Effects of organic solvents on drug incorporation into polymeric carriers and morphological analyses of drug-incorporated polymeric micelles

Harada, Yoshiko; Yamamoto, Tatsuhiro; Sakai, Masaru; Saiki, Takanao; Kawano, Keiichi; Maitani, Yoshie; Yokoyama, M.

doi:10.1016/j.ijpharm.2010.11.016

Cited by 22 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One is that the remains of an organic solvent might be hazardous because of incomplete evaporation or dialysis. Another one is that the size distribution of drug-loaded micelles might be non-uniform due to the asynchronous precipitation of drugs and polymers from an organic solvent [9].…”

Section: Introductionmentioning

confidence: 99%

Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure

Wang

Xing

Fang

et al. 2013

Phil. Trans. R. Soc. A.

View full text Add to dashboard Cite

Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG–PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG–PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of p K a and to evaluate the compatibility of drugs with PEG–PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG–PE micelle-based drug encapsulation and might enlighten the future study on drug–polymer compatibility for other polymeric micelles.

show abstract

Section: Introductionmentioning

confidence: 99%

Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure

Wang

Xing

Fang

et al. 2013

Phil. Trans. R. Soc. A.

View full text Add to dashboard Cite

show abstract

“…Compared to other preparation methods, the cosolvent evaporation method shown not only high EE%, excellent physicochemical properties but also could high‐yield and scale‐up feasibility (Table ). Those results no differences with Harada …”

Section: Resultsmentioning

confidence: 52%

“…MRT 0-t of the GNA-MMs and free GNA solutions were (329 23. ± 30.00) minutes and (147.75 ± 22.71) minutes, respectively.…”

mentioning

confidence: 97%

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

“…It even shows low solubility in many organic solvents such as chloroform and ethanol [6, 7]. Therefore, CPT is hard to be formulated into some commonly used carriers via a simple method of solvent evaporation.…”

Section: Introductionmentioning

confidence: 99%

The self-assembling camptothecin-tocopherol prodrug: An effective approach for formulating camptothecin

Liu

Wang

et al. 2015

Biomaterials

View full text Add to dashboard Cite

Camptothecin (CPT) is a potent antitumor agent and functions via inhibiting the activity of topoisomerase I during DNA replication. However, the clinical application of CPT has been greatly hindered by its extremely poor solubility, the instability of its active lactone ring in blood stream, as well as the non-specific toxicity to normal tissues. In addition, most of the formulations developed so far are not applicable for formulating CPT. In this study, two novel CPT prodrugs were developed by conjugating CPT to α-tocopherol via a carbonate ester bond (CPT-VE) or disulfide linkage (CPT-S-S-VE). Both CPT prodrugs were able to self-assemble into nanofibers with the facilitation of a PEG5K-Fmoc-VE2-based nanomicellar carrier. Both prodrug nanoassemblies exhibited excellent stability. Fluorescence quenching, UV absorbance, and FT-IR studies demonstrated strong interactions between carrier and prodrugs, including hydrophobic interaction, π-π stacking, as well as hydrogen bonding. NMR studies suggested that prodrugs were successfully incorporated into PEG5K-Fmoc-VE2 during self-assembly process. In vitro, PEG5K-Fmoc-VE2/CPT-S-S-VE presented significantly higher level of cytotoxicity on tumor cells compared to PEG5K-Fmoc-VE2/CPT-VE. Biodistribution study showed that CPT-S-S-VE formulated in PEG5K-Fmoc-VE2 micelles was effectively converted to parent CPT following delivery to tumor tissues. Finally, PEG5K-Fmoc-VE2/CPT-S-S-VE nanofibers showed superior tumor growth inhibition in an aggressive murine breast cancer model (4T1.2).

show abstract

Effects of organic solvents on drug incorporation into polymeric carriers and morphological analyses of drug-incorporated polymeric micelles

Cited by 22 publications

References 30 publications

Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure

Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure

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

The self-assembling camptothecin-tocopherol prodrug: An effective approach for formulating camptothecin

Contact Info

Product

Resources

About