Downregulation of C1R promotes hepatocellular carcinoma development by activating HIF-1α-regulated glycolysis.

C1R has been identified to have a distinct function in cutaneous squamous cell carcinoma that goes beyond its role in the complement system. However, it is currently unknown whether C1R is involved in the progression of hepatocellular carcinoma (HCC). HCC tissues were used to examine C1R expression in relation to clinical and pathological factors. Malignant characteristics of HCC cells were assessed through in vitro and in vivo experiments. The mechanism underlying the role of C1R in HCC was explored through RNA-seq, methylation-specific PCR, immuno-precipitation, and dual-luciferase reporter assays. This study found that the expression of C1R decreased as the malignancy of HCC increased and was associated with poor prognosis. C1R promoter was highly methylated through DNMT1 and DNMT3a, resulting in a decrease in C1R expression. Downregulation of C1R expression resulted in heightened malignant characteristics of HCC cells through the activation of HIF-1α-mediated glycolysis. Additionally, decreased C1R expression was found to promote xenograft tumor formation. We found that C-reactive protein (CRP) binds to C1R, and the free CRP activates the NF-κB signaling pathway, which in turn boosts the expression of HIF-1α. This increase in HIF-1α leads to higher glycolysis levels, ultimately promoting aggressive behavior in HCC. Methylation of the C1R promoter region results in the downregulation of C1R expression in HCC. C1R inhibits aggressive behavior in HCC in vitro and in vivo by inhibiting HIF-1α-regulated glycolysis. These findings indicate that C1R acts as a tumor suppressor gene during HCC progression, opening up new possibilities for innovative therapeutic approaches.

Protocol for in vivo nucleic acid delivery utilizing the rolling microneedle electrode array.

Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids. For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1.

Highly swellable, cytocompatible and biodegradeable guar gum-based hydrogel system for controlled release of bioactive components of liquorice (Glycyrrhiza glabra L.): Synthesis and evaluation.

Glycyrrhiza glabra Linn (liquorice) has been widely used for therapeutic purposes to treat digestive disorders, immunomodulatory disorders, inflammatory disorders, diabetes, viral infections, and cancer. Liquorice contains a wide variety of bioactive compounds, including glycyrrhizin, flavonoids, and terpenoids. Several factors compromise their therapeutic efficacy, such as poor pharmacokinetic profiles and physicochemical properties. Therefore, to improve its overall effectiveness, liquorice solid dispersion (LSD) was incorporated into biopolymer-based guar gum-grafted-2-acrylamido-2-methylpropane sulfonic acid (Guar gum-g-AMPS) hydrogels designed for controlled delivery via the oral route and characterized. The qualitative analysis of LSD revealed 51 compounds. Hydrogel structural properties were assessed for their effect on swelling and release. The highest swelling ratio (6413 %) and drug release (84.12 %) occurred at pH 1.2 compared to pH 7.4 (swelling ratio of 2721 % and drug release of 79.36 %) in 48 h. The hydrogels exhibited high porosity (84.23 %) and biodegradation (9.30 % in 7 days). In vitro hemolysis tests have demonstrated the compatibility of the hydrogel with blood. CCK-8 assay confirmed the biocompatibility of the synthesized hydrogel using osteoblasts and RIN-m5f cells. LSD exhibited good anti-inflammatory activity when loaded into hydrogels after being subjected to protein denaturation experiments. Moreover, LSD-loaded hydrogels have good antioxidant and antibacterial properties.

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo.

Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the in vivo nucleic acids delivery faces significant biological challenges. Lipid nanoparticles (LNPs) possess several advantages, such as simple preparation, high stability, efficient cellular uptake, endosome escape capabilities, etc., making them suitable for delivery vectors. However, the extensive hepatic accumulation of LNPs poses a challenge for successful development of LNPs-based nucleic acid therapeutics for extrahepatic diseases. To overcome this hurdle, researchers have been focusing on modifying the surface properties of LNPs to achieve precise delivery. The review aims to provide current insights into strategies for LNPs-based organ-selective nucleic acid delivery. In addition, it delves into the general design principles, targeting mechanisms, and clinical development of organ-selective LNPs. In conclusion, this review provides a comprehensive overview to provide guidance and valuable insights for further research and development of organ-selective nucleic acid delivery systems.

Neutrophil Extracellular Traps in Tumors and Potential Use of Traditional Herbal Medicine Formulations for Its Regulation.

Neutrophil extracellular traps (NETs) are extracellular fibers composed of deoxyribonucleic acid (DNA) and decorated proteins produced by neutrophils. Recently, NETs have been associated with the development of many diseases, including tumors. Herein, we reviewed the correlation between NETs and tumors. In addition, we detailed active compounds from traditional herbal medicine formulations that inhibit NETs, related nanodrug delivery systems, and antibodies that serve as "guiding moieties" to ensure targeted delivery to NETs. Furthermore, we discussed the strategies used by pathogenic microorganisms to evade NETs.

The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

Study on the ameliorative effect of honeysuckle on DSS-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Honeysuckle, first documented in the Miscellaneous Records of Famous Physicians, is known for its ability to expel toxin and cool blood to stop diarrhea. Modern pharmacological research has shown that honeysuckle has anti-inflammatory, antibacterial, antioxidant, and immune-regulating effects and is widely used in clinical practice. However, the effect of honeysuckle on ulcerative colitis (UC) is still not fully understood, which presents challenges for quality control, research and development. AIM OF THE STUDY: This study aimed to determine the anti-inflammatory properties and mechanism of action of aqueous extracts of honeysuckle in the treatment of ulcerative colitis. MATERIALS AND METHODS: The dextran sodium sulfate (DSS) induced-ulcerative colitis mouse model was established, and the mice were divided into five groups: the control group, the model group, and the low, medium, and high dose honeysuckle treatment groups. RESULTS: All dose groups of honeysuckle were found to significantly reduce IL-6 and TNF-α levels and regulate DSS-induced mRNA levels of CLDN4, COX-2, IL-6, INOS, MUC-2, occludin and NLRP3. The high-dose group displayed the most effective inhibition, and a differentially expressed mRNA detection indicated abnormal mRNA expression. The 16sRNA sequencing revealed that the honeysuckle was able to significantly upregulate the abundance of beneficial bacteria and downregulate the abundance of harmful bacteria. The study of short-chain fatty acids revealed that the levels of acetic, propionic, isobutyric, valeric and isovaleric acids were significantly increased after administering honeysuckle at medium and high doses. CONCLUSION: Honeysuckle reduces the production of pro-inflammatory cytokines, increases the content of short-chain fatty acids and restores the intestinal ecological balance, resulting in better therapeutic effects.

Visualization of nasal powder distribution using biomimetic human nasal cavity model.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Extraction of cellulose nanocrystalline from Camellia oleifera Abel waste shell: Study of critical processes, properties and enhanced emulsion performance.

Cellulose nanocrystals (CNCs) extracted from the waste shell of Camellia oleifera Abel (C. oleifera) are gaining attention as valuable materials. In this study, CNCs were extracted from the agricultural waste shell of C. oleifera through phosphoric acid and sulfuric acid hydrolysis, respectively. Firstly, we optimized the alkaline treatment process for cellulose isolation by using response surface methodology. Furthermore, the properties of CNCs were investigated by neutralizing them with NaOH and NH3·H2O, and by dialysis in water. In addition, the characterization methods including FT-IR, TGA, AFM and TEM were used to analysis the properties of the synthesized CNCs. Finally, CNCs were studied for their application in essential oil-based Pickering emulsions. CNCs obtained from sulfuric acid showed the smallest particle size and good dispersibility. Moreover, the release profiles of essential oils in the emulsions were followed by Peppa's kinetic release model. The antibacterial activity of the emulsions against E. coli and S. aureus showed that CNCs-stabilized emulsions enhanced the antibacterial activity of essential oils. Therefore, neutralization treatments may enhance the properties of CNCs, and CNCs stabilized Pickering emulsions can enhance antibacterial activity of essential oil. This study provides insight into the potential application of CNCs derived from C. oleifera waste shells.

Hydroxyethyl Cellulose-Based Hydrogels as Controlled Release Carriers for Amorphous Solid Dispersion of Bioactive Components of Radix Paeonia Alba.

Radix Paeoniae Alba (RPA) has been used extensively in Chinese traditional medicine to treat gastrointestinal disorders, immune-modulating diseases, cancers, and numerous other conditions. A few of its active components include paeoniflorin, albiflorin, lactiflorin, and catechin. However, their therapeutic effectiveness is compromised by poor pharmacokinetic profiles, low oral bioavailability, short half-lives, and poor aqueous solubility. In this study, hydroxyethyl cellulose-grafted-2-acrylamido-2-methylpropane sulfonic acid (HEC-g-AMPS) hydrogels were successfully prepared for the controlled release of Radix Paeonia Alba-solid dispersion (RPA-SD). A total of 43 compounds were identified in RPA-SD using UHPLC-Q-TOF-MS analysis. The hydrogel network formation was confirmed by FTIR, TGA, DSC, XRD, and SEM. Hydrogels' swelling and drug release were slightly higher at pH 1.2 (43.31% swelling, 81.70% drug release) than at pH 7.4 (27.73% swelling, 72.46% drug release) after 48 h. The gel fraction, drug release time and mechanical strength of the hydrogels increased with increased polymer and monomer concentration. Furthermore, the hydrogels were porous (84.15% porosity) and biodegradable (8.9% weight loss per week). Moreover, the synthesized hydrogels exhibited excellent antimicrobial and antioxidative properties.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

Interactions of Essential Oil Components to Their Payloads in Supramolecular Particulate Carriers of Cyclodextrin Metal-Organic Frameworks.

Essential oil (EO) is widely used in the pharmaceutical, cosmetic, agriculture, and food industries because of its aromatic, antioxidant, and antibacterial properties. However, the weak interactions caused by small contact area with various substrates pose significant challenges to experimental detection and molecular simulation. In this study, the main components and contents of compound essential oil (CEO) were determined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography (GC), respectively. As a result, 11 components were screened out from CEO and their contents were measured. And synthetic essential oil (SEO) was deployed as a simplified CEO model for subsequent research according to the above result. In addition, a porous cyclodextrin metal-organic framework (CD-MOF) was used to load SEO, and the detailed process of experimental determination and molecular simulation prediction of the content of volatile oil components in CD-MOF was shown. The results of experiments and molecular simulations have consistently proved that CD-MOF had a selective absorption effect on SEO components. Furthermore, the interaction mechanism and release characteristics of these components in CD-MOF were investigated. The results of the release kinetics analysis provided references for the identification of the diffusion type of each component. In conclusion, the strategies established in this article provide ideas for the experimental detection and molecular simulation of multi-component competitive existence in carriers under weak interactions.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design.

Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.

Cross-scale tracing of nanoparticles and tumors at the single-cell level using the whole-lung atlas.

Currently, the effectiveness of oncotherapy is limited by tumor heterogeneities, which presents a huge challenge for the development of nanotargeted drug delivery systems (DDSs). Therefore, it is important to resolve the spatiotemporal interactions between tumors and nanoparticles. However, targeting evaluation has been limited by particle visualization due to the gap between whole-organ scale and subcellular precision. Here, a high-precision three-dimensional (3D) visualization of tumor structure based on the micro-optical sectioning tomography (MOST) system and fluorescence MOST (fMOST) system is presented to clarify 3D spatial distribution of nanoparticles within the tumor. We demonstrate that through the MOST/fMOST system, it is possible to reveal multidimensional and cross-scale correlations between the tumor structure and nanoparticle distribution to remodel the tumor microenvironment and explore the structural parameters of vasculature. This visualization methodology provides an accurate assessment of the efficacy, distribution, and targeting efficiency of DDSs for oncotherapy compared to available approaches.

Correlations between flavor and fermentation days and changes in quality-related physiochemical characteristics of fermented Aurantii Fructus.

