scholarly journals Fabrication of Polymer Micelles with Zwitterionic Shell and Biodegradable Core for Reductively Responsive Release of Doxorubicin

Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1019 ◽  
Author(s):  
Junting Jiang ◽  
Junbo Li ◽  
Biyu Zhou ◽  
Chaohuang Niu ◽  
Wendi Wang ◽  
...  
Keyword(s):  
Drug Release ◽  
Disulfide Bonds ◽  
High Stability ◽  
Polymeric Micelles ◽  
Raft Polymerization ◽  
Drug Efficacy ◽  
Low Protein ◽  
Self Assembling ◽  
Group Modification ◽  
End Group Modification

To achieve a high stability in physiological environment and rapid intracellular drug release, a biodegradable zwitterionic triblock copolymer with a disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCBMA-SS-PCL-SS-PCBMA) was prepared for micellar carrier to delivery doxorubicin (DOX) into tumor cells. PCBMA-SS-PCL-SS-PCBMA was obtained by following steps: i) introducing disulfide bonds through end-group modification of PCL diol with cystamine dihydrochloride; ii) preparing PCL-RAFT macromolecular chain transfer agent by EDC/NHS chemistry; iii) RAFT polymerization of zwitterionic monomer. Self-assembling from PCBMA-SS-PCL-SS-PCBMA, polymeric micelles had many advantages, such as ultra-low protein absorption in serum and obvious reduction-responsiveness in the presence of DTT. Furthermore, DOX-loaded micelles exhibited high stability upon centrifugation and lyophilization, a fast intracellular drug release and enhanced drug efficacy due to GSH-triggered PCBMA shell shedding and micellar reassembling. Thus, the polymeric micelles integrated several functions and properties could be prospectively utilized as valuable nanocarriers in cancer chemotherapeutics.

RAFT Polymer End-Group Modification and Chain Coupling/Conjugation Via Disulfide Bonds

2009 ◽  
Vol 62 (8) ◽  
pp. 830 ◽  
Author(s):  
Cyrille Boyer ◽  
Jingquan Liu ◽  
Volga Bulmus ◽  
Thomas P. Davis
Keyword(s):  
Disulfide Bonds ◽  
Diblock Copolymers ◽  
Raft Polymerization ◽  
Gel Permeation Chromatography ◽  
Reversible Addition ◽  
Group Modification ◽  
End Groups ◽  
End Group Modification ◽  
High Yields ◽  
End Group

End-group modification of polymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization was accomplished by the conversion of trithiocarbonate or dithioester end-groups into a pyridyl disulfide (PDS) functionality. Several different polymers, such as poly(methyl methacrylate), polystyrene, poly(oligoethylene glycol-acrylate), poly(hydroxypropylacrylamide), and poly(N-isopropylacrylamide) were prepared by RAFT polymerization, and subjected to aminolysis in the presence of 2,2′-dithiodipyridine to yield thiol-terminated polymers with yields in the range 65–90% dependent on the polymer structure. Furthermore, this PDS end-group was utilized to generate higher-order architectures, such as diblock copolymers with high yields and selectively. In addition, the PDS end-groups were used for the bioconjugation of different biomolecules, such as oligonucleotides, carbohydrates, and peptides. The successful modification of well-defined polymers was confirmed by a combination of UV-vis, NMR spectroscopy, and gel permeation chromatography.

Photoluminescent polymeric micelles from poly(ethylene oxide)-block-poly(((4-vinylphenyl)ethene-1,1,2-triyl)tribenzene) diblock copolymers

2018 ◽  
Vol 42 (9) ◽  
pp. 7283-7292 ◽  
Author(s):  
Muhammad Adeel ◽  
Sen Xu ◽  
Bingjie Zhao ◽  
Lei Li ◽  
Sixun Zheng
Keyword(s):  
Ethylene Oxide ◽  
Diblock Copolymers ◽  
Polymeric Micelles ◽  
Raft Polymerization ◽  
Aqueous Media ◽  
Self Assembling ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

We report the synthesis of poly(ethylene oxide)-block-poly(((4-vinylphenyl)ethene-1,1,2-triyl)tribenzene) diblock copolymers via RAFT polymerization. The diblock copolymers were capable of self-assembling into photoluminescent micelles in aqueous media.

scholarly journals Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1464
Author(s):  
Yang Yang ◽  
Fuwei Yang ◽  
Xiaotian Shan ◽  
Jiamin Xu ◽  
Wenjie Fang ◽  
...  
Keyword(s):  
Drug Release ◽  
Tumor Cells ◽  
Disulfide Bonds ◽  
Polymeric Micelles ◽  
Inhibitory Effect ◽  
In Vitro Drug Release ◽  
In Vivo Antitumor Activity ◽  
Ph Reduction

At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.

scholarly journals Effective End-Group Modification of Star-Shaped PNVCL from Xanthate to Trithiocarbonate Avoiding Chemical Crosslinking

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3677
Author(s):  
Norma A. Cortez-Lemus ◽  
Eduardo Hermosillo-Ochoa ◽  
Ángel Licea-Claverie
Keyword(s):  
Raft Polymerization ◽  
Benzyl Bromide ◽  
Star Polymers ◽  
Solution Concentration ◽  
Hydrodynamic Diameter ◽  
Reversible Addition ◽  
Yellow Color ◽  
Group Modification ◽  
End Group Modification ◽  
Responsive Behavior

