug delivery systems that can be tuned as a function of the drug to bedelivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly-(e-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design weresynthesized by thiol–yne photochemistry. The grafting density and the copolymer amphiphilicity wereeasily controlled via the reaction parameters: concentration, reaction time, PEG length and the molarratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behaviorof the copolymers was studied and a correlation between the composition of PCL-g-PEG and thenanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L1)was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with variousdrugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance incancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug(clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratiois discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chainsshowed higher toxicity compared to their more hydrophilic counterparts

show abstract

Section: Introductionmentioning

confidence: 99%

PCL–PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In this study, the CMC value was determined to be 0.35 μg/mL, in the same order of magnitude and much lower than mPEG‐PCL, compared with some other studied polymeric micelles. The lower CMC value, maybe due to the strong the hydrophobic interaction between the hydrophobic segments, enables the use of this novel mixed micelles as drug carriers with the stability to maintain a micelle structure against dissociation and precipitation in blood due to dilution …”

Section: Resultsmentioning

confidence: 99%

“…The lower CMC value, maybe due to the strong the hydrophobic interaction between the hydrophobic segments, enables the use of this novel mixed micelles as drug carriers with the stability to maintain a micelle structure against dissociation and precipitation in blood due to dilution. 28…”

Section: The Tem Of Gna-mmsmentioning

confidence: 99%

A novel drug delivery system of mixed micelles based on poly(ethylene glycol)‐poly(lactide) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) for gambogenic acid

Lin

Zhu

Yan

et al. 2019

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)‐poly(lactide) (mPEG‐PLA) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) (mPEG‐PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA‐loaded mixed polymeric micelles (GNA‐MMs) was prepared by cosolvent evaporation method. The mean average size of GNA‐MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA‐MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA‐MMs were spherical with “core‐shell” structures. Compared with free GNA solution, in vitro release of GNA from GNA‐MMs showed a two‐phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA‐MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC50 values on HepG2 cells for GNA‐MMs and free GNA were (5.67 ± 0.02) μM and (9.02 ± 0.03) μM, respectively. In addition, GNA‐MMs significantly increased the HepG2 cellular apoptosis in a concentration‐dependent manner. In conclusion, the results showed that mPEG‐PLA/mPEG‐PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect.

show abstract

“…Micellar complexation may moreover modify the drug disposition in the body by preventing uncontrolled drug distribution and favoring drug accumulation in solid tumors where the discontinuity of the capillaries and the lack of an efficient lymphatic drainage supports the entrapment and retention of nanoparticulate systems such as micelles, liposomes or soluble macromolecules ( 39 , 40 , 47 ). The micellar complexation of Paclitaxel and Etoposide is regarded with great interest to improve their bioavailability ( 48 , 49 ) overcoming the adverse reactions associated with the currently marketed formulations. Indeed, apart from Abraxane®, consisting in nanoparticles of Paclitaxel and human serum albumin, all the other marketed formulations of Paclitaxel and Etoposide contain excipients such as Cremophor-EL, ethanol, benzyl alcohol, polysorbate-80 which have been associated with serious side effects ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Preparation and Evaluation of a Novel Class of Amphiphilic Amines as Antitumor Agents and Nanocarriers for Bioactive Molecules

et al. 2016

View full text Add to dashboard Cite

PurposeWe describe a novel class of antitumor amphiphilic amines (RCn) based on a tricyclic amine hydrophilic head and a hydrophobic linear alkyl tail of variable length.MethodsWe tested the lead compound, RC16, for cytotoxicity and mechanism of cell death in several cancer cell lines, anti tumor efficacy in mouse tumor models, and ability to encapsulate chemotherapy drugs.ResultsThese compounds displayed strong cytotoxic activity against cell lines derived from both pediatric and adult cancers. The IC50 of the lead compound, RC16, for normal cells including human keratinocytes, human fibroblasts and human umbilical vein endothelial cells was tenfold higher than for tumor cells. RC16 exhibited significant antitumor effects in vivo using several human xenografts and a metastatic model of murine neuroblastoma by both intravenous and oral administration routes. The amphiphilic character of RC16 triggered a spontaneous molecular self-assembling in water with formation of micelles allowing complexation of Doxorubicin, Etoposide and Paclitaxel. These micelles significantly improved the in vitro antitumor activity of these drugs as the enhancement of their aqueous solubility also improved their biologic availability.ConclusionsRC16 and related amphiphilic amines may be useful as a novel cancer treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-016-1999-9) contains supplementary material, which is available to authorized users.

show abstract

Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on thein vitroandin vivoperformance of micelles

Abstract: (2012) Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on the invitro and invivo performance of micelles, Drug Delivery, 19:3,[155][156][157][158][159][160][161][162][163][164][165][166][167]

Cited by 37 publications

References 48 publications

PCL–PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems

PCL–PEG graft copolymers with tunable amphiphilicity as efficient drug delivery systems

A novel drug delivery system of mixed micelles based on poly(ethylene glycol)‐poly(lactide) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) for gambogenic acid

Preparation and Evaluation of a Novel Class of Amphiphilic Amines as Antitumor Agents and Nanocarriers for Bioactive Molecules

Contact Info

Product

Resources

About