External vs. internal crosslinking: Impact on praziquantel release from chitosan microparticles for oral delivery

Itaconic acid (IA) is a bio-based unsaturated monomer, which has been limitedly used in free-radical polymerization due to low reactivity of its carbon-carbon double bond and lack of tendency toward homo-polymerization. In the present work, IA was modified with glyceryl methacrylate (GMA) or epichlorohydrin (ECH) to synthesize two new IA-based materials, i.e., IA-GMA and IA-ECH, respectively. After the characterization of the crosslinkers by 1H NMR and FTIR, IA-GMA containing two methacrylate groups in the structure was used as an internal crosslinker for the preparation of a superabsorbent polymer (SAP). The obtained IA-GMA crosslinked SAP showed a high water absorbency under load (AUL) up to 23.9 g/g compared to commercial SAPs (14–18 g/g), so it can be a potential crosslinker for SAP preparation without a requirement of the surface treatment process as a time and energy-consuming process. Moreover, the application of IA-ECH, possessing hydroxyl or epoxy functionalities as an internal and surface crosslinker in the synthesis of SAPs was investigated. The unique ion structure of IA-ECH as an external crosslinker resulted in improvement in gel strength, as well as AUL up to 30.7 g/g. The SAPs crosslinked by IA-ECH as internal crosslinker presented a high water absorbency (Qw) and saline absorbency (Qs).

Tailoring swelling of alginate-gelatin hydrogel microspheres by crosslinking with calcium chloride combined with transglutaminase

Latexes have many product applications including functioning as a binder in coatings. For many years, coatings researchers in industry as well as in academe have been exploring various modes of crosslinking latexes. Quite often, the goal of preparing crosslinked latexes is to upgrade film properties relative to the film properties of uncrosslinked latexes. In the present report, the synthesis and properties of crosslinkable acrylic latexes prepared with either an internal crosslinker (1,3-butylene glycol dimethacrylate)—“precoalescence crosslinking”—or an external crosslinker (adipic dihydrazide)—“postcoalescence crosslinking”—at various levels of crosslinking were studied. For postcoalescence crosslinking, diacetone acrylamide was copolymerized into the latex to provide sites for subsequent reaction with adipic dihydrazide. Fundamental properties of films cast from the two types of latexes were systematically compared. These properties included gel content, dynamic mechanical properties, nano-indenter hardness and modulus, stress–strain properties as well as the characterization of latex morphology by atomic force microscopy (AFM). In addition, some specific end-use properties were determined. This study assesses the effect of type (precoalescence or postcoalescence) and level of crosslinking on the film formation process and the resulting fundamental and end-use properties as well as resulting latex film morphology.

Transport of biological molecules in surfactant–alginate composite hydrogels

Multifunctional films based on tannic acid-coated cellulose nanocrystals and zinc-coating reinforced sodium carboxymethyl cellulose/polyvinyl alcohol for food active packaging.

Hydrogels are three-dimensional and stable networks that possess the ability to absorb substantial amounts of water or biological fluids. Injectable hydrogels show great potential as versatile drug delivery platforms in regenerative and restorative medicine by offering non-invasive conditions and reducing time and cost. Xanthan gum (XG) and carboxymethyl cellulose (CMC), which are biocompatible, biodegradable and have high hydrophilic properties, are biopolymers whose value is increasing in the biomedical field. In this study, we present a dual ionic crosslinking method to form physiologically stable XG and CMC hydrogels using two distinct sources of calcium ions (Ca²⁺). This study aims to develop, analyze, and compare XG and CMC hydrogels synthesized using internal and external ionic crosslinking techniques. Our findings confirmed the successful synthesis of XG and CMC hydrogels through double crosslinking, utilizing internal gelation with CaSO₄·2H₂O and external ionic gelation with CaCl₂. As polymer concentrations increased, hydrogel stiffness also increased, while swelling and degradation rates decreased. Injectable XG and CMC hydrogels exhibited similar trends in rheological behavior, swelling, and degradation profiles. However, when XG and CMC hydrogels at the same concentration were compared, XG hydrogels exhibited slightly higher mechanical properties than CMC hydrogels. In summary, injectable xanthan gum and carboxymethyl cellulose hydrogels, obtained through double ionic crosslinking, can be utilized as drug delivery-release systems for applications in regenerative and reconstructive medicine.

