Preparation, optimization and in vitro characterization of stearoyl-gemcitabine polymeric micelles: A comparison with its self-assembled nanoparticles

Daman, Zahra; Ostad, Seyed Nasser; Amini, Mohsen; Gilani, Kambiz

doi:10.1016/j.ijpharm.2014.04.021

Cited by 53 publications

(42 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…194 In another approach, gemcitabine nanoparticles were prepared by loading GemC18, a stearic acid amide derivative of gemcitabine, in PEG-poly(d,l-lactic) acid (PEG-PLA) polymeric micelles or by GemC18 self-assembling. 195 Both of the nanomedicines effectively reduced the viability of gemcitabine-resistant AsPC-1 cells in culture (IC 50 values, 58.88 and 46.34 µM, respectively), whereas the molar equivalent free gemcitabine did not show any significant cytotoxicity to AsPC-1 cells. The GemC18 self-assembled nanoparticles showed greater in vitro cellular uptake and cytotoxicity than the GemC18-PEG-PLA polymeric micellar nanoparticles (ie, drug uptake in Panc-1 cells, 37.55%±2.21% for GemC18 self-assembled nanoparticles, 28.60%±1.85% for GemC18-PEG-PLA polymeric micelles, and 30.11%±1.98% for GemC18 in solution).…”

Section: Polymeric Nanoparticlesmentioning

confidence: 94%

“…The GemC18 self-assembled nanoparticles showed greater in vitro cellular uptake and cytotoxicity than the GemC18-PEG-PLA polymeric micellar nanoparticles (ie, drug uptake in Panc-1 cells, 37.55%±2.21% for GemC18 self-assembled nanoparticles, 28.60%±1.85% for GemC18-PEG-PLA polymeric micelles, and 30.11%±1.98% for GemC18 in solution). 195 Gemcitabine nanoparticles were also prepared based on a gemcitabine-squalene conjugate (SQ-dFdC or SQ-Gem), which displayed a stronger antiproliferative and cytotoxic activity than gemcitabine. After orthotopic Panc-1 tumor-bearing mice were treated two times at a 4-day interval with either gemcitabine (20 mg/kg) or SQ-Gem (20 mg/kg), SQ-Gem was more effective than gemcitabine in inhibiting the tumor growth.…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

See 1 more Smart Citation

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

View full text Add to dashboard Cite

Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

show abstract

Section: Polymeric Nanoparticlesmentioning

confidence: 94%

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

View full text Add to dashboard Cite

show abstract

“…31,32 In brief, 100 μL of pyrene solution (0.1 mg/mL in benzene) was aliquoted into a series of 10 mL test tubes, and the solvent benzene was evaporated under nitrogen stream at room temperature for 5 hours. A series of aqueous polymeric solutions (concentrations ranging from 10 ng/mL to 1 mg/mL) were added separately to obtain the final concentration of pyrene of 1 μg/mL, and then were sonicated for 20 minutes at room temperature, and finally were incubated at 45°C for 4 hours.…”

Section: Cells and Animalsmentioning

confidence: 99%

Preparation, characterization, in vivo pharmacokinetics, and biodistribution of polymeric micellar dimethoxycurcumin for tumor targeting

Liu¹,

Xu²,

Jiang³

et al. 2015

IJN

View full text Add to dashboard Cite

Dimethoxycurcumin (DMC) is an analog of curcumin with superior efficacy in various disease models. Currently, drug delivery system research on DMC is very limited, and it has become a huge challenge to realize further developments and clinical applications. In the present study, a kind of amphiphilic block copolymer, N- t -butoxycarbonyl-phenylalanine terminated monomethoxyl poly (ethylene glycol)-b-poly (ε-caprolactone), or mPEG-PCL-Phe(Boc), was prepared from monomethoxyl poly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL) with its hydroxyl terminal chemically converted into N- t -butoxycarbonyl-phenylalanine (Boc-Phe). This copolymer was determined to have a fairly low critical micelle concentration (2.56×10 −3 mg/mL) and passive targeting potential to tumor tissue, and thus was applied to develop a polymeric micellar formulation of DMC for the first time. The DMC-loaded micelles prepared by thin-film hydration method had typical shell–core structure, with an average particle size of 17.9±0.4 nm and a polydispersity index of 0.045±0.011. The drug loading capacity and entrapment efficiency were 9.94%±0.15% and 97.22%±0.18%, respectively, indicating a high-affinity interaction between DMC and the copolymer. At a concentration of 2 mg/mL, the reconstituted micelle solution could be maintained for at least 10 days at room temperature, and displayed a low initial burst release followed by a sustained release in vitro. Pharmacokinetic study in rats revealed that in vivo drug exposure of DMC was significantly increased and prolonged by intravenously administering DMC-loaded micelles when compared with the same dose of free DMC dissolved in dimethyl sulfoxide. Furthermore, in vivo distribution results from tumor-bearing nude mice demonstrated that this micellar formulation significantly changed the biodistribution profile of DMC and increased drug accumulation in tumors. Therefore, the polymeric micellar formulation of DMC, based on the amphiphilic block copolymer, mPEG-PCL-Phe(Boc), could provide a desirable method for delivering DMC, especially for applications in cancer therapy.

show abstract

“…In the next step, the morphology, release behavior and cytotoxicity of the selected formulations were investigated. Human pancreas cancer AsPC-1 cells were chosen as the model for cancer cells because they were demonstrated to be highly resistant to gemcitabine (17). The in vivo antitumor activity in balb/c mice bearing AsPC-1 cancer xenogafts was also evaluated.…”

Section: Introductionmentioning

confidence: 99%

Polymeric Micelles of PEG-PLA Copolymer as a Carrier for Salinomycin Against Gemcitabine-Resistant Pancreatic Cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

Preparation, optimization and in vitro characterization of stearoyl-gemcitabine polymeric micelles: A comparison with its self-assembled nanoparticles

Cited by 53 publications

References 30 publications

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Preparation, characterization, in vivo pharmacokinetics, and biodistribution of polymeric micellar dimethoxycurcumin for tumor targeting

Polymeric Micelles of PEG-PLA Copolymer as a Carrier for Salinomycin Against Gemcitabine-Resistant Pancreatic Cancer

Contact Info

Product

Resources

About