The effects of different fermentation times (0, 1, 2, 3, 4, and 5 days) on the physicochemical properties and flavor components of fermented Aurantii Fructus (FAF) were evaluated. Component analysis identified 66 compounds in positive ion mode and 32 compounds in negative ion mode. Flash GC e-nose results showed that propanal, (+)-limonene and n-nonanal may be the flavor characteristic components that distinguish FAF with different fermentation days. Furthermore, we found that the change of total flavonoid content was closely related to colony growth vitality. The total flavonoid content of FAF gradually decreased from 3rd day and then increased from 5th day (3rd day: 0.766 ± 0.123 mg/100 g; 4th day: 0.464 ± 0.001 mg/100 g; 5th day: 0.850 ± 0.192 mg/100 g). Finally, according to antioxidant activity correlation analysis, meranzin, (+)-limonene and total flavonoids were found to be the key substances affecting the fermentation days of FAF. Overall, the optimal fermentation time for FAF was 4 days.

Solvent-Free Loading of Vitamin A Palmitate into ß-Cyclodextrin Metal-Organic Frameworks for Stability Enhancement.

Cyclodextrin metal-organic frameworks (CD-MOFs) exhibit a high structural diversity, which contributes to their functional properties. In this study, we have successfully synthesized a novel type of ß-cyclodextrin metal-organic framework (ß-CD-POF(I)) that exhibits excellent drug adsorption capacity and enhances stability. Single-crystal X-ray diffraction analysis revealed that ß-CD-POF(I) possessed the dicyclodextrin channel moieties and long-parallel tubular cavities. Compared with the reported ß-CD-MOFs, the ß-CD-POF(I) has a more promising drug encapsulation capability. Here, the stability of vitamin A palmitate (VAP) was effectively improved by the solvent-free method. Molecular modeling and other characterization techniques like synchrotron radiation Fourier transform infrared spectroscopy (SR-FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen adsorption isotherm were applied to confirm that the VAP was successfully encapsulated into the channel formed by the dicyclodextrin pairs. Furthermore, the mechanism of stability enhancement for VAP was determined to be due to the constraint and separation effects of ß-CD pairs on VAP. Therefore, ß-CD-POF(I) is capable of trapping and stabilizing certain unstable drug molecules, offering benefits and application possibilities. One kind of cyclodextrin particle with characteristic shapes of dicyclodextrin channel moieties and parallel tubular cavities, which was synthesized by a facile process. Subsequently, the spatial structure and characteristics of the ß-CD-POF(I) were primarily confirmed. The structure of ß-CD-POF(I) was then compared to that of KOH-ß-CD-MOF, and a better material for vitamin A palmitate (VAP) encapsulation was determined. VAP was successfully loaded into the particles by solvent-free method. The arrangement of spatial structure made cyclodextrin molecular cavity encapsulation in ß-CD-POF(I) more stable for VAP capture than that of KOH-ß-CD-MOF.

ß-Cyclodextrin/chitosan-based (polyvinyl alcohol-co-acrylic acid) interpenetrating hydrogels for oral drug delivery.

Gallic acid is an important phenolic compound with extensive applications in the food and pharmaceutical industries due to its health-promoting properties. However, due to its poor solubility and bioavailability, it is rapidly excreted from the body. Therefore, ß-cyclodextrin/chitosan-based (polyvinyl alcohol-co-acrylic acid) interpenetrating controlled release hydrogels were developed to improve its dissolution and bioavailability. pH, polymer ratios, dynamic and equilibrium swelling, porosity, sol-gel, FTIR, XRD, TGA, DSC, SEM and structural parameters like an average molecular weight between crosslinks, solvent interaction parameters, and diffusion coefficient affecting release behavior were investigated. The highest swelling and release were observed at pH 7.4. Furthermore, hydrogels showed good antioxidant and antibacterial properties. Hydrogels improved the bioavailability of gallic acid in a pharmacokinetics study in rabbits. In vitro biodegradation showed that hydrogels were more stable in blank PBS than lysozyme and collagenase. Hydrogels were safe for rabbits (3500 mg/kg) without causing hematological or histopathological changes. The hydrogels showed good biocompatibility, and no adverse reactions were observed. Moreover, the developed hydrogels can be used to improve the bioavailability of various other drugs.

Ellagic Acid Inclusion Complex-Loaded Hydrogels as an Efficient Controlled Release System: Design, Fabrication and In Vitro Evaluation.