The diverse structures and unique properties of hydrogels have attracted significant attentions in recent years. Compared to chemically cross-linked hydrogels, natural polymer-based hydrogels cross-linked with physical interactions are environmentally friendly owning to the free of chemical cross-linking agents and exhibit many advantages as diverse reversible non-covalent bonds. This review aims to summarize instructive strategies for designing physical hydrogels based on non-covalent bonds derived from unique functional groups of natural polymers to develop various unique properties and extend the application of corresponding hydrogels. Firstly, strategies to construct the natural polymer-based physically crosslinked hydrogels (NPPCHs) with internal and external stimulating cross-linking characteristics will be introduced. Internal effects included hydrogen bonding, ionic cross-linking, electrostatic interaction, hydrophobic association, and host-guest interaction, and external causes can be temperature, light, pH, or other conditions. Secondly, the unique advantages of processing technologies of NPPCHs including injection, 3D printing, spraying, and molding will be summarized. Thirdly, excellent performances of NPPCHs derived from unique dynamic non-covalent bond structures, such as self-healing, conductivity-promoting, and stimulus-response will be introduced. This review provides guidance to develop the NPPCHs with fascinating structures, excellent properties, and outstanding performances, which will play an important role in promoting the development of physically cross-linked hydrogels.

Hypercrosslinked polymers (HCPs) are widely used in ion exchange, water purification, and gas separation. However, HCP synthesis typically requires hazardous halogenated solvents e. g., dichloroethane, dichloromethane and chloroform which are toxic to human health and environment. Herein we hypothesize that the use of halogenated solvents in HCP synthesis can be overcome with deep eutectic solvents (DES) comprising metal halides-FeCl3 , ZnCl2 that can act as both the solvent hydrogen bond donor and catalyst for polymer crosslinking via Friedel Crafts alkylation. We validated our hypothesis by synthesizing HCPs in DESs via internal and external crosslinking strategies. [ChCl][ZnCl2 ]2 and [ChCl][FeCl3 ]2 was more suitable for internal and external hypercrosslinking, respectively. The specific surface areas of HCPs synthesized in DES were 20-60 % lower than those from halogenated solvents, but their CO2 /N2 selectivities were up to 453 % higher (CO2 /N2 selectivity of poly-α,α'-dichloro-p-xylene synthesized in [ChCl][ZnCl2 ]2 via internal crosslinking reached a value of 105). This was attributed to the narrower pore size distributions of HCPs synthesized in DESs.

Application of a self-crosslinking strategy based on oxidization modification for the preparation of soy-based adhesive

In this paper, isophorone diisocyanate (IPDI), polyethylene glycol (PEG), dimethylolpropionic acid (DMPA) and internal crosslinking agent trimethylolpropane (TMP) were used to prepare waterborne polyurethane. And then double-crosslinked polyurethane-acrylic composite aqueous dispersion was prepared in which polyacrylate was adopted to modify waterborne polyurethane and some special external crosslinking agents were added including silicone and trifunctional aziridine. The influence of the amounts of internal and external crosslinking agents, emulsifier, initiator on the particle size, particle size distribution, viscosity, molecular weight, as well as water adsorption ratio were studied.

Chitosan microparticles with modified surface chemistries as drug carriers: A study on their interactions in a simulated intestinal microenvironment.

