Research

15 pages, 4490 KiB

Open AccessArticle

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

by Abegaz Tizazu Andrgie, Yihenew Simegniew Birhan, Tefera Worku Mekonnen, Endiries Yibru Hanurry, Haile Fentahun Darge, Rong-Ho Lee, Hsiao-Ying Chou and Hsieh-Chih Tsai

Polymers 2020, 12(1), 43; https://doi.org/10.3390/polym12010043 - 27 Dec 2019

Cited by 20 | Viewed by 3551

Abstract

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing [...] Read more.

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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16 pages, 3925 KiB

Open AccessArticle

Synthesis and Self-Assembly of Multistimulus-Responsive Azobenzene-Containing Diblock Copolymer through RAFT Polymerization

by Po-Chih Yang, Yueh-Han Chien, Shih-Hsuan Tseng, Chia-Chung Lin and Kai-Yu Huang

Polymers 2019, 11(12), 2028; https://doi.org/10.3390/polym11122028 - 06 Dec 2019

Cited by 2 | Viewed by 3622

Abstract

This paper gathered studies on multistimulus-responsive sensing and self-assembly behavior of a novel amphiphilic diblock copolymer through a two-step reverse addition-fragmentation transfer (RAFT) polymerization technique. N-Isopropylacrylamide (NIPAM) macromolecular chain transfer agent and diblock copolymer (poly(NIPAM-b-Azo)) were discovered to have moderate [...] Read more.

This paper gathered studies on multistimulus-responsive sensing and self-assembly behavior of a novel amphiphilic diblock copolymer through a two-step reverse addition-fragmentation transfer (RAFT) polymerization technique. N-Isopropylacrylamide (NIPAM) macromolecular chain transfer agent and diblock copolymer (poly(NIPAM-b-Azo)) were discovered to have moderate thermal decomposition temperatures of 351.8 and 370.8 °C, respectively, indicating that their thermal stability was enhanced because of the azobenzene segments incorporated into the block copolymer. The diblock copolymer was determined to exhibit a lower critical solution temperature of 34.4 °C. Poly(NIPAM-b-Azo) demonstrated a higher photoisomerization rate constant (k_t = 0.1295 s⁻¹) than the Azo monomer did (k_t = 0.088 s⁻¹). When ultraviolet (UV) irradiation was applied, the intensity of fluorescence gradually increased, suggesting that UV irradiation enhanced the fluorescence of self-assembled cis-isomers of azobenzene. Morphological aggregates before and after UV irradiation are shown in scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses of the diblock copolymer. We employed photoluminescence titrations to reveal that the diblock copolymer was highly sensitive toward Ru³⁺ and Ba²⁺, as was indicated by the crown ether acting as a recognition moiety between azobenzene units. Micellar aggregates were formed in the polymer aqueous solution through dissolution; their mean diameters were approximately 205.8 and 364.6 nm at temperatures of 25.0 and 40.0 °C, respectively. Our findings contribute to research on photoresponsive and chemosensory polymer material developments. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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16 pages, 3183 KiB

Open AccessEditor’s ChoiceArticle

Dual-Wavelength (UV and Blue) Controlled Photopolymerization Confinement for 3D-Printing: Modeling and Analysis of Measurements

by Jui-Teng Lin, Da-Chuan Cheng, Kuo-Ti Chen and Hsia-Wei Liu

Polymers 2019, 11(11), 1819; https://doi.org/10.3390/polym11111819 - 06 Nov 2019

Cited by 25 | Viewed by 4386

Abstract

The kinetics and modeling of dual-wavelength (UV and blue) controlled photopolymerization confinement (PC) are presented and measured data are analyzed by analytic formulas and numerical data. The UV-light initiated inhibition effect is strongly monomer-dependent due to different C=C bond rate constants and conversion [...] Read more.

The kinetics and modeling of dual-wavelength (UV and blue) controlled photopolymerization confinement (PC) are presented and measured data are analyzed by analytic formulas and numerical data. The UV-light initiated inhibition effect is strongly monomer-dependent due to different C=C bond rate constants and conversion efficacies. Without the UV-light, for a given blue-light intensity, higher initiator concentration (C₁₀) and rate constant (k’) lead to higher conversion, as also predicted by analytic formulas, in which the total conversion rate (R_T) is an increasing function of C₁ and k’R, which is proportional to k’[gB₁C₁]^0.5. However, the coupling factor B₁ plays a different role that higher B₁ leads to higher conversion only in the transient regime; whereas higher B₁ leads to lower steady-state conversion. For a fixed initiator concentration C₁₀, higher inhibitor concentration (C₂₀) leads to lower conversion due to a stronger inhibition effect. However, same conversion reduction was found for the same H-factor defined by H₀ = [b₁C₁₀ − b₂C₂₀]. Conversion of blue-only are much higher than that of UV-only and UV-blue combined, in which high C₂₀ results a strong reduction of blue-only-conversion, such that the UV-light serves as the turn-off (trigger) mechanism for the purpose of spatial confirmation within the overlap area of UV and blue light. For example, UV-light controlled methacrylate conversion of a glycidyl dimethacrylate resin is formulated with a tertiary amine co-initiator, and butyl nitrite. The system is subject to a continuous exposure of a blue light, but an on-off exposure of a UV-light. Finally, we developed a theoretical new finding for the criterion of a good material/candidate governed by a double ratio of light-intensity and concentration, [I₂₀C₂₀]/[I₁₀C₁₀]. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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15 pages, 6559 KiB

