Therapeutic Delivery Applications Research Articles

Synthesis of Customizable Macromolecular Conjugates as Building Blocks for Engineering Metal–Phenolic Network Capsules with Tailorable Properties

Metal–phenolic networks (MPNs), formed through coordination bonding between phenolic molecules and metal ions, are a promising class of materials for engineering particle systems for diverse applications. However, the properties of such MPNs are inherently restricted due to the finite properties of naturally occurring phenolic molecules. Herein, we report a simple and robust approach to incorporate phenolic moieties into polymers, thereby providing customizable phenolic ligand building blocks that can be used to assemble capsules with a range of tailorable properties. The phenolic ligand building blocks were synthesized via carbonic anhydride coupling to terminal amines, a conjugation approach typically used for peptide coupling but applied herein for functionalizing polymers. The chemistry enabled optimized end-group purity, thus affording a robust and efficient strategy to generate a library of macromolecular poly(ethylene glycol) (PEG) catechol building blocks with different architectures (i.e., 2-, 4-, and 8-arm) and molecular weights (from 2.5 to 20 kDa). The resulting phenolic building blocks were applied to fabricate capsules with shell thickness, permeability, and cell association properties that were controlled via the variation of the macromolecular catechol architecture and molecular weight. Specifically, the shell thickness was varied more than 19-fold (i.e., between ∼9 and 169 nm) by judicious selection of the polymer molecular weight, arm number, and template. Similarly, the permeability of the resulting MPN capsules to 500 kDa dextran was tuned from >90 to <5% by varying the number of arms in the polymer structure while maintaining a constant PEG Mn-to-catechol group ratio. Furthermore, the cell association was reduced by a factor of 2.5 by employing 20 kDa 8-arm PEG instead of 2.5 kDa 2-arm PEG during film assembly. These results demonstrate that the applied macromolecular conjugation approach can be used to customize particle properties, potentially facilitating applications in therapeutic delivery, imaging, separations, and catalysis.

Dissolving microneedle-assisted long-acting Liraglutide delivery to control type 2 diabetes and obesity

Integrating nanoparticles (NPs) as a smart and targeted tool for drug delivery with dissolving microneedle (DMN) patch, the non-invasive device for drug delivery, is a promising for future therapeutic delivery applications. Liraglutide (Lira) encapsulation in poly (lactic-co-glycolic acid) (PLGA) NPs provides a sustained release of Lira to 15 days in a biphasic profile which 80% of released content happens in the first 8 days. Embedding such sustained release NPs in the DMN comprising poly vinyl pyrrolidone (PVP) 50% w/v, eliminates the need for Lira subcutaneous injection. Additionally, NPs containing DMN enhance mechanical strength of needles to 5.31 N compared to DMN with pure Lira content which was 4.32 N. The flexible backing layer of the DMN was obtained via blending of PVP and poly vinyl alcohol (PVA) in 10% w/v. Circular dichroism (CD) analysis showed that Lira encapsulated in NPs maintained its native secondary structure even after solidification in DMN. In this study, the capacity of 2 kinds of 500 μm and 1000 μm needles to deliver the desired dose of drug was obtained based on experimental and mathematical methods.

Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting

Abstract Background: Accumulation of systemically administered nanoparticles (NPs) in lymph nodes has been exploited clinically for diagnostic imaging (e.g., USPIOs for lymph node metastasis) and therapeutic applications (e.g., vaccine delivery). However, the combination of diagnostic and therapeutic functionalities into a single theranostic NP has obliged undesirable trade-offs between either the imaging or drug delivery of the NP and their specific accumulation in lymph nodes. To overcome these trade-offs, we conducted a screen of various lipid-based theranostic NPs focusing on differing NP design and their resulting pharmacokinetic behaviours in healthy and diseased lymph node models. Methods: Lipid-based theranostic NPs with varying physicochemical characteristics (e.g., formulation, size and morphology, surface targeting, etc.) were prepared with positron emitting Cu-64 and administered systemically at equivalent NP doses in healthy and diseased rodent models (i.e., mice and rats). NP types were assessed for time-dependent accumulation in major lymph node basins via non-invasive whole-body PET/MR imaging at two or more timepoints per animal. 72-hours post-injection the animals were sacrificed, and lymph nodes and major organs were excised for gamma counting and pathological evaluation. Pharmacokinetic behaviour of NPs in healthy versus diseased lymph nodes were calculated in individual animals and in naïvely pooled datasets using non-compartmental analysis. Results: Preliminary analysis identified a leading NP candidate with specific lymph node targeting in healthy and diseased rodents: a discoidal, 35-nm peptide-targeted HDL-mimetic. In comparison with a spherical, 100-nm PEGylated NP, the discoidal NP obtained greater absolute (%ID) and relative (%ID/g) amounts of injected dose in anatomically matched lymph nodes than the spherical NP, regardless of lymph node pathology. At greatest measured concentration in healthy lymph nodes, typically 24-hpi, the differences between the discoidal and spherical NPs were on average 3-fold greater (2.893 vs. 0.864, %ID/g). Differences in other pharmacokinetic parameters such as AUC (%ID/g*h) and MRT (h) were equally pronounced. Conclusions: Our preliminary analysis uncovered a discoidal, peptide-targeted HDL-mimetic with remarkable accumulation in lymph nodes of healthy and diseased models. Future investigations will focus on the biochemical and cellular mechanisms underlying their unique lymphatic pharmacokinetics. These preliminary results provide key insights for design of theranostic NPs for non-invasive imaging and staging lymph node pathologies, and for applications in delivery of therapeutics to lymph nodes following systemic administration. Citation Format: Michael S. Valic, Mark Zheng, Lili Ding, Michelle Lai, Chris J. Zhang, Tina Ye, Jenny Ma, Michael Halim, Pamela Schimmer, Wenlei Jiang, Juan Chen, Gang Zheng. Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 307.

Microfluidic Based Physical Approaches towards Single-Cell Intracellular Delivery and Analysis.

The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great interest. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. This review article aims to cover various microfluidic-based physical methods for single-cell intracellular delivery such as electroporation, mechanoporation, microinjection, sonoporation, optoporation, magnetoporation, and thermoporation and their analysis. The mechanisms of various physical methods, their applications, limitations, and prospects are also elaborated.

Tailoring the growth and proliferation of human dermal fibroblasts by DNA-based polymer films for skin regeneration.

The use of DNA as a functional biomaterial for therapeutic, diagnostic, and drug delivery applications has been prominent in recent years, but its use as a scaffold for tissue regeneration is still limited. This study aimed to evaluate the biocompatibility and interaction of DNA-based polymeric films (DNA-PFs) with primary human fibroblasts (PHF) for regenerative medicine and wound healing purposes. The morphological characterization of the films was performed by scanning electron microscopy, SEM-energy-dispersive X-ray spectroscopy, and atomic force microscopy analysis. Cell viability, cell cycle kinetics, oxidative stress, and migration studies were carried out at 48 and 72 hr of incubation and compared to control cells. Cell adhesion was impaired in the first 24 hr, DNA-PFs with higher concentrations of DNA (1.0 and 2.0g/L) this effect was not seen in DNA-PFs (0.5g/L), explained by the difference in topography and roughness of DNA-PFs, but it was overcome after 48 hr of incubation. PHF seeded on DNA films showed higher proliferation and migration rates than the control after 48 hr of incubation, with the maintenance of cell morphology and lower cytotoxicity and oxidative stress during the evaluation time. Therefore, these results indicate that DNA-PFs are highly biocompatible and provide a suitable microenvironment for dermal fibroblasts to maintain their activity, helping build new and more complex biomaterials suitable for future tissue repair applications.