In this study, six-arm star-shaped poly(N-vinylcaprolactam) (PNVCL) polymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization were subjected to aminolysis reaction using hexylamine. Chemically crosslinked gels or highly end-functionalized star polymers can be obtained depending mainly on the type of solvent used during the transformation of the RAFT functional group. An increase in the viscosity of the solution was observed when the aminolysis was carried out in THF. In contrast, when the reaction was conducted in dichloromethane, chain-end thiol (PNVCL)6 star polymers could be obtained. Moreover, when purified (PNVCL-SH)6 star polymers are in contact with THF, the gelation occurs in just a few minutes, with an obvious increase in viscosity, to form physical gels that become chemically crosslinked gels after 12 h. Interestingly, when purified (PNVCL-SH)6 star polymers were stirred in distilled water, even at high aqueous solution concentration (40 mg/mL), there was no increase in the viscosity or gelation, and no evident gels were observed. The analysis of the hydrodynamic diameter (Dh) by dynamic light scattering (DLS) did not detect quantifiable change even after 4 days of stirring in water. On the other hand, the thiol groups in the (PNVCL-SH)6 star polymers were easily transformed into trithiocarbonate groups by addition of CS2 followed by benzyl bromide as demonstrated by UV-Vis spectroscopical analysis and GPC. After the modification, the (PNVCL)6 star polymers exhibit an intense yellow color typical of the absorption band of trithiocarbonate group at 308 nm. To further demonstrate the highly effective new trithiocarbonate end-functionality, the PNVCL polymers were successfully chain extended with N-isopropylacrylamide (NIPAM) to form six-arm star-shaped PNIPAM-b-PNVCL block copolymers. Moreover, the terminal thiol end-functionality in the (PNVCL-SH)6 star polymers was linked via disulfide bond formation to l-cysteine to further demonstrate its reactivity. Zeta potential analysis shows the pH-responsive behavior of these star polymers due to l-cysteine end-functionalization. By this using methodology and properly selecting the solvent, various environment-sensitive star polymers with different end-groups could be easily accessible.

scholarly journals Combining Dextran Conjugates with Stimuli-Responsive and Folate-Targeting Activity: A New Class of Multifunctional Nanoparticles for Cancer Therapy

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1108
Author(s):  
Manuela Curcio ◽  
Alessandro Paolì ◽  
Giuseppe Cirillo ◽  
Sebastiano Di Pietro ◽  
Martina Forestiero ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Release ◽  
Metastatic Cancer ◽  
Stimuli Responsive ◽  
Cancer Disease ◽  
New Class ◽  
Self Assembling ◽  
Redox Responsive ◽  
Potential Applicability ◽  
Mean Size

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for folate receptors were prepared by the combination of two amphiphilic dextran (DEX) derivatives. DEXFA conjugate was obtained by covalent coupling of the polysaccharide with folic acid (FA), whereas DEXssPEGCOOH derived from a reductive amination step of DEX was followed by condensation with polyethylene glycol 600. After self-assembling, nanoparticles with a mean size of 50 nm, able to be destabilized in acidic pH and reducing media, were obtained. Doxorubicin was loaded during the self-assembling process, and the release experiments showed the ability of the proposed system to modulate the drug release in response to different pH and redox conditions. Finally, the viability and uptake experiments on healthy (MCF-10A) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a new drug vector in cancer therapy.

scholarly journals Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 744
Author(s):  
Ijeoma F. Uchegbu ◽  
Jan Breznikar ◽  
Alessandra Zaffalon ◽  
Uche Odunze ◽  
Andreas G. Schätzlein
Keyword(s):  
Polymeric Micelles ◽  
Rabbit Model ◽  
Penetration Enhancer ◽  
Hydrophobic Drugs ◽  
Ocular Tissues ◽  
Ocular Penetration ◽  
Self Assembling ◽  
Similar Dose ◽  
Oil In Water ◽  
The Stability

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/v CsA and 0.375–0.75% w/v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC0–24 levels were 25,780 ng.h g−1, 12,046 ng.h g−1 and 5879 ng.h g−1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.

Polymeric micelles using cholinium-based ionic liquids for the encapsulation and drug release of hydrophobic molecules

2021 ◽  
Author(s):  
Isabelle Kurnik ◽  
Natália D’Angelo ◽  
Priscila Gava Mazzola ◽  
Marlus Chorilli ◽  
Daniel Kamei ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
Drug Release ◽  
Polymeric Micelles ◽  
Amphiphilic Copolymer ◽  
Two Phase ◽  
Temperature Responsive ◽  
Micellar Systems

We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic® L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The...

scholarly journals Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 377
Author(s):  
Kyoung Nan Kim ◽  
Keun Sang Oh ◽  
Jiwook Shim ◽  
Isabel R. Schlaepfer ◽  
Sana D. Karam ◽  
...  
Keyword(s):  
High Stability ◽  
Polymeric Micelles ◽  
Uv Light ◽  
Cancer Drug ◽  
Stacking Interactions ◽  
Anti Cancer ◽  
Target Sites ◽  
Formulation Stability ◽  
Micellar Core ◽  
Micellar Nanoparticles

Light-sensitive polymeric micelles have recently emerged as promising drug delivery systems for spatiotemporally controlled release of payload at target sites. Here, we developed diazonaphthoquinone (DNQ)-conjugated micellar nanoparticles that showed a change in polarity of the micellar core from hydrophobic to hydrophilic under UV light, releasing the encapsulated anti-cancer drug, doxetaxel (DTX). The micelles exhibited a low critical micelle concentration and high stability in the presence of bovine serum albumin (BSA) solution due to the hydrophobic and π–π stacking interactions in the micellar core. Cell studies showed enhanced cytotoxicity of DTX-loaded micellar nanoparticles upon irradiation. The enhanced stability would increase the circulation time of the micellar nanoparticles in blood, and enhance the therapeutic effectiveness for cancer therapy.

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