Drug solubilization by amino acid based polymeric nanoparticles: Characterization and biocompatibility studies

(2015) Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin, Drug Delivery, 22:1, 58-68, DOI: 10.3109/10717544.2014 Methods: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly ("-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and "-caprolactone as raw materials. Its structure was characterized by 1 H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. Results: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 Â 10 5 times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model (R 2 abj ¼ 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT 0-1 , t 1/2z and AUC 0-1 of Curcuminloaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. Conclusions: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.

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“…All determinations were done for three times (Dutta & Dey, 2011). The results were calculated based on Equation (3) …”

Section: Hemolysis Test Of Copolymersmentioning

confidence: 99%

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

et al. 2014

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“…The control group received the Z-GP-Dox cosolvent (45% propylene glycerol) by intravenous injection at a dose of 10 mg/kg body weight, whereas the micelle group received ZGD-MNs at the same dose. At predetermined time points (5,15, and 30 minutes, and 1, 2, 4, 6, and 8 hours) after drug administration, the rats were rendered unconscious for blood …”

Section: Pharmacokinetic Study Of Z-gp-doxmentioning

confidence: 99%

“…27 The plasma cardiac output (Q co ) for rats was calculated as 2.69 L/hour. The mass balance equations (1)(2)(3)(4)(5)(6)(7)(8) for the model are shown as follows: …”

Section: Pbpk Modeling and Fittingmentioning

confidence: 99%

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Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Zhang¹,

Zhang²,

Li³

et al. 2015

IJN

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Z-GP-Dox, the FAPα (fibroblast activation protein-α)-based doxorubicin prodrug, demonstrates excellent tumor targeting effects and a favorable toxicokinetic profile. However, the insoluble nature of Z-GP-Dox becomes a significant barrier to drug administration, particularly when it comes to the clinical stage. Here we developed a nanomicelle system to facilitate the systemic delivery of Z-GP-Dox, and evaluated its disposition in rats following administration of the micelles using a physiologically-based pharmacokinetic model. Z-GP-Dox-loaded mixed nanomicelles (ZGD-MNs) were prepared by dispersion of an ethanol solution of Z-GP-Dox, lecithin, and sodium oleate in water. The obtained ZGD-MNs were 86.6 nm in size with a drug loading of 14.03%. ZGD-MNs were fairly stable in phosphate-buffered saline and showed satisfactory physical and chemical stability over a 2-week observation period. Accumulative drug release was more than 56% within 24 hours. Further, the physiologically-based pharmacokinetic rat model consisting of various organs (ie, heart, liver, spleen, lung, kidney, and intestine) was fitted to the experimental data following administration of ZGD-loaded cosolvent (control) or micelles. Derived partition coefficient values revealed that the nanomicelles significantly altered the biodistribution of Z-GP-Dox. Of note, drug distribution to the lung, liver, and spleen was greatly enhanced and the fold change ranged from 2.4 to 33. In conclusion, this is the first report of a mixed micelle system being a viable carrier for delivery of Z-GP-Dox. Also, the pharmacokinetic behavior of Z-GP-Dox was satisfactorily described by the physiologically-based pharmacokinetic model.

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“…[22] Also, in recent years, increasing interest has been paid to the incorporation of biodegradable and biocompatible moieties based on amino acids in synthetic polymers to allow good interactions of polymer with biological systems. [23][24][25][26][27] These advanced synthetic polymers referred as synthetic co-polypeptides have attracted interest as models for natural polypeptides and proteins [28] with applications from nanotechnology to tissue engineering. [18] technique.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of diethyl-dithiocarbamic acid 2-[4-(2-diethylthiocarbamoylsulfanyl-2-phenyl-acetyl)-2,5-dioxo-piperazin-1-yl]-2-oxo-1-phenyl-ethyl ester as new reversible addition-fragmentation chain transfer agent for polymerization of ethyl methacrylate

Abdollahi

Abdouss

Salami‐Kalajahi

et al. 2015

Designed Monomers and Polymers

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-Nezhad (2016) Synthesis and characterization of diethyl-dithiocarbamic acid 2-[4-(2-diethylthiocarbamoylsulfanyl-2-phenyl-acetyl)-2,5-dioxo-piperazin-1-yl]-2-oxo-1-phenyl-ethyl ester as new reversible addition-fragmentation chain transfer agent for polymerization of ethyl methacrylate, Designed Monomers and Polymers, 19:1, 56-66, DOI: 10.1080/15685551.2015 C NMR, FT-IR, elemental analysis, and melting point technique. Then, ethyl methacrylate was synthesized via free radical and RAFT polymerizations. To investigate the effect of the RAFT agent on the kinetic of polymerization, molecular weight, and polydispersity index (PDI) of polymers and also monomer conversion were monitored. Also, synthesized polymers were characterized by 1 H NMR, 13 C NMR, FT-IR, and TGA. Characterization analyses of synthesized RAFT agent were consistent with the structure. NMR and FTIR analyses confirmed end group incorporation of RAFT agent into polymer structure. According to results, poly(ethyl methacrylate) with low PDI (1.14) was obtained. Kinetic study indicated well-controlled polymerization of ethyl methacrylate by synthesized RAFT agent. TGA results showed that RAFT agent could reduce termination reactions and so reduce head-to-head bonds and chain-end unsaturation by keeping the concentration of radicals low enough.

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Drug solubilization by amino acid based polymeric nanoparticles: Characterization and biocompatibility studies

Cited by 31 publications

References 46 publications

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Synthesis and characterization of diethyl-dithiocarbamic acid 2-[4-(2-diethylthiocarbamoylsulfanyl-2-phenyl-acetyl)-2,5-dioxo-piperazin-1-yl]-2-oxo-1-phenyl-ethyl ester as new reversible addition-fragmentation chain transfer agent for polymerization of ethyl methacrylate

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Drug solubilization by amino acid based polymeric nanoparticles: Characterization and biocompatibility studies

Cited by 31 publications

References 46 publications

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Mixed nanomicelles as potential carriers for&nbsp;systemic delivery of Z-GP-Dox, an FAP&alpha;-based doxorubicin prodrug: formulation and pharmacokinetic evaluation

Synthesis and characterization of diethyl-dithiocarbamic acid 2-[4-(2-diethylthiocarbamoylsulfanyl-2-phenyl-acetyl)-2,5-dioxo-piperazin-1-yl]-2-oxo-1-phenyl-ethyl ester as new reversible addition-fragmentation chain transfer agent for polymerization of ethyl methacrylate

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Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an FAPα-based doxorubicin prodrug: formulation and pharmacokinetic evaluation