Oral cavity: An open horizon for nanopharmaceuticals

Oral administration is the primary route employed for drug delivery. In addition to the gastrointestinal tract, the oral cavity has been drawing considerable attention owing to its physiological properties and advances in drug carrier development. Notably, nanotechnology has made immense contributions to enhancing drug bioavailability, stability, and efficacy, both in research and clinical settings. The present review comprises lessons from physiological characteristics to fundamental material science knowledge, summarizing the pros and cons of nanotechnology applications in therapeutic drug delivery. The oral cavity presents inherent challenges, including oral cancer, dental caries, oral infection, or oral inflammation, that necessitate local solutions. Simultaneously, the vascular system under the tongue and in the buccal region offers a portal for systemic drug absorption. Among available delivery systems, nanoparticle-based drug delivery, with the oral cavity as the action or absorption site, can be developed as a principal dosage formulation. Although convenience and fast onset might be advantageous, additional studies are warranted for preclinical characterization, especially in animal models, and for determining manufacturing competence, prior to human trials to meet standards in clinical settings.

Polyphenol-Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery.

Polyphenols, the phenolic hydroxyl group-containing organic molecules, are widely found in natural plants and have shown beneficial effects on human health. Recently, polyphenol-containing nanoparticles have attracted extensive research attention due to their antioxidation property, anticancer activity, and universal adherent affinity, and thus have shown great promise in the preparation, stabilization, and modification of multifunctional nanoassemblies for bioimaging, therapeutic delivery, and other biomedical applications. Additionally, the metal-polyphenol networks, formed by the coordination interactions between polyphenols and metal ions, have been used to prepare an important class of polyphenol-containing nanoparticles for surface modification, bioimaging, drug delivery, and disease treatments. By focusing on the interactions between polyphenols and different materials (e.g., metal ions, inorganic materials, polymers, proteins, and nucleic acids), a comprehensive review on the synthesis and properties of the polyphenol-containing nanoparticles is provided. Moreover, the remarkable versatility of polyphenol-containing nanoparticles in different biomedical applications, including biodetection, multimodal bioimaging, protein and gene delivery, bone repair, antibiosis, and cancer theranostics is also demonstrated. Finally, the challenges faced by future research regarding the polyphenol-containing nanoparticles are discussed.

Therapeutic Properties of PDMS Nanoparticles: A Promising New Drug Delivery Vehicle against Inflammatory Conditions.

Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles help to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action. Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles. PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material are detailed herein. Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 μg/mL in culture. Biocompatibility and absence of toxicity were determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac. In this paper, we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.

Design, synthesis and biological applications of glycopolypeptides.

Carbohydrates play essential structural and biochemical roles in all living organisms. Glycopolymers are attractive as well-defined biomimetic analogs to study carbohydrate-dependent processes, and are widely applicable biocompatible materials in their own right. Glycopolypeptides have shown great promise in this area since they are closer structural mimics of natural glycoproteins than other synthetic glycopolymers and can serve as carriers for biologically active carbohydrates. This review highlights advances in the area of design and synthesis of such materials, and their biomedical applications in therapeutic delivery, tissue engineering, and beyond.

Modification of metal-organic framework composites as trackable carriers with fluorescent and magnetic properties

A fluorescent metal-organic framework (EuMOF) based on Eu3+ nodes coordinated by 1,1′:2′,1″-terphenyl-4,4′,4″,5′-tetracarboxylate (H4ttca) linkers has been developed as a trackable carrier with inherent fluorescence. Since Fe3O4 nanoparticles (NPs) have great value in versatile applications in vivo/vitro including imaging, cell isolation and magnetic responsivity, Fe3O4 NPs were introduced in the EuMOF composites to enhance the multifunctionalities. It has been demonstrated that the Fe3O4 NPs functionalized EuMOF composites have capability for tumor cell retrieval from matrix followed by anti-cancer drug release, which is promising to be developed as an integrated drug screening platform. Cytotoxicity was evaluated and the EuMOF-based nanocomposite exhibits significantly greater (up to 4x) biocompatibility tested on MCF-7 cells than the Zn-based MOF (the same ligand). Moreover, the EuMOF nanocarrier is capable of loading and releasing anti-cancer drugs in a controllable manner, where Doxorubicin (Dox) functionalized as a payload. Controllable release was successfully achieved after incubation with tumor cells and endocytosis analysis was obtained through the fluorescent imaging which offers monitoring of apoptosis after cargo release. Overall, fluorescent/magnetic properties of EuMOF has been investigated systematically, making it easy to be tracked in potential in vivo/vitro applications. As a drug carrier, it is biocompatible and shows highly efficient drug loading within 5 min, holding great promise in potential therapeutic delivery and other clinical applications.

