Self-Assembly of Partially Alkylated Dextran-<i>graft</i>-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties

Chandel, Arvind K. Singh; Nutan, Bhingaradiya; Raval, Ishan H.; Jewrajka, Suresh K.

doi:10.1021/acs.biomac.8b00015

Cited by 71 publications

(88 citation statements)

References 66 publications

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“…Small hydrophilic molecules are widely used for treating diseases such as infectious diseases (Macielag, 2012;Zhang et al, 2015;Chandel et al, 2018), cancer (Xu et al, 2014;Zhao et al, 2016), and local anesthesia (Howell and Chauhan, 2009;Jug et al, 2010). Although effective, the dosage, therapeutic effect, and patient accomplishment of such compounds are usually limited by the tendency to distribute into the biological aqueous environment of the human body, leading to side effects (Weiniger et al, 2010;Wang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules

Zhao

2020

Front. Bioeng. Biotechnol.

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The therapeutic effect of small hydrophilic molecules is limited by the rapid clearance from the systemic circulation or a local site of administration. The unsuitable pharmacokinetics and biodistribution can be improved by encapsulating them in drug delivery systems. However, the high-water solubility, very hydrophilic nature, and low molecular weight make it difficult to encapsulate small hydrophilic molecules in many drug delivery systems. In this mini-review, we highlight three strategies to efficiently encapsulate small hydrophilic molecules and achieve controlled release: physical encapsulation in micro/nanocapsules, physical adsorption via electronic interactions, and covalent conjugation. The principles, advantages, and disadvantages of each strategy are discussed. This review paper could be a guide for scientists, engineers, and medical doctors who want to improve the therapeutic efficacy of small hydrophilic drugs.

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Section: Introductionmentioning

confidence: 99%

Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules

Zhao

2020

Front. Bioeng. Biotechnol.

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“…For example, a cleavable crosslinker affords a stimuli-responsive degradability [9][10][11], and a crosslinking point with dynamic covalent bond can undergo structure reorganization by stimulus [12,13]. In addition, a polymeric crosslinker gives an amphiphilic network structure having unique swelling property in both of water and organic solvents [14][15][16][17][18][19]. Despite of these examples, the fundamental research on the effect of a crosslinker on gel properties is still limited particularly in the general synthetic method of vinyl polymer gels probably due to the poor structural diversity particularly in the general synthetic method of vinyl polymer gels probably due to the poor structural diversity of a crosslinker, a divinyl compound.…”

Section: Introductionmentioning

confidence: 99%

Crosslinker-Based Regulation of Swelling Behavior of Poly(N-isopropylacrylamide) Gels in a Post-Polymerization Crosslinking System

Ida

Katsurada

Tsujio

et al. 2019

Gels

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A fundamental understanding of the effect of a crosslinker on gel properties is important for the design of novel soft materials because a crosslinking is a key component of polymer gels. We focused on post-polymerization crosslinking (PPC) system utilizing activated ester chemistry, which is a powerful tool due to structural diversity of diamine crosslinkers and less susceptibility to solvent effect compared to conventional divinyl crosslinking system, to systematically evaluate the crosslinker effect on the gel properties. A variety of alkyldiamine crosslinkers was employed for the synthesis of poly(N-isopropylacrylamide) (PNIPAAm) gels and it was clarified that the length of alkyl chains of diamine crosslinkers strongly affected the gelation reaction and the swelling behavior. The longer crosslinker induced faster gelation and decreased the swelling degree and the response temperature in water, while the crosslinking density did not significantly change. In addition, we were able to modify the polymer chains in parallel with crosslinking by using a monoamine modifier along with a diamine crosslinker. This simultaneous chain modification during crosslinking (SMC) was demonstrated to be useful for the regulation of the crosslinking density and the swelling behavior of PNIPAAm gels.Gels 2020, 6, 2 2 of 10 of a crosslinker, a divinyl compound. Free radical polymerization of a monomer in the presence of a crosslinker is a simple and important method for the preparation of functional gels but, when focusing on a crosslinker, the design of a divinyl compound often requires a bothersome synthetic procedure. In addition, divinyl crosslinking reaction is susceptible to the reaction solvents and produce the different network structure depending on the solvent even if using a same monomer/crosslinker combination [20]. This strong solvent effect on the reaction leads to the difficulty in the understanding the effect of a crosslinkers on gel properties even at simply changing the alkyl chain length of a crosslinker, because the solubility of a crosslinker also affects the reaction particularly in the case of a hydrogel prepared in water. As a result, the influence of the crosslinking agent on the gel has been difficult to be investigated so far in spite of the importance in gel properties [21].We are focusing on a gel synthesis by post-polymerization crosslinking (PPC) system in which prepolymers having activated ester moieties are reacted with a diamine compound as a crosslinker (Scheme 1a) [22][23][24][25][26]. This method is performed by simply mixing a prepolymer with a crosslinker, and it is possible to diversely change the gel structure by an appropriate design of the prepolymer. For example, simple mixing two kinds of poly(acrylamide derivative) prepolymers with different solubility afforded an amphiphilic co-network structure showing unique thermoresponsive swelling behavior [24]. In addition, a designed amphiphilic structure with crosslinked domains can be obtained by using the triblock prepolymer having reactive s...

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“…Among these efforts, introduction of micelles, which undergo microscopic phase separation in aqueous environment, could consume the external loading to impart the hydrogels with higher resistance under big strain . Most importantly, the micelles also can work as carriers of biomolecules to realize controlled release, so to improve regeneration effect …”

Section: Introductionmentioning

confidence: 99%

Poly(l‐glutamic acid)‐based micellar hydrogel with improved mechanical performance and proteins loading

Zhang

Kong

Yin

2019

J Polym Sci B Polym Phys

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Soft tissues, such as fat and skin, present high flexibility and are capable of withstanding large deformation in various functions. Hydrogels that can resemble the mechanical performance of soft tissue are unique and widely demanded. In this study, micellar hydrogels based on biocompatible poly(l‐glutamic acid) (PLGA) were designed with the enhanced capacity to bear large deformation. Amphipathic triblock copolymer poly(ethylene glycol) acrylate‐co‐poly(ε‐caprolactone)‐co‐poly (ethylene glycol) acrylate (APEG‐PCL‐APEG) with two terminal double bonds was synthesized and self‐assembled into micelles. At the same time, graft copolymers, poly(l‐glutamic acid)‐g‐hydroxyethyl methacrylate (PLGA‐g‐HEMA) with double bonds were synthesized. APEG‐PCL‐APEG micelles and PLGA‐g‐HEMA were mixed to construct micellar hydrogel via radical polymerization. The crystalline structure and hydrophobic aggregation of copolymers (APEG‐PCL‐APEG) were found to associate with PCL molecular weight. Due to the hydrophobic stress dissipation and crystalline structure of the micelles, the softness and toughness of hydrogels were promoted, exhibiting a 25% increase in ultimate strain. Moreover, the micellar hydrogels were able to load proteins with long‐term retention. In addition, under dynamic mechanical stimulation, the release of proteins could be accelerated. Besides, the micellar hydrogels also supported rabbit adipose‐derived stem cells (rASCs) growth, thus exhibiting the potential toward soft tissue engineering. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 1115–1125

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Self-Assembly of Partially Alkylated Dextran-graft-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties

Cited by 71 publications

References 66 publications

Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules

Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules

Crosslinker-Based Regulation of Swelling Behavior of Poly(N-isopropylacrylamide) Gels in a Post-Polymerization Crosslinking System

Poly(l‐glutamic acid)‐based micellar hydrogel with improved mechanical performance and proteins loading

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