179388-73-9Relevant articles and documents
Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice
Dutta, Rinku,Kumar, Virender,Peng, Yang,Evande, Ruby E.,Grem, Jean L.,Mahato, Ram I.
, p. 564 - 578 (2017)
Purposes: To determine the pharmacokinetic parameters and biodistribution of GDC-0449 loaded polymeric micelles after systemic administration into common bile duct ligation (CBDL) induced liver fibrotic mice. Methods: We used GDC-0449 encapsulated methoxy
Synthesis and liquid crystal behavior of new side chain aliphatic polycarbonates based on cholesterol
Liu, Xiaofeng,Guo, Zhihao,Xie, Yujiao,Chen, Zhangpei,Hu, Jianshe,Yang, Liqun
, p. 350 - 358 (2018)
In this study, we synthesized a series of new liquid crystal aliphatic block polycarbonates copolymers mPEG43-b-P(MCC-Cn)51 (n = 1–4) via the ring-opening polymerization, hydrogenation reduction and coupling reaction, which contained side functionalized cholesteryl groups and were different in the number of the flexible methylene groups. The chemical structures of the chiral compounds and copolymers obtained in this study were characterized by FT-IR and 1H NMR spectra, and the average molecular weights of the copolymers were investigated by average molecular weights gel permeation chromatographic (GPC). The polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to characterize the liquid crystal behavior. The relationship of the structure and phase behavior of the chiral compounds and copolymers influenced by spacer lengths was discussed. As a result, the chiral compounds with two methylene only showed a smectic A (SmA) phase, while those with more methylene showed a SmA phase and cholesteric phase. As the number of the flexible methylene groups increased, the corresponding melting temperature, the transition temperatures of LC phases and the isotropic temperature of chiral compounds all showed a decreasing trend, and mesophase temperature range narrowed. The polycarbonate copolymer with two methylene did not show mesomorphism, while the copolymers with longer spacer length seemed beneficial for the formation of mesophases at room temperature and revealed a smectic A phase with an interdigitated molecular arrangement on heating and cooling cycles. The results showed a decreased tendency toward the glass temperature, and an increased tendency toward isotropic temperature for the LC copolymers with an increase of the spacer length.
Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus
Wang, Menglin,Sun, Jin,Zhai, Yinglei,Lian, He,Luo, Cong,Li, Lin,Du, Yuqian,Zhang, Dong,Ding, Wenya,Qiu, Shuhong,Liu, Yuhai,Kou, Longfa,Han, Xiangfei,Xiang, Rongwu,Wang, Yongjun,He, Zhonggui
, p. 1179 - 1190 (2015)
(Figure Presented) To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)-poly(2-methyl-2-carboxyl-propylene carbonate)-vitamin E, mPEG-PCC-VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113-PCC32-VE4 exhibited low critical micelle concentration of 1.7 × 10-6 mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113-PCC32-VE4 micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.
Synthesis and characterization of hyperbranched poly(ε-caprolactone)s having different lengths of homologous backbone segments
Choi, Jeongsoo,Kwak, Seung-Yeop
, p. 8630 - 8637 (2003)
Hyperbranched poly(ε-caprolactone)s (HPCLs) were synthesized by moisture-sensitive catalyst-free polycondensation of AB2 macromonomers, 2,2-bis[ω-hydroxy oligo(ε-caprolactone)methyl]-propionic acids. The HPCLs were designed to incorporate diffe
Cholesterol and Morpholine Grafted Cationic Amphiphilic Copolymers for miRNA-34a Delivery
Sharma, Saurabh,Mazumdar, Samrat,Italiya, Kishan S.,Date, Tushar,Mahato, Ram I.,Mittal, Anupama,Chitkara, Deepak
, p. 2391 - 2402 (2018)
miR-34a is a master tumor suppressor playing a key role in the several signaling mechanisms involved in cancer. However, its delivery to the cancer cells is the bottleneck in its clinical translation. Herein we report cationic amphiphilic copolymers graft
Lactic acid- and carbonate-based crosslinked polymeric micelles for drug delivery
Danquah, Michael,Fujiwara, Tomoko,Mahato, Ram I.