Structural and Surface Properties of Polyamidoamine (PAMAM) – Fatty Acid‐based Nanoaggregates Derived from Self‐assembling Janus Dendrimers

AbstractThis study summarizes the synthesis, characterization, and evaluation of a library of biocompatible self‐assembling Janus dendrimers (JDs) and their resulting nanostructures possessing either a cationic (NH3+), anionic (COO−), or neutral (OH) surface. Strategically designed for applications in therapeutic delivery, the dendrimers are comprised of a polyamidoamine (PAMAM) dendron as the hydrophilic portion and fatty acid (FA) functionalized dendrons as the hydrophobic portion. The physicochemical characterization and in vitro cell viability of amphiphilic JDs were performed. Microscopy (TEM) and dynamic light scattering (DLS) analysis indicate the size (i. e., diameters) of spherical nanoaggregates ranging from 40 to 100 nm with zeta‐potential values ranging from −17.9 to +58.7 mV with respect to the terminal functional group of the JD employed. Furthermore, these systems exhibited spherical nanoaggregates with critical aggregate concentrations (CAC) ranging from 2.8 to 7.0 mg/L. At low concentrations (&lt;200 μg/mL), JDs nanoaggregates showed minimal cell growth inhibitory properties in the in vitro testing, demonstrating their safety. The results of this study prove that a simple yet strategic combination of chemically distinctive dendritic segments can afford a versatile library of unique JDs nanoplatforms with excellent potential for biomedical applications.

Recent developments in stimuli-responsive polymer nanogels for drug delivery and diagnostics: A review

Polymer nanogels (NGs) are water-swellable, cross-linked 3D network structures with size typically range from 1 to 1000 nm. Especially, biocompatible and “smart” NGs engineered from stimuli-responsive polymers are attractive because of its capability to respond the endogenous biological triggers of pH, bioreduction, biomolecule recognition, as well as the exogenous stimuli-triggers like temperature and light. Importantly, on exposing to these physical or biochemical signals, the responsive NGs can be utilized for therapeutic delivery and diagonostic applications. In the past decade, substantial developments were achieved in the development of “smart” NGs for theranostic and diagnostic applications such as intracellular delivery of drug and nucleic acids, photodynamic/photothermal therapy, bioimaging and sensing. Herein, we exclusively review the recent exciting developments in synthetic methods as well as biomedical applications of successfully employed “smart” NGs which can respond to a single, dual or multiple stimulus- responsive triggers. The prospects in the application of the stimuli-responsive and multifunctional NGs also will be addressed in this review.

