Delivery Of Sodium Research Articles

Development and optimization of hydrogel-forming microneedles fabricated with 3d-printed molds for enhanced dermal diclofenac sodium delivery: a comprehensive in vitro, ex vivo, and in vivo study.

With the developing manufacturing technologies, the use of 3D printers in microneedle production is becoming widespread. Hydrogel-forming microneedles (HFMs), a variant of microneedles, demonstrate distinctive features such as a high loading capacity and controlled drug release. In this study, the conical microneedle master molds with approximately 500μm needle height and 250μm base diameter were created using a Stereolithography (SLA) 3D printer and were utilized to fabricate composite HFMs containing diclofenac sodium. Using Box-Behnken Design, the effects of different polymers on swelling index and mechanical strength of the developed HFMs were evaluated. The optimum HFMs were selected according to experimental design results with the aim of the highest mechanical strength with varying swelling indexes, which was needed to use 20% Gantrez S97 and 0.1% (F22), 0.42% (F23), and 1% (F24) hyaluronic acid. The skin penetration and drug release properties of the optimum formulations were assessed. Ex vivo studies were conducted on formulations to determine drug penetration and accumulation. F24, which has the highest mechanical strength and optimized swelling index, achieved the highest drug accumulation in the skin tissue (17.70 ± 3.66%). All optimum HFMs were found to be non-cytotoxic by the MTT cell viability test (> 70% cell viability). In in vivo studies, the efficacy of the F24 was assessed for the treatment of xylene-induced ear edema by contrasting it to the conventional dosage form. It was revealed that HFMs might be an improved replacement for conventional dosage forms in terms of dermal diseases such as actinic keratosis.

Preparation and Characterization of Biopolymeric Hybrid Microbeads for Controlled Drug Delivery of Levothyroxine Sodium

Preparation and Characterization of Biopolymeric Hybrid Microbeads for Controlled Drug Delivery of Levothyroxine Sodium

Acetazolamide Therapy and Kidney Function in Persons with Nonalbuminuric Diabetes Mellitus Type 1.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. Methods: We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. Results: The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (< 3.5 mEq/L) were observed. Conclusions: Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

PH-RESPONSIVE INTERPENETRATING POLYMER NETWORK HYDROGEL MICROBEADS OF POLYACRYLAMIDE-G-GUM KONDAGOGU AND SODIUM ALGINATE FOR GASTROPROTECTIVE DRUG DELIVERY: IN VITRO-IN VIVO CHARACTERIZATIONS

The present work aims to design interpenetrating polymer network (IPN) mediated hydrogel microbeads of hydrolyzed polyacrylamide-g-gum kondagogu (H-pAAm-g-GK) and sodium alginate (SA) for pH-sensitive gastroprotective drug delivery of diclofenac sodium (DS). In brief, the pAAm-g-GK was prepared using microwave irradiation, followed by conversion into a pH-sensitive polymer (H-pAAm-g-GK) using alkaline hydrolysis. Then, DS-loaded IPN microbeads were made utilizing an ionotropic gelation method using Ca+2 ions and glutaraldehyde (GA) as a crosslinking agent. After this, different characterizations, such as FT-IR, DSC, PXRD, swelling analysis, drug entrapment, drug release study, in vivo anti-inflammatory activity, etc., were performed. The amorphous state of DS in the microbeads was validated by thermograms and diffractograms, whereas SEM analysis confirmed the spherical shape of the obtained DS-loaded H-pAAm-g-GK@SA mediated microbeads. The pulsatile swelling analysis assured the H-pAAm-g-GK@SA mediated microbeads showed significantly increased swelling as the pH switched from 1.2 to 7.4. Additionally, the microbeads exhibit a 15% DS release in a pH 1.2 buffer medium, while a substantial 94% of the drug was released in a pH 7.4 buffer. It assured the DS release was drastically augmented as the pH of the surrounding medium was switched from acidic to alkaline. Principally, the COOH- groups of hydrogels offer ionization at higher pH levels, wherein the osmotic pressure within the microbeads rises, resulting in more swelling and higher drug release. Finally, the in vivo anti-inflammatory activity assured pH-sensitive sustained release of DS. In conclusion, the H-pAAm-g-GK@SA mediated pH-sensitive IPN hydrogel microbeads show potential in the design of gastroprotective oral delivery systems for DS. In the future, H-pAAm-g-GK can be used for the design of pH-sensitive IPN hydrogel microbeads for targeted delivery.

Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma.

This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, in vitro drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and in vitro release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by in vitro cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.

Enhanced diclofenac sodium delivery through advanced self-microemulsifying pectin-based transdermal patches

Diclofenac sodium (DCFNa) presents significant challenges in local pain relief due to its poor solubility and limited skin permeability. This study aimed to enhance the solubility and skin permeation of DCFNa by developing DCFNa-loaded self-microemulsifying drug delivery system (SMEDDS) embedded pressure-sensitive adhesive (PSA) patch. The solubility of DCFNa in various solvents was evaluated, and a ternary phase diagram was constructed to optimize the SMEDDS formulation. The transdermal patch, composed of pectin and polyacrylate, was optimized using a simplex lattice experimental design to achieve the desired adhesion strength and to select the most suitable patch for skin drug accumulation study. Clove oil, Tween® 80, and propylene glycol were identified as the appropriate oil, surfactant, and co-surfactant, respectively, for achieving highest DCFNa solubility. The SMEDDS was formed with a ratio of 5:35:60 (oil: Smix [1:1 surfactant: co-surfactant]: water), yielding nano-sized droplets (22.64 ± 0.74 nm) and significantly enhancing DCFNa solubility (329.62 ± 10.16 mg/mL) compared to phosphate buffer (5.03 ± 1.01 mg/mL). The DCFNa-loaded SMEDDS demonstrated a 9-fold increase in skin permeability compared to the DCFNa solution. The optimized PSA patch, containing 20 % pectin and 40 % polyacrylate, exhibited superior tacking and peel strength. Additionally, a 1 % DCFNa-loaded SMEDDS patch delivered twice greater drug accumulation in the skin and showed no skin irritation, maintaining better adhesion for up to 24 h compared to commercial patches.

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management.

Oral delivery of sodium alginate/chitosan bilayer microgels loaded with Lactobacillus rhamnosus GG for targeted therapy of ulcerative colitis

Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

Myriad of factors involved in blood pressure control. Salt intake connects them all.

Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.

Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2

The renal epithelium is sensitive to changes in blood potassium (K+). We identify the basolateral K+ channel, Kir4.2, as a mediator of the proximal tubule response to K+ deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K+ depletion, knockout animals decompensate as evidenced by increased urinary K+ excretion and development of a proximal renal tubular acidosis. Potassium wasting is not proximal in origin but is caused by higher ENaC activity and depends upon increased distal sodium delivery. Three-dimensional imaging reveals Kir4.2 knockouts fail to undergo proximal tubule expansion, while the distal convoluted tubule response is exaggerated. AKT signaling mediates the dietary K+ response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K+ depends upon mTORC2 activation by secondary changes in Cl- transport. Data support a proximal role for cell Cl- which, as it does along the distal nephron, responds to K+ changes to activate kinase signaling.

Luminal flow-stimulated superoxide participates in connecting tubule-glomerular feedback

Increasing NaCl concentration in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art) through the connecting tubule-glomerular feedback (CNTGF). CNTGF is mediated by Na+ transport via epithelial Na+ channels (ENaC) in the CNT. It is unknown if CNTGF is mainly activated by NaCl concentration or sodium delivery or if there is an independent luminal flow effect. Previous studies showed that luminal flow stimulates superoxide (O2−), and O2− can activate ENaC. Thus we hypothesized that increasing luminal flow in the CNT induces CNTGF via O2− generation and ENaC activation. Rabbit Af-Arts with the adjacent CNTs were microdissected and perfused in vitro. Protocols consist of two consecutive dose-response curves to flow rate in the same preparation. When the CNT was perfused with 5mM NaCl, increasing flow rates from 5 to 10, 20, and 40 nL/min caused flow rate-dependent Af-Art dilatation (p<0.01). Adding an ENaC blocker benzamil to the perfusate blocked flow-induced Af-Art dilatation, indicating a CNTGF response. Using mathematical modeling, an increased tubular flow controlled by NaCl delivery into the CNT independently increases CNTGF vasodilation. However, when CNT was perfused with 0 mM NaCl, increasing the flow rate did not induce CNTGF vasodilation. The O2− dismutase mimetic tempol reduced flow-induced CNTGF. In the presence of L-NAME (NOS inhibitor), the reduced CNTGF mediated by tempol was unaffected. We concluded that increasing luminal flow in CNT induces CNTGF activation via ENaC, partly due to flow-stimulated O2− production and independently of NOS. 1K01HL155235. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oxidative Coupling Assembly Induced Bio-engineered Quercetin Microspheres for the Gastrosparing Delivery of Diclofenac Sodium.