Open AccessArticle

Tunable Thermo-Responsive Copolymers from DEGMA and OEGMA Synthesized by RAFT Polymerization and the Effect of the Concentration and Saline Phosphate Buffer on Its Phase Transition

by Alejandro Ramírez-Jiménez, Kathleen Abigail Montoya-Villegas, Angel Licea-Claverie and Mirian Angelene Gónzalez-Ayón

Polymers 2019, 11(10), 1657; https://doi.org/10.3390/polym11101657 - 11 Oct 2019

Cited by 29 | Viewed by 5405

Abstract

Thermo-responsive polymers and copolymers derivatives of oligo(ethylene glycol) methyl ether methacrylate (M_n = 300 g mol⁻¹) (OEGMA) and di(ethylene glycol) methyl ether methacrylate (DEGMA) have been synthesized by reversible addition fragmentation chain transfer polymerization (RAFT) using 5-amino-4-methyl-4-(propylthiocarbonothioylthio)-5-oxopentanoic acid (APP) [...] Read more.

Thermo-responsive polymers and copolymers derivatives of oligo(ethylene glycol) methyl ether methacrylate (M_n = 300 g mol⁻¹) (OEGMA) and di(ethylene glycol) methyl ether methacrylate (DEGMA) have been synthesized by reversible addition fragmentation chain transfer polymerization (RAFT) using 5-amino-4-methyl-4-(propylthiocarbonothioylthio)-5-oxopentanoic acid (APP) as chain transfer agent (CTA). The monomer conversion was evaluated by hydrogen nuclear magnetic resonance (¹H-NMR); number average molecular weights (M_n), weight average molecular weight (M_w), and dispersity (Đ) were obtained by gel permeation chromatography (GPC); glass transition temperature (T_g) was evaluated by modulated differential scanning calorimetry (DSC), cloud point temperature (Tcp) was measured and compared by turbidimetry and dynamic light scattering (DLS). The effect of polymer composition and concentration on the Tcp, either in water or in phosphate buffer saline (PBS), was studied. The values of Tcp using PBS were between 3 and 4 °C lower than using water. Results showed an ideal copolymerization behavior; therefore, the Tcp could be tuned by an adequate monomers feed ratio obtaining polymers which may be used in drug delivery and other applications. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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17 pages, 4910 KiB

Open AccessArticle

Thiol–Ene Photopolymerization: Scaling Law and Analytical Formulas for Conversion Based on Kinetic Rate and Thiol–Ene Molar Ratio

by Kuo-Ti Chen, Da-Chuan Cheng, Jui-Teng Lin and Hsia-Wei Liu

Polymers 2019, 11(10), 1640; https://doi.org/10.3390/polym11101640 - 10 Oct 2019

Cited by 13 | Viewed by 2911

Abstract

Kinetics and analytical formulas for radical-mediated thiol–ene photopolymerization were developed in this paper. The conversion efficacy of thiol–ene systems was studied for various propagation to chain transfer kinetic rate-ratio (R_K), and thiol–ene concentration molar-ratio (R_C). Numerical data were analyzed [...] Read more.

Kinetics and analytical formulas for radical-mediated thiol–ene photopolymerization were developed in this paper. The conversion efficacy of thiol–ene systems was studied for various propagation to chain transfer kinetic rate-ratio (R_K), and thiol–ene concentration molar-ratio (R_C). Numerical data were analyzed using analytical formulas and compared with the experimental data. We demonstrated that our model for a thiol–acrylate system with homopolymerization effects, and for a thiol–norbornene system with viscosity effects, fit much better with the measured data than a previous model excluding these effects. The general features for the roles of R_K and R_C on the conversion efficacy of thiol (C_T) and ene (C_V) are: (i) for R_K = 1, C_V and C_T have the same temporal profiles, but have a reversed dependence on R_C; (ii) for R_K >> 1, C_T are almost independent of R_C; (iii) for R_K << 1, C_V and C_T have the same profiles and both are decreasing functions of the homopolymerization effects defined by k_CV; (iv) viscosity does not affect the efficacy in the case of R_K >> 1, but reduces the efficacy of C_V for other values of R_K. For a fixed light dose, higher light intensity has a higher transient efficacy but a lower steady-state conversion, resulting from a bimolecular termination. In contrast, in type II unimolecular termination, the conversion is mainly governed by the light dose rather than its intensity. For optically thick polymers, the light intensity increases with time due to photoinitiator depletion, and thus the assumption of constant photoinitiator concentration (as in most previous models) suffers an error of 5% to 20% (underestimated) of the crosslink depth and the efficacy. Scaling law for the overall reaction order, defined by [A]^m[B]ⁿ and governed by the types of ene and the rate ratio is discussed herein. The dual ratio (R_K and R_C) for various binary functional groups (thiol–vinyl, thiol–acrylate, and thiol–norbornene) may be tailored to minimize side effects for maximal monomer conversion or tunable degree of crosslinking. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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10 pages, 5273 KiB

