RESUMEN
We present an approach for the rational development of stimuli-responsive ionogels which can be formulated for precise control of multiple unique ionogel features and fill niche pharmaceutical applications. Ionogels are captivating materials, exhibiting self-healing characteristics, tunable mechanical and structural properties, high thermal stability, and electroconductivity. However, the majority of ionogels developed require complex chemistry, exhibit high viscosity, poor biocompatibility, and low biodegradability. In our work, we overcome these limitations. We employ a facile production process and strategically integrate silk fibroin, the biocompatible ionic liquids (ILs) choline acetate ([Cho][OAc]), choline dihydrogen phosphate ([Cho][DHP]), and choline chloride ([Cho][Cl]), traditional pharmaceutical excipients, and the model antiepileptic drug phenobarbital. In the absence of ILs, we failed to observe gel formation; yet in the presence of ILs, thermoresponsive ionogels formed. Systems were assessed via visual tests, transmission electron microscopy, confocal reflection microscopy, dynamic light scattering, zeta potential and rheology measurements. We formed diverse ionogels of strengths ranging between 18 and 642 Pa. Under 25 °C storage, formulations containing polyvinylpyrrolidone (PVP) showed an ionogel formation period ranging over 14 days, increasing in the order of [Cho][DHP], [Cho][OAc], and [Cho][Cl]. Formulations lacking PVP showed an ionogel formation period ranging over 32 days, increasing in the order of [Cho][OAc], [Cho][DHP] and [Cho][Cl]. By heating from 25 to 60 °C, immediately following preparation, thermoresponsive ionogels formed below 41 °C in the absence of PVP. Based on our experimental results and density functional theory calculations, we attribute ionogel formation to macromolecular crowding and confinement effects, further enhanced upon PVP inclusion. Holistically, applying our rational development strategy enables the production of ionogels of tunable physicochemical and rheological properties, enhanced drug solubility, and structural and energetic stability. We believe our rational development approach will advance the design of biomaterials and smart platforms for diverse drug delivery applications.
RESUMEN
Thermoresponsive polymers with the appropriate structure form physical networks upon changes in temperature, and they find utility in formulation science, tissue engineering, and drug delivery. Here, we report a cost-effective biocompatible alternative, namely OEGMA30015-b-BuMA26-b-DEGMA13, which forms gels at low concentrations (as low as 2% w/w); OEGMA300, BuMA, and DEGMA stand for oligo(ethylene glycol) methyl ether methacrylate (MM = 300 g mol-1), n-butyl methacrylate, and di(ethylene glycol) methyl ether methacrylate, respectively. This polymer is investigated in depth and is compared to its commercially available counterpart, Poloxamer P407 (Pluronic F127). To elucidate the differences in their macroscale gelling behavior, we investigate their nanoscale self-assembly by means of small-angle neutron scattering and simultaneously recording their rheological properties. Two different gelation mechanisms are revealed. The triblock copolymer inherently forms elongated micelles, whose length increases by temperature to form worm-like micelles, thus promoting gelation. In contrast, Pluronic F127's micellization is temperature-driven, and its gelation is attributed to the close packing of the micelles. The gel structure is analyzed through cryogenic scanning and transmission electron microscopy. Ex vivo gelation study upon intracameral injections demonstrates excellent potential for its application to improve drug residence in the eye.
RESUMEN
Our group has recently invented a novel series of thermoresponsive ABC triblock terpolymers based on oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol-1 (OEGMA300, A unit), n-butyl methacrylate (BuMA, B unit) and di(ethylene glycol) methyl ether methacrylate (DEGMA, C unit) with excellent thermogelling properties. In this study, we investigate how the addition of OEGMA300x homopolymers of varying molar mass (MM) affects the gelation characteristics of the best performing ABC triblock terpolymer. Interestingly, the gelation is not disrupted by the addition of the homopolymers, with the gelation temperature (Tgel) remaining stable at around 30 °C, depending on the MM and content in OEGMA300x homopolymer. Moreover, stronger gels are formed when higher MM OEGMA300x homopolymers are added, presumably due to the homopolymer chains acting as bridges between the micelles formed by the triblock terpolymer, thus, favouring gelation. In summary, novel formulations based on mixtures of triblock copolymer and homopolymers are presented, which can provide a cost-effective alternative for use in biomedical applications, compared to the use of the triblock copolymer only.
RESUMEN
In this study, seven thermoresponsive methacrylate terpolymers with the same molar mass (MM) and composition but various architectures were successfully synthesized using group transfer polymerization (GTP). These terpolymers were based on tri(ethylene glycol) methyl ether methacrylate (TEGMA, A unit), n-butyl methacrylate (BuMA, B unit), and 2-(dimethylamino)ethyl methacrylate (DMAEMA, C unit). Along with the more common ABC, ACB, BAC, and statistical architectures, three diblock terpolymers were also synthesized and investigated for the first time, namely (AB)C, A(BC), and B(AC); where the units in the brackets are randomly copolymerized. Two BC diblock copolymers were also synthesized for comparison. Their hydrodynamic diameters and their effective pKas were determined by dynamic light scattering (DLS) and hydrogen ion titrations, respectively. The self-assembly behavior of the copolymers was also visualized by transmission electron microscopy (TEM). Both dilute and concentrated aqueous copolymer solutions were extensively studied by visual tests and their cloud points (CP) and gel points were determined. It is proven that the aqueous solution properties of the copolymers, with specific interest in their thermoresponsive properties, are influenced by the architecture, with the ABC and A(BC) ones to show clear sol-gel transition.