The study aimed to develop microspheres of quercetin by oxidative coupling assembly and these microspheres were used to deliver diclofenac sodium without causing gastrotoxicity. The oxidative coupling assembly of quercetin was carried out in the presence of copper sulfate to yield quercetin microspheres. The microsphere of quercetin was loaded with diclofenac sodium (QP-Diclo). The carrageenan induced paw edema in rats was used for anti-inflammatory action was studied by using and acetic acid-induced writhing in mice was used to study the analgesic potential of the QP loaded microspheres. The ulcerogenecity and gastrotoxicity comparison was made between diclofenac and QP-Diclo. The oxidative coupling assembly of quercetin resulted in microspheres of 10-20 μm in size, which were loaded with diclofenac sodium (QP-Diclo). The marked anti-inflammatory activity was observed by QP-Diclo treatment using carrageenan induced paw edema (in rats) and better analgesic activity than diclofenac sodium in mice. The administration of QP-Diclo significantly elevated the diminished overall nitrite/nitrate extent and thiobarbituric acid reactive and significantly increased the diminished superoxide dismutase activity in comparison to diclofenac sodium in gastric mucosa. The results suggested that dietary polyphenol quercetin can be converted to microspheres by oxidative coupling assembly and can be used to deliver diclofenac sodium without causing gastrotoxicity.

The Proximal Tubule Response to Low Potassium Is Mediated by mTOR/AKT Activation via Kir4.2

Background: The renal epithelium is highly sensitive to changes in blood potassium (K+) levels. We have a detailed understanding of distal K+-sensitive signaling pathways, yet proximal mechanisms are less well-defined. Results: Mice lacking the basolateral proximal tubule inwardly rectifying K+ channel, Kir4.2, (Kir4.2−/−) demonstrated normal blood and urine electrolytes at baseline. Upon removal of K+ from their diet, Kir4.2−/− animals decompensated as evidenced by increased urinary K+ excretion and development of a proximal renal tubular acidosis compared to control animals (Kir4.2+/+). Potassium wasting in Kir4.2−/− mice was not proximal in origin, but was dependent upon increased ENaC activity along the connecting segment. This was demonstrated by the correction of K+ wasting in knockouts treated with the ENaC inhibitor, amiloride. Using lithium clearance studies, we further demonstrated increased distal sodium delivery in Kir4.2−/− animals due to reduced proximal tubule sodium reabsorption. Optical clearing and three-dimensional confocal imaging reveal Kir4.2−/− mice failed to undergo proximal tubule hypertrophy when fed a low K+ diet, while the distal convoluted tubule response was exaggerated in knockouts compared to control animals. A phosphoproteomics mass spectrometry analysis identified increased mTOR/AKT signaling as mediating the proximal dietary response to K+ depletion in control animals, and changes to mTOR/AKT signaling was blunted in Kir4.2 knockouts. Lastly, we demonstrated in isolated renal tubules that AKT phosphorylation in response to low K+ depended upon mTORC2 activation by secondary reductions in intracellular Cl−. Conclusions: In this work we identify the basolateral inwardly rectifying K+ channel, Kir4.2, as a mediator of the proximal tubule response to K+ deficiency. Kir4.2 knockout mice increase their distal nephron transport burden to maintain electrolyte homeostasis in the face of deficient proximal tubule cell function. Data identify a conserved proximal role for cell Cl− which, as it does along the distal convoluted tubule, responds to extracellular K+ changes to activate intracellular kinase signaling. Along the proximal tubule, mTOR/AKT signaling is essential for the cell response to low K+. Proximal and distal nephron cell Cl− responses work in concert to preserve K+ homeostasis. These studies were supported by NIH grants DP5-OD033412 (AST), DK51265, DK95785, DK62794, DK7569, P30DK114809 (RCH, MZZ), and the Vanderbilt Center for Kidney Disease and Vanderbilt Diabetes Research and Training Center (DK020593) pilot and feasibility grant (JSD). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficient drug delivery potential and antimicrobial activity of biocompatible hydrogels of dextrin/Na-alginate/PVA

Ceftriaxone sodium belongs to the third-generation cephalosporin group and is used intramuscular and intravenous route as a broad-spectrum antibiotic. This research aims to prepare biocompatible hydrogels for targeted delivery of ceftriaxone sodium by parental route. Different proportions of polymers (natural and synthetic) in the presence of cross-linker were synthesized by solvent casting method. Ceftriaxone sodium was loaded in hydrogels in different concentrations and its drug release behavior was evaluated along with swelling and biodegradation analysis. The characterization of hydrogel was done by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) to analyze surface morphology and functional groups involved in the formation of dextrin/Na-alginate/PVA hydrogels loaded with the drug. Thermogravimetric analysis (TGA) was confirmed by thermal stability and degradation pattern of loaded and unloaded hydrogels. The drug-loaded samples presented promising antimicrobial activity against S. aureus and P. multocida and their cytotoxic nature was also studied. Drug release analysis using simulated intestinal fluid (SIF) and phosphate buffer saline(PBS) for the circulatory system shows the consistent release of the drug. The findings unveiled the development of a biocompatible and innovative hydrogel, which has potential advantages for biomedical application, particularly in enhancing the therapeutic efficacy of ceftriaxone sodium drug.

A Novel Approach of Polyvinyl Alcohol/Acrylic Acid Based Hydrogels for Controlled Delivery of Diclofenac Sodium.

The aim of this study was to prepare polyvinyl alcohol/acrylic acid (PVA/AA) hydrogels for the controlled release of diclofenac sodium and to develop PVA/AA hydrogels as controlled release carriers to overcome not only the side effects of diclofenac sodium but also sustain its release for an extended period. Diclofenac sodium is employed for relieving pain and fever. The half-life of diclofenac sodium is very short (1-2 h). Hence, multiple intakes of diclofenac sodium are required to maintain a constant pharmacological action. Multiple GI adverse effects are produced as a result of diclofenac sodium intake. A free radical polymerization technique was used for crosslinking PVA with AA in the presence of APS. EGDMA was used as a cross-linker. FTIR and XRD confirmed the preparation and loading of the drug by prepared hydrogels. An increase in the thermal stability of PVA was shown by TGA and DSC analysis. Surface morphology was investigated by SEM. Similarly, water penetration and drug loading were demonstrated by porosity and drug loading studies. The pH-sensitive nature of PVA/AA hydrogels was investigated at different pH values by swelling and drug release studies. The development and drug loading of PVA/AA hydrogels were confirmed by FTIR and XRD analysis. TGA and DSC indicated high thermal stability of prepared hydrogels as compared to unreacted PVA. SEM indicated a hard and compact network of developed hydrogels. The swelling and drug release studies indicated maximum swelling and drug release at high pH as compared to low pH values, indicating the pH-sensitive nature of prepared hydrogels. Moreover, we demonstrated that drug release was sustained for a prolonged time in a controlled pattern by prepared hydrogels by comparing the drug release of the developed hydrogels with the commercial product Cataflam. The results indicated that prepared PVA/AA hydrogels can be used as an alternative approach for the controlled delivery of diclofenac sodium.

DIFUCOSIN: DIclofenac sodium salt loaded FUCOidan-SericIN nanoparticles for the management of chronic inflammatory diseases

The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1β with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.

Quality by Design Enabled Formulation Optimization of Rabeprazole Sodium Mucoadhesive Microcapsules for the Treatment of Gastroesophageal Reflux Disease

Aims: The present research describes the implementation of quality by-design principles for developing the mucoadhesive microcapsules of rabeprazole sodium for treating gastroesophageal reflux disease conditions. Background: In addition, a holistic QbD-based product development strategy was implemented, where the target product profile was defined based on desired product quality of mucoadhesive microcapsules. Based on TPP, the critical quality attributes were identified. The identification of CMAs was carried out with the help of risk assessment and factor screening exercises, which indicated drugpolymer ratio (X1), temperature (X2), and stirring speed (X3) as the influential factors. Methods: The mucoadhesive microcapsules of rabeprazole sodium were prepared by a solvent evaporation method, and 33 Box-Behnken optimization design was used for the optimization of the selected factors, and mucoadhesive microcapsules formulations were evaluated for particle size (μm), drug entrapment efficiency (%), mucoadhesion (%), and in vitro drug release (Q18h) in percentage characteristics. Mathematical data analysis was performed to fit the two-factor interaction model, and optimized mucoadhesive microcapsules formulation was selected. Results: The optimized mucoadhesive microcapsules indicated desired formulation characteristics with smaller particle size, good entrapment efficiency, better mucoadhesion, and sustained drug release characteristics. Conclusion: In a nutshell, the studies vouch for the successful development of mucoadhesive microcapsules for oral delivery of rabeprazole sodium which could be used to manage gastroesophageal reflux disease condition.

Safety of ventricular arrhythmia radiofrequency ablation with half-normal saline irrigation.

Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15 Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.

Preparation and Evaluation of Diclofenac Sodium Loaded Liposomal Hydrogel in the Treatment of Rheumatoid Arthritis

In the present research, it was proposed to provide topical delivery of diclofenac sodium. Diclofenac sodium will be encapsulate in liposome and further loaded into a hydrogel and delivered through topical route. The lipid film hydration approach was used to create diclofenac sodium liposomes, which were then characterised by vesicle size, zeta potential, and entrapment effectiveness. The pH of the generated liposomal gels was within the permissible range of 7.0-7.2. The spreadability of the gels was assessed using slip and drag characteristics and was found to be between 10.45 and 12.32 gm.cm/sec. F1, F2, and F3 spreadabilities were determined to be 10.45±0.075,12.32±0.042 and 11.75±0.049 gm.cm/sec, respectively. The viscosities for F1, F2, and F3 were determined to be 1870±25 cps, 1895±33 cps, and 1875±21 cps, respectively. The percentage of cumulative medication (diclofenac sodium) released from F1, F2, and F3 liposomal gel formulations was 98.15%±17, 98.72%±2.4 and 96.27%±2.7 respectively.

Green Synthesis of pH-Responsive Metal-Organic Frameworks for Delivery of Diclofenac Sodium.

The current study developed a drug delivery system through the green chemistry-based synthesis of a biologically friendly metal-organic framework (bio-MOF) called Asp-Cu, which included copper ions and the environmentally friendly molecule L(+)-aspartic acid (Asp). For the first time, diclofenac sodium (DS) was loaded onto the synthesized bio-MOF simultaneously. The system's efficiency was then improved by encapsulating it with sodium alginate (SA). FT-IR, SEM, BET, TGA, and XRD analyses confirmed that DS@Cu-ASP was successfully synthesized. DS@Asp-Cu was found to release the total load within 2 h when used with simulated stomach media. This challenge was overcome by coating DS@Cu-ASP with SA (SA@DS@Cu-ASP). SA@DS@Cu-ASP displayed limited drug release at pH 1.2, and a higher percentage of the drug was released at pH 6.8 and 7.4 due to the pH-responsive nature of SA. In vitro cytotoxicity screening showed that SA@DS@Cu-ASP could be an appropriate biocompatible carrier with >90% cell viability. The on-command drug carrier was observed to be more applicable biocompatible with lower toxicity, as well as adequate loading properties and responsiveness, indicating its applicability as a feasible drug carrier with controlled release.