Open AccessArticle

Preparation of Immunotherapy Liposomal-Loaded Thermal-Responsive Hydrogel Carrier in the Local Treatment of Breast Cancer

by Hsieh-Chih Tsai, Hsiao-Ying Chou, Shun-Hao Chuang, Juin-Yih Lai, Yi-Shu Chen, Yu-Han Wen, Lu-Yi Yu and Chun-Liang Lo

Polymers 2019, 11(10), 1592; https://doi.org/10.3390/polym11101592 - 29 Sep 2019

Cited by 14 | Viewed by 3124

Abstract

To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug [...] Read more.

To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug was released from the carrier, which could be a result of the morphological changes of the liposomal microstructure in the acidic environment. According to the results in animals, the drug-containing liposomes combined with hydrogel can be effectively applied in breast cancer therapy to delay the growth of tumors as well as to dramatically reduce the death rate of mice. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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18 pages, 3392 KiB

Open AccessArticle

Preparation of a Series of Photoresponsive Polymersomes Bearing Photocleavable a 2-nitrobenzyl Group at the Hydrophobic/Hydrophilic Interfaces and Their Payload Releasing Behaviors

by Shota Yamamoto, Takafumi Yamada, Genki Kubo, Kazuo Sakurai, Kazuo Yamaguchi and Jun Nakanishi

Polymers 2019, 11(8), 1254; https://doi.org/10.3390/polym11081254 - 29 Jul 2019

Cited by 9 | Viewed by 4433

Abstract

In this study, the structure-function relationships of a series of polymersomes composed of well-defined amphiphilic diblock copolymers were investigated. The building blocks were synthesized by clicking hydrophobic polymers, synthesized beforehand, and commercially available poly(ethylene glycol) with photocleavable 2-nitrobenzyl compounds bearing alkyne and maleimide [...] Read more.

In this study, the structure-function relationships of a series of polymersomes composed of well-defined amphiphilic diblock copolymers were investigated. The building blocks were synthesized by clicking hydrophobic polymers, synthesized beforehand, and commercially available poly(ethylene glycol) with photocleavable 2-nitrobenzyl compounds bearing alkyne and maleimide functionalities. All of the tested polymersomes preserved their hollow structures even after sufficient photoirradiation. Nevertheless, the release rate of an entrapped anionic fluorophore was highly dependent on the molecular weight and the type of hydrophobic polymer, as well as on the presence or absence of the charged end groups. Moreover, the polymersomes with a 2-nitrosobenzyl photolysis residue within the hydrophobic shells exhibited photo-induced payload release after complete photolysis. It was concluded that the payload release was mediated by photo-induced permeability changes of the hydrophobic shells rather than the decomposition of their overall structures. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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13 pages, 3906 KiB

Open AccessArticle

ZnO Quantum Dots Modified by pH-Activated Charge-Reversal Polymer for Tumor Targeted Drug Delivery

by Yifan Wang, Liang He, Bing Yu, Yang Chen, Youqing Shen and Hailin Cong

Polymers 2018, 10(11), 1272; https://doi.org/10.3390/polym10111272 - 15 Nov 2018

Cited by 37 | Viewed by 5890

Abstract

In this paper, we reported a pH responsive nano drug delivery system (NDDS) based on ZnO quantum dots (QDs) for controlled release of drugs. Zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) were introduced to modify ZnO QDs, which can help enhance [...] Read more.

In this paper, we reported a pH responsive nano drug delivery system (NDDS) based on ZnO quantum dots (QDs) for controlled release of drugs. Zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) were introduced to modify ZnO QDs, which can help enhance water stability, increase blood circulation time, and promote endocytosis. After tuning of PCBMA/PDMAEMA ratios, the ZnO@P(CBMA-co-DMAEMA) nanoplatform shows a sensitive switch from strong protein adsorption resistance (with negatively charged surface) at physiological pH to strong adhesion to tumor cell membranes (with positively charged surface) at the slightly acidic extracellular pH of tumors. Anti-cancer drug, Doxorubicin (DOX), molecules were demonstrated to be successfully loaded to ZnO@P(CBMA-co-DMAEMA) with a relatively large drug loading content (24.6%). In addition, ZnO@P(CBMA-co-DMAEMA) loaded with DOX can achieve lysosomal acid degradation and release of DOX after endocytosis by tumor cells, resulting in synergistic treatment of cancer, which is attributed to a combination of the anticancer effect of Zn²⁺ and DOX. Full article

(This article belongs to the Special Issue Functionally Responsive Polymeric Materials II)

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