, p. 347 - 362 (2013)
Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co- lactide-co-5-methyl-5-allyloxycarbo
Sensitization of LnIII (Ln = Eu, Tb, Tm) Ion Luminescence by Functionalized Polycarbonate-Based Materials and White Light Generation
Tigaa, Rodney A.,Aerken, Xuekelaiti,Fuchs, Alan,de Bettencourt-Dias, Ana
, p. 5310 - 5317 (2017)
We prepared pyridine-2,6-bis(ethyl)ester [BEP] and pyridine-2,6-bis(diethylamide) [BDP] polymers with polycarbonate backbones by ring-opening polymerization of the pyridine-bis(ethyl)ester and pyridine-bis(diethylamide) units appended to a cyclic carbonat
EGFR-Targeted Cationic Polymeric Mixed Micelles for Codelivery of Gemcitabine and miR-205 for Treating Advanced Pancreatic Cancer
Mondal, Goutam,Almawash, Saud,Chaudhary, Amit Kumar,Mahato, Ram I.
, p. 3121 - 3133 (2017)
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy. Cetuximab C225 was conjugated to malemido-poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol (C225-PEG-PCD) to prepare mixed micelles with mPEG-b-PCC-g-GEM-g-DC-g-TEPA for targeted codelivery of GEM and miR-205. This mixed micelle formulation showed a significant enhancement in EGFR-mediated cellular uptake in GEM-resistant MIA PaCa-2R cells. Further, an enhanced tumor accumulation of C225-micelles conjugated with near-infrared fluorescent Cy7.5 dye and Dy677-labeled miR-205 in orthotopic pancreatic tumor bearing NSG mice was evident after systemic administration. In addition, inhibition of tumor growth was also observed with increased apoptosis and reduced EMT after treatment with C225-micelles containing GEM and miR-205. Therefore, we believe that the targeted delivery of GEM and miR-205 in combination could be a novel strategy for treating advanced pancreatic cancer.
Biodegradable broad-spectrum antimicrobial polycarbonates: Investigating the role of chemical structure on activity and selectivity
Chin, Willy,Yang, Chuan,Ng, Victor Wee Lin,Huang, Yuan,Cheng, Junchi,Tong, Yen Wah,Coady, Daniel J.,Fan, Weimin,Hedrick, James L.,Yang, Yi Yan
, p. 8797 - 8807 (2013)
A series of biodegradable polycarbonate polymers was designed and synthesized via organocatalytic ring-opening polymerization of functional cyclic carbonate monomer (MTC-OCH2BnCl). By adopting a facile postpolymerization functionalization strategy, the polycarbonates were quaternized to yield cationic polymers with quaternary ammonium groups of various pendant structures (e.g., alkyl, aromatic, imidazolinium). The biological properties of these polymers were investigated by microbial growth inhibition assays against clinically relevant Gram-positive and Gram-negative bacteria, fungus as well as hemolysis assays using rat red blood cells. A judicious choice in the structure of the cationic appendages elucidated that the amphiphilic balance of the polymers is a pertinent determinant to render substantial antimicrobial potency and low hemolysis, consequently affording the polymer pButyl-20 (degree of polymerization, 20; quaternary ammonium group, N,N-dimethylbutylammonium) as a highly efficacious and nonhemolytic antimicrobial agent with a remarkable selectivity of more than 1026. To ameliorate the selectivity against a wider spectrum of microbes including the difficult-to-kill Pseudomonas aeruginosa, it was shown that polymers containing N,N-dimethylbutylammonium and N,N-dimethylbenzylammonium groups in 1:1 molar ratio exerted considerable antimicrobial potency while remaining relatively nonhemolytic. Biophysical studies encompassing the determination of water-octanol partition coefficients (log P) and dye leakage studies from model liposomes provided useful insights which delineate the pivotal role of cationic group structure in the antimicrobial activity and mechanism of these polymers. Through field emission scanning electron microscopy (FE-SEM), a physical lysis of microbial cell membranes was deemed operative in the antimicrobial action of these macromolecular agents, which would consequently reduce the propensity toward resistance development. These polymers are envisaged to be promising antimicrobial agents for the prevention and treatment of multidrug-resistant pathogenic infections.
Construction of Janus dendrimers through a self-assembly approach involving chiral discrimination at a focal point
Cole, Ashley M.,Kilway, Kathleen V.,Menuey, Elizabeth M.,Moteki, Shin A.,Zhou, John
supporting information, p. 6404 - 6407 (2021/07/02)
A strategy to build Janus dendrimersviathe chirality-directed self-assembly of heteroleptic Zn(ii) BOX complexes is reported. The method allows quantitative synthesis of Janus dendrimersin situwithout the need for purifications. Each dendritic domain of t
Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms
Garciá-Gallego, Sandra,Stenstr?m, Patrik,Mesa-Antunez, Pablo,Zhang, Yuning,Malkoch, Michael
, p. 4273 - 4279 (2020/11/09)
Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weig