Oral GLP1 Gene Delivery by an Antibody-Guided Nanomaterial to Treat Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic and progressive hyperglycemic condition. Glucagon-like peptide-1 (GLP1) is an incretin secreted from pancreatic β-cells and helps to produce insulin to balance the blood glucose level without the risk of hypoglycemia. However, the therapeutic application of GLP1 is limited by its intrinsic short half-life and rapid metabolic clearance in the body. To enhance the antidiabetic effect of GLP1, we designed a human cysteine-modified IgG1-Fc antibody-mediated oral gene delivery vehicle, which helps to produce GLP1 sustainably in the target site with the help of increased half-life of the Fc-conjugated nanocarrier, protects GLP1 from acidic and enzymatic degradation in the gastrointestinal (GI) tract, uptakes and transports the GLP1 formulation through the neonatal Fc receptor (FcRn), and helps to release the GLP1 gene in the intestine. Our formulation could reduce the blood glucose from about an average of 320 mg/dL (hyperglycemic) to 150 mg/dL (normal blood glucose concentration) in diabetic mice, which is about 50% reduction of the total blood glucose concentration. GLP1 (500 μg) complexed with the IgG1-Fc carrier was proven to be the optimal dose for a complete reduction of hyperglycemic conditions in diabetic mice. A significant amount of insulin production and the presence of GLP1 peptide were observed in the pancreatic islets of oral GLP1 formulation-treated diabetic mice in immunohistochemistry analysis compared to nontreated diabetic mice. The orally given formulation was completely nontoxic according to the histopathology analysis of mice organ tissues, and no mice death was observed. Our antibody-mediated oral gene delivery system is a promising tool for various oral therapeutic gene delivery applications to treat diseases like diabetes.

Lightweight Learning-Based Automatic Segmentation of Subretinal Blebs on Microscope-Integrated Optical Coherence Tomography Images

Subretinal injections of therapeutics are commonly used to treat ocular diseases. Accurate dosing of therapeutics at target locations is crucial but difficult to achieve using subretinal injections due to leakage, and there is no method available to measure the volume of therapeutics successfully administered to the subretinal location during surgery. Here, we introduce the first automatic method for quantifying the volume of subretinal blebs, using porcine eyes injected with Ringer's lactate solution as samples. Ex vivo animal study. Microscope-integrated optical coherence tomography was used to obtain 3D visualization of subretinal blebs in porcine eyes at Duke Eye Center. Two different injection phases were imaged and analyzed in 15 eyes (30 volumes), selected from a total of 37 eyes. The inclusion/exclusion criteria were set independently from the algorithm-development and testing team. A novel lightweight, deep learning-based algorithm was designed to segment subretinal bleb boundaries. A cross-validation method was used to avoid selection bias. An ensemble-classifier strategy was applied to generate final results for the test dataset. The algorithm performs notably better than 4 other state-of-the-art deep learning-based segmentation methods, achieving an F1 score of 93.86 ± 1.17% and 96.90 ± 0.59% on the independent test data for entry and full blebs, respectively. The proposed algorithm accurately segmented the volumetric boundaries of Ringer's lactate solution delivered into the subretinal space of porcine eyes with robust performance and real-time speed. This is the first step for future applications in computer-guided delivery of therapeutics into the subretinal space in human subjects.

Ionic Liquids for Therapeutic and Drug Delivery Applications.

Ionic liquids (ILs) are ionic compounds with highly tunable and remarkable properties which make them an important candidate in multiple domains such as extraction, synthesis, analytics, catalysis, biotechnology, therapeutics as well as pharmaceutical sciences. This review systematically highlights the classification, properties and toxicity of ionic liquids. It focuses on exploring the biological activity of ionic liquids, which includes antimicrobial and anticancer property along with an emphasis on the concept of Active Pharmaceutical Ingredient- Ionic Liquids (API-ILs) for explaining the emulsifier and solubility enhancement property of ILs. An elaborative discussion on the application of ILs for the development of oral, transdermal and topical drug delivery systems has also been presented with suitable literature support. Ionic liquids possess exceptional potential in the field of medicine, biology and chemistry.

Quantum Dots in Therapeutic, Diagnostic and Drug Delivery Applications “A Brief Review”

Quantum Dots in Therapeutic, Diagnostic and Drug Delivery Applications “A Brief Review”

Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications.

Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with certain drugs (due to hydrophilicity or charge repulsion interactions) limits its use. Combining PLGA or other polymers such as polycaprolactone with other safe and positively-charged molecules, such as chitosan, has been sought after to make hybrid systems that are more flexible in terms of loading ability, but often the reactions for polymer coupling use harsh conditions, films, unpurified products, or create a single unoptimized product. In this work, we aimed to investigate possible innovative improvements regarding two synthetic procedures. Two methods were attempted and analytically compared using nuclear magnetic resonance (NMR), fourier-transform infrared spectroscopy (FT-IR), and dynamic scanning calorimetry (DSC) to furnish pure, homogenous, and tunable PLGA-chitosan hybrid polymers. These were fully characterized by analytical methods. A series of hybrids was produced that could be used to increase the suitability of PLGA with previously non-compatible drug molecules.

Exploiting Cell‐Instructive Nanocomposites for Tissue Engineering, Bio‐printing and Therapeutics Applications

Considerable effort has recently been directed towards the development of hydrogels for tissue engineering and printing complex tissues in 3D, as they can mimic the physical, chemical, and biological properties of most biological tissues. Dr. Paul, in his talk, will highlight the immense potential various bioactive nanomaterials (e.g. mineral based nanoparticles), biopolymers (e.g. DNA, gelatin) and their nanocomposites to develop advanced multifunctional hydrogels for additive manufacturing and therapeutic delivery applications, as well as to effectively control stem cell fate in a 3D microenvironment.Support or Funding InformationAP acknowledges the funding and support from Canada Research Chairs Program of the Natural Sciences and Engineering Research Council (NSERC) of Canada.

Molecular imaging of extracellular vesicles in vitro via Raman metabolic labelling.

Extracellular vesicles (EVs) are biologically-derived nanovectors important for intercellular communication and trafficking. As such, EVs show great promise as disease biomarkers and therapeutic drug delivery vehicles. However, despite the rapidly growing interest in EVs, understanding of the biological mechanisms that govern their biogenesis, secretion, and uptake remains poor. Advances in this field have been hampered by both the complex biological origins of EVs, which make them difficult to isolate and identify, and a lack of suitable imaging techniques to properly study their diverse biological roles. Here, we present a new strategy for simultaneous quantitative in vitro imaging and molecular characterisation of EVs in 2D and 3D based on Raman spectroscopy and metabolic labelling. Deuterium, in the form of deuterium oxide (D2O), deuterated choline chloride (d-Chol), or deuterated D-glucose (d-Gluc), is metabolically incorporated into EVs through the growth of parent cells on medium containing one of these compounds. Isolated EVs are thus labelled with deuterium, which acts as a bio-orthogonal Raman-active tag for direct Raman identification of EVs when introduced to unlabelled cell cultures. Metabolic deuterium incorporation demonstrates no apparent adverse effects on EV secretion, marker expression, morphology, or global composition, indicating its capacity for minimally obstructive EV labelling. As such, our metabolic labelling strategy could provide integral insights into EV biocomposition and trafficking. This approach has the potential to enable a deeper understanding of many of the biological mechanisms underpinning EVs, with profound implications for the design of EVs as therapeutic delivery vectors and applications as disease biomarkers.

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

ABSTRACTpH responsive hydrogels are ideal platforms for numerous therapeutic delivery applications, including oral delivery, as they are capable of overcoming the many barriers that must be considered when creating an effective drug delivery system. Understanding of the innate hydrogel network structure and its swelling behavior at environmentally relevant conditions is vital for designing hydrogel network capable of effective controlled drug release. Herein, we explored how to expand traditional techniques of swelling and pore characterization to gain better insight into the performance of anionic microparticles composed of the poly(methyl methacrylate‐co‐acrylic acid) with varying molar percentage of 10, 20, and 30 mol% of MMA, for controlled release of low‐molecular‐weight drugs. By evaluating these carrier systems at environmental conditions, we can observe changes in swelling and pore size of the anionic hydrogel networks as a function of MMA, which was then correlated with the release profiles of the small‐molecular‐weight drug sodium nitrate. With the correlation of the swelling behavior of the networks and the release profiles, we demonstrated how the expansion of swelling parameters at relevant pH values provides further incite for evaluating for the optimal blend for controlled release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48767.