Development and characterization of pH-responsive Delonix regia/mucin co-poly (acrylate) hydrogel for controlled drug delivery of metformin HCl.

This study introduces a pH-responsive hydrogel developed from Delonix regia and mucin co-poly(acrylate) through free radical polymerization to enhance controlled drug delivery systems. Characterization using FTIR, DSC, TGA, SEM, PXRD, and EDX spectroscopy detailed the hydrogel's amorphous and crystalline structures, thermal stability, surface characteristics, and elemental composition. Tested at a pH of 7.4-mimicking intestinal conditions-the hydrogel demonstrated significant swelling, indicating its capability for targeted drug release. With Metformin HCl as a model drug, the hydrogel exhibited a promising sustained release profile, underscoring its potential for oral administration. Safety and biocompatibility were assessed through acute oral toxicity studies in albino rabbits, encompassing biochemical, hematological, and histopathological evaluations. X-ray imaging confirmed the hydrogel's navigability through the gastrointestinal tract, affirming its application in drug delivery. By potentially mitigating gastrointestinal side effects, enhancing patient compliance, and improving therapeutic efficacy, this Delonix regia/mucin co-poly(acrylate) hydrogel represents a step in pharmaceutical sciences, exploring innovative materials and methodologies for drug delivery.

Development and evaluation of a pH-responsive Mimosa pudica seed mucilage/ß- cyclodextrin-co-poly(methacrylate) hydrogel for controlled drug delivery: In vitro and in vivo assessment.

In this comprehensive investigation, a novel pH-responsive hydrogel system comprising mimosa seed mucilage (MSM), ß-cyclodextrin (ß-CD), and methacrylic acid (MAA) was developed via free radical polymerization technique to promote controlled drug delivery. The hydrogel synthesis involved strategic variations in polymer, monomer, and crosslinker content in fine-tuning its drug-release properties. The resultant hydrogel exhibited remarkable pH sensitivity, selectively liberating the model drug (Capecitabine = CAP) under basic conditions while significantly reducing release in an acidic environment. Morphological, thermal, and structural analyses proved that CAP has a porous texture, high stability, and an amorphous nature. In vitro drug release experiments showcased a sustained and controlled release profile. Optimum release (85.33 %) results were recorded over 24 h at pH 7.4 in the case of MMB9. Pharmacokinetic evaluation in healthy male rabbits confirmed bioavailability enhancement and sustained release capabilities. Furthermore, rigorous toxicity evaluations and histopathological analyses ensured the safety and biocompatibility of the hydrogel. This pH-triggered drug delivery system can be a promising carrier system for drugs involving frequent administrations.

Quince seed mucilage/ß-cyclodextrin/Mmt-Na+-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine.

In current work, quince seed mucilage and ß-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 µg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

Formulation of pH-responsive highly swellable hydrogel scaffolds for controlled release of tramadol HCl: characterization and biocompatibility evaluation.

Introduction: The objective of current project was to formulate a system for controlled delivery of Tramadol HCl (TRD), an opioid analgesic used in the treatment of moderate to severe pain. Methods: For this purpose, a pH responsive AvT-co-poly hydrogel network was formulated through free radical polymerization by incorporating natural polymers i.e., aloe vera gel and tamarind gum, monomer and crosslinker. Formulated hydrogels were loaded with Tramadol HCl (TRD) and evaluated for percent drug loading, sol-gel fraction, dynamic and equilibrium swelling, morphological characteristics, structural features and in-vitro release of Tramadol HCl. Results and Discussions: Hydrogels were proved to be pH sensitive as remarkable dynamic swelling response ranging within 2.94g/g-10.81g/g was noticed at pH 7.4 as compared to pH 1.2. Percent drug loading was in the range of 70.28%-90.64% for all formulations. Thermal stability and compatibility of hydrogel components were validated by DSC analysis and FTIR spectroscopy. Controlled release pattern of Tramadol HCl from the polymeric network was confirmed as maximum release of 92.22% was observed for over a period of 24 hours at pH 7.4. Moreover, oral toxicity studies were also conducted in rabbits to investigate the safety of hydrogels. No evidence of any toxicity, lesions and degeneration was reported, confirming the biocompatibility and safety of grafted system.

Development of Tofacitinib Loaded pH-Responsive Chitosan/Mucin Based Hydrogel Microparticles: In-Vitro Characterization and Toxicological Screening.

Tofacitinib is an antirheumatic drug characterized by a short half-life and poor permeability, which necessitates the development of sustained release formulation with enhanced permeability potential. To achieve this goal, the free radical polymerization technique was employed to develop mucin/chitosan copolymer methacrylic acid (MU-CHI-Co-Poly (MAA))-based hydrogel microparticles. The developed hydrogel microparticles were characterized for EDX, FTIR, DSC, TGA, X-ray diffraction, SEM, drug loading; equilibrium swelling (%), in vitro drug release, sol-gel (%) studies, size and zeta potential, permeation, anti-arthritic activities, and acute oral toxicity studies. FTIR studies revealed the incorporation of the ingredients into the polymeric network, while EDX studies depicted the successful loading of tofacitinib into the network. The thermal analysis confirmed the heat stability of the system. SEM analysis displayed the porous structure of the hydrogels. Gel fraction showed an increasing tendency (74-98%) upon increasing the concentrations of the formulation ingredients. Formulations coated with Eudragit (2% w/w) and sodium lauryl sulfate (1% w/v) showed increased permeability. The formulations equilibrium swelling (%) increased (78-93%) at pH 7.4. Maximum drug loading and release (%) of (55.62-80.52%) and (78.02-90.56%), respectively, were noticed at pH 7.4, where the developed microparticles followed zero-order kinetics with case II transport. Anti-inflammatory studies revealed a significant dose-dependent decrease in paw edema in the rats. Oral toxicity studies confirmed the biocompatibility and non-toxicity of the formulated network. Thus, the developed pH-responsive hydrogel microparticles seem to have the potential to enhance permeability and control the delivery of tofacitinib for the management of rheumatoid arthritis.

Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine.

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. Sodium carboxymethyl cellulose (Na-CMC) and pectin were cross-linked chemically with methacrylic acid (MAA) as a monomer, using methylene bisacrylamide (MBA) as cross-linker and ammonium per sulfate (APS) as an initiator. Prepared hydrogel formulations were characterized for their texture, morphology, cytarabine loading efficiency, compositional and structural properties, thermal nature, stability, swelling response, drug release profile (pH 1.2 and pH 7.4), and in-vivo pharmacokinetic evaluation. Cytarabine-loaded hydrogels were also evaluated for their safety profile by carrying out toxicity studies in rabbits. Results demonstrated efficient encapsulation of cytarabine into the prepared network with loading ranging from 48.5-82.3%. The highest swelling ratio of 39.38 and maximum drug release of 83.29-85.27% were observed at pH 7.4, highlighting the pH responsiveness of the grafted system. Furthermore, cytarabine maximum release was noticed over 24 h, ensuring a sustained release response for all formulations. Histopathological studies and hemolytic profiles confirmed that the prepared hydrogel system was safe, biocompatible, and non-irritant, showing no symptoms of any toxicities and degeneration in organs. Moreover, pharmacokinetic estimation of the cytarabine-loaded hydrogel showed a remarkable increase in the plasma half-life from 4.44 h to 9.24 h and AUC from 22.06 µg/mL.h to 56.94 µg/mL.h. This study revealed that the prepared hydrogel carrier system has excellent abilities in delivering the therapeutic moieties in a controlled manner.

pH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies.

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45-83.54% and 50.13-72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

Synthesis and evaluation of chitosan based controlled release nanoparticles for the delivery of ticagrelor.

The aim of this contemporary work was to formulate a controlled release mucoadhesive nanoparticle formulation for enhancing the oral bioavailability of Ticagrelor (TG), a BCS class IV drug, having low oral bioavailability of about 36%. The nanoparticles can act as efficient carriers for hydrophobic drugs, due to having high surface area and hence can improve their aqueous solubility due to their hydrophilic nature. The nanoparticles (NPs) of TG were formulated using chitosan (CH) as polymer and sodium tripolyphosphate (TPP) as cross-linker, by ionic gelation technique with varying concentrations of polymer with respect to TG and TPP. Characterization of prepared nanoparticles was carried out to assess zeta potential, size, shape, entrapment efficiency (EE) and loading capacity (LC), using zeta sizer, surface morphology and chemical compatibility analysis. Drug release was observed using UV-Spectrophotometer. By increasing concentration of CH the desired size of particles (106.9 nm), zeta potential (22.6 mv) and poly dispersity index (0.364) was achieved. In vitro profiles showed a controlled and prolonged release of TG in both lower pH-1.2 and neutral pH-7.4 mediums, with effective protection of entrapped TG in simulated gastric conditions. X-ray diffraction patterns (XRD) showed the crystalline nature of formed NPs. Hence, this effort showed that hydrophobic drugs can be effectively encapsulated in nanoparticulate systems to enhance their solubility and stability, ultimately improving their bioavailability and effectiveness with better patient compliance by reducing dosing frequencies as well.

Biocompatible polymeric blend for pH driven delivery of cytarabine: Effect of feed contents on swelling and release kinetics.

Purpose of this study was to prepare chitosan/tamarind crosslinked poly (methacrylic acid) hydrogels for pH responsive delivery of cytarabine by using aqueous free radical polymerization technique. Polymers were chemically cross-linked with monomer (methacrylic acid) using methylene bisacrylamide as cross-linking agent and ammonium per sulphate as a reaction initiator in aqueous medium. Developed hydrogels were characterized for morphology, physical existence, drug loading (%), compositional and structural analysis, thermal behavior and stability, drug release analysis (pH 1.2 and pH 7.4), and in vivo release kinetics. pH sensitive behavior was established by observing swelling and release behavior at different pH values (1.2 and 7.4). Biocompatibility of network was evaluated through acute oral toxicity studies in rabbits. Results revealed that cytarabine was efficiently loaded in prepared hydrogels with an entrapment efficiency of 54.67%-108.59%. Highest swelling ratio of 38.67 was noticed at pH 7.4. Maximum pH sensitive behavior was seen at pH 7.4 showing maximum drug release up to 94.51%. All developed formulations followed zero order release as confirmed from regression coefficient (R2  = 0.9912-0.9991). In-vivo studies confirmed enhanced bioavailability of cytarabine. Histopathological examination and hemocompatibility studies proved that developed hydrogel system was safe, biocompatible, nonhemolytic in nature exhibiting no symptoms of dermal, ocular toxicities, and no changes in biochemical parameters of blood and histology of key organs. So, developed hydrogel system can be employed as an excellent drug delivery device where controlled drug delivery is desired.

In vitro phytochemical and anticancer activity of Misopates orontium L. and Dicliptera bupleuroides Nees.

In the present study phytochemical analysis and anticancer activity of Misopates orontium L. and Dicliptera bupleuroides Nees was carried out. Methanolic extracts of M. orontium and D. bupleuroides were selected for phytochemical analysis. The present analysis showed the presence of phytochemical such as carbohydrates, proteins, tannins, glycosides, alkaloids, saponins, phenols and flavonoids in M. orontium and D. bupleuroides. Anticancer assays including MTT, Alamar Blue (AB), Neutral Red (NR) and lactate dehydrogenase (LDH) were employed on whole herb methanolic extract and all other fractions of both plants to calculate the % age of cell viability and cell cytotoxicity. The percentage of cell viability was highly significant in all anticancer assays for all fractions. Therefore, ethyl acetate and aqueous fractions showed the excellent profile in evaluation of cytotoxicity in each assay. All above findings indicated that the whole herb of both selected plants have strong anticancer activity.

Smart pH-responsive Co-polymeric Hydrogels for Controlled Delivery of Capecitabine: Fabrication, Optimization and In Vivo Toxicology Screening.

BACKGROUND: Despite exhibiting promising anticancer potential, the clinical significance of capecitabine (a potent prodrug of 5-fluorouracil used for the treatment of colorectal cancer) is limited owing to its acidic and enzymatic hydrolysis, lower absorption following the oral administration, poor bioavailability, short plasma half-life, and poor patient compliance. OBJECTIVES: The present study was aimed to fabricate the capecitabine as a smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media. METHODS: The smart pH-sensitive HP-ß-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination. RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. The range of capecitabine loading was from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%)was seen at pH 7.4. Based upon regression coefficient R2(0.96 - 0.99) the best-fit model was zero-order. The extensive toxicity evaluations evidenced a good safety profile with no signs of oral, dermal, or ocular toxicities, as well as no variations in blood parameters and histology of vital organs. CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as a pH-responsive system for the controlled delivery of anticancer agents.