Uptake of particulate antigen carrier systems by specialized M-cells of the gut-associated lymphoid tissue is still a limiting step in inducing efficient immune responses after oral vaccination. Although transport of soluble drugs over the epithelial barrier of the gut is extensively studied in vitro by using the Caco-2 cell model, this was for long time not possible for particles due to the absence of M-cells. By co-culturing Caco-2 cells with cultured human B-lymphocytes (Raji-cells), cells which are morphologically and functionally similar to M-cells can be induced. This human M-cells model makes it possible to study the uptake of microparticles for oral vaccine delivery. In this way, chitosan microparticles, which have demonstrated to target the Peyer's patches efficiently in vivo, could be tested in vitro. The development of this M-cells model facilitates the optimization of the microparticles in order to target them even more efficiently to the M-cells in the gut. In this study, the integrity of the human M-cell model was investigated by determining the transepithelial electrical resistance (TEER), 14 C-mannitol transport and morphology using scanning electron microscopy. The uptake of particles was investigated by measuring transport of both fluorescently labeled microspheres (Fluospheres ®) and chitosan microparticles using flowcytometry. No discontinuities or abnormalities could be found in the co-culture. Scanning electron microscopy showed that morphologically different cells were present in the human M-cell model. Both commercially available Fluospheres ® (size 0.2 μ m) and chitosan microparticles (size 1.7 μ m) for oral vaccine delivery were transported at a significantly higher amount by the human M-cell model compared to the transport by the Caco-2 cell monoculture. Since chitosan microparticles were proven to be taken up by Peyer's patches in mice as well, this human M-cell model is able to predict the M-cell uptake of microparticles for oral vaccine delivery. This M-cell model is a new tool, which can be used to scan, develop and optimize microparticles for oral vaccine delivery. Since the M-cell uptake can now be studied in vitro, the targeting of these cells can be studied more efficiently and can now be done in cells from human origin.

Chitosan microparticles containing plasmid DNA as potential oral gene delivery system

Systemic and local immune response against Chitosan encapsulated tetanus toxoid (CS-TT) microparticles is studied, prepared by ionic cross-linking using Sodium Tripolyphosphate (STPP). Final formulation was evaluated in terms of release of TT in 0.1 N HCl and PBS (pH 7.4), sedimentation profile and stability. CS-TT microparticles, TT in PBS and plain CS microparticles were orally administered to mice and TT (adsorbed) was administered through intramuscular route. Sera were analyzed for anti-TT IgG and intestinal lavage, faeces, intestinal washings for anti-TT IgA levels using an ELISA. Entrapment efficiency of about 100% was obtained. A dose dependent immune response was observed in mice vaccinated with Chitosan-TT microparticles. A strong enhancement of the systemic and local immune response against TT were found when compared with oral feeding of TT in PBS. The study shows the efficacy of chitosan microparticle suspension system, containing a high molecular protein (TT), in inducing the IgA in intestine and IgG in systemic circulation. This demonstrates that chitosan microparticles can prove to be a promising oral vaccine delivery system for mucosal and systemic immunity.

Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (Purpose: Toformulate glutaraldehyde-cross-linked chitosan-based microparticles and evaluate its suitability for the delivery of ibuprofen, a BCS class II drug. Methods : Ibuprofen-loaded chitosan microparticles were prepared by emulsification-cross-linking technique using glutaraldehyde saturated toluene (GST) as the cross-linking agent. The microparticles were characterized with respect to morphology, particle size, microparticle yield and entrapment efficiency. The swelling behaviour of the particles and ibuprofen release were assessed in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). Results : Discrete and free-flowing microparticles of size range 100.05 ± 8.82 to 326.70 ± 10.43 im were obtained. The microparticles had a high yield (69.2 to 99.2 %) and exhibited greater water sorption capacity in SIF (122.2 %) than in SGF (60 %). Furthermore, the microparticles cross-linked with 10 ml of GST entrapped the highest amount of drug (23.32 ± 0.97 %) while those cross-linked with 25 ml GST had the highest yield of the microparticles (99.19 % ), and highest water sorption in SIF (122.2 %). Up to 93.6 % of the entrapped drug was released in SIF from microparticles cross-linked with 25 ml of GST. Drug release from microparticles cross-linked with 20 and 30 ml each of GST showed a biphasic pattern. Conclusions : Entrapment of ibuprofen in glutaraldehyde-cross-linked chitosan microparticles can be exploited to target and control the release of the drug and possibly reduce its gastro-erosive side effects. Keywords : Chitosan microparticles, Ibuprofen, Oral delivery, Gastrointestinal, Glutaraldehyde.