Oxidants play a crucial role in the development of oxidative stress, which is linked to disease progression. Ellagic acid is an effective antioxidant with applications in the treatment and prevention of several diseases, since it neutralizes free radicals and reduces oxidative stress. However, it has limited application due to its poor solubility and oral bioavailability. Since ellagic acid is hydrophobic, it is difficult to load it directly into hydrogels for controlled release applications. Therefore, the purpose of this study was to first prepare inclusion complexes of ellagic acid (EA) with hydroxypropyl-ß-cyclodextrin and then load them into carbopol-934-grafted-2-acrylamido-2-methyl-1-propane sulfonic acid (CP-g-AMPS) hydrogels for orally controlled drug delivery. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to validate ellagic acid inclusion complexes and hydrogels. There was slightly higher swelling and drug release at pH 1.2 (42.20% and 92.13%) than at pH 7.4 (31.61% and 77.28%), respectively. Hydrogels had high porosity (88.90%) and biodegradation (9.2% per week in phosphate-buffered saline). Hydrogels were tested for their antioxidant properties in vitro against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Additionally, the antibacterial activity of hydrogels was demonstrated against Gram-positive bacterial strains (Staphylococcus aureus and Escherichia coli) and Gram-negative bacterial strains (Pseudomonas aeruginosa).

Cellulose nanocrystalline from biomass wastes: An overview of extraction, functionalization and applications in drug delivery.

Cellulose nanocrystals (CNC) have been extensively used in various fields due to their renewability, excellent biocompatibility, large specific surface area, and high tensile strength. Most biomass wastes contain significant amounts of cellulose, which forms the basis of CNC. Biomass wastes are generally made up of agricultural waste, and forest residues, etc. CNC can be produced from biomass wastes by removing the non-cellulosic components through acid hydrolysis, enzymatic hydrolysis, oxidation hydrolysis, and other mechanical methods. However, biomass wastes are generally disposed of or burned in a random manner, resulting in adverse environmental consequences. Hence, using biomass wastes to develop CNC-based carrier materials is an effective strategy to promote the high value-added application of biomass wastes. This review summarizes the advantages of CNC applications, the extraction process, and recent advances in CNC-based composites, such as aerogels, hydrogels, films, and metal complexes. Furthermore, the drug release characteristics of CNC-based material are discussed in detail. Additionally, we discuss some gaps in our understanding of the current state of knowledge and potential future directions of CNC-based materials.

Study of Hydroxypropyl ß-Cyclodextrin and Puerarin Inclusion Complexes Encapsulated in Sodium Alginate-Grafted 2-Acrylamido-2-Methyl-1-Propane Sulfonic Acid Hydrogels for Oral Controlled Drug Delivery.

Puerarin has been reported to have anti-inflammatory, antioxidant, immunity enhancement, neuroprotective, cardioprotective, antitumor, and antimicrobial effects. However, due to its poor pharmacokinetic profile (low oral bioavailability, rapid systemic clearance, and short half-life) and physicochemical properties (e.g., low aqueous solubility and poor stability) its therapeutic efficacy is limited. The hydrophobic nature of puerarin makes it difficult to load into hydrogels. Hence, hydroxypropyl-ß-cyclodextrin (HP-ßCD)-puerarin inclusion complexes (PIC) were first prepared to enhance solubility and stability; then, they were incorporated into sodium alginate-grafted 2-acrylamido-2-methyl-1-propane sulfonic acid (SA-g-AMPS) hydrogels for controlled drug release in order to increase bioavailability. The puerarin inclusion complexes and hydrogels were evaluated via FTIR, TGA, SEM, XRD, and DSC. Swelling ratio and drug release were both highest at pH 1.2 (36.38% swelling ratio and 86.17% drug release) versus pH 7.4 (27.50% swelling ratio and 73.25% drug release) after 48 h. The hydrogels exhibited high porosity (85%) and biodegradability (10% in 1 week in phosphate buffer saline). In addition, the in vitro antioxidative activity (DPPH (71%), ABTS (75%), and antibacterial activity (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) indicated the puerarin inclusion complex-loaded hydrogels had antioxidative and antibacterial capabilities. This study provides a basis for the successful encapsulation of hydrophobic drugs inside hydrogels for controlled drug release and other purposes.