Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

BACKGROUND: Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. AIM: This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. METHODS: Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. RESULTS: Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. CONCLUSION: Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

Mucoadhesive, Fluconazole-Loaded Nanogels Complexed with Sulfhydryl-ß-cyclodextrin for Oral Thrush Treatment.

The objective of this study was to generate fluconazole-loaded mucoadhesive nanogels to address the problem of hydrophobicity of fluconazole (FL). An inclusion complex was formulated with sulfhydryl-ß-CD (SH-ß-CD) followed by nanogels formation by a Schiff base reaction of carbopol 940 (CA-940) and gelatin (GE). For characterization, PXRD, FT-IR analysis, drug content, and phase solubility studies were performed. Similarly, nanogels were assessed for particle size, zeta potential, organoleptic, and spreadability studies. Moreover, drug contents, rheological, in vitro drug permeation, release kinetics, toxicity, and stability studies of nanogels were performed. Furthermore, mucoadhesive characteristics over the buccal mucosal membrane of the goat were evaluated. The nanogels formulated with a higher amount of CA-940 and subsequently loaded with the inclusion complexes of FL showed promising results. PXRD and FT-IR analysis confirmed the physical complexes by displaying a reduction in the intensity of peaks of FL. The average particle size of nanogels was in the range of 257 to 361 nm. The highest drug content of 88% was encapsulated within the FL-SH-ß-CD complex. All formulations at 0.5-1% concentration displayed no toxicity to the Caco-2 cell lines. Nanogels loaded with FL-SH-ß-CD complexes showed 18-fold improved mucoadhesion on the buccal mucous membrane of the goat when compared to simple nanogels. The in vitro permeation study exhibited significantly enhanced permeation and first-order concentration-dependent drug release was observed. On the bases of these findings, we can conclude that a mucoadhesive nanogel-based drug delivery system can be an ideal therapy for candidiasis.

Mimosa pudica mucilage nanoparticles of losartan potassium: Characterization and pharmacodynamics evaluation.

The current research was to develop nanoparticles based on Mimosa pudica mucilage (MPM) that could encapsulate losartan potassium (LP). Nanoparticles (NPs) produced through ionic-gelation method; the polymerization of the mucilage carried out using calcium chloride as cross-linking agent. The MPMLP-NPs demonstrated vastly enhanced pharmaceutical characteristics, presented discrete surface with spherical shape of 198.4-264.6 nm with PDI ranging 0.326-0.461 and entrapment efficiency was in the range of 80.65 ± 0.82-90.79 ± 0.96%. FTIR and DSC indicated the stability of drug during the formulation of nanoparticles. An acute oral toxicity investigation found no significant alterations in behavior and histopathology criteria. The MPMLP-NPs formulation revealed the better rates and sustained effect as assessed with the commercial product. Moreover, low dose of MPMLP-NPs showed similar anti-hypertensive effect as assessed with the marketed tablet.

RP-HPLC method to assay ethinylestradiol and drospirenone with 3D chromatograph model in fixed dose in rat plasma for pharmacokinetic study analysis.

For the simultaneous measurement of Ethinylestradiol (EE) and Drospirenone (DP) in fixed-dose combination hormones tablets, a reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed. A specific, precise and accurate RP-HPLC method was developed and validated to analyse the drugs in rat plasma. The fluorescence detection for EE was made at λ= 200-310 nm and Ultraviolet-visible (UV/Vis) detection for DP was made at 270 nm. The typical EE and DP retention times were 4.19 and 5.30 minutes, respectively. The limit of detection (LOD) and limit of detection (LOQ) for EE were 0.121 and 0.282µg/mL and LOD and LOQ for DP were 2.23 and 7.697µg/mL respectively. The regression coefficient (r2) of EE and DP were 0.9937 and 0.9913 respectively. Precision's relative standard deviation (RSD) was less than 5%. The analyte recoveries of both drugs stayed within 95% of each other. All other validation parameters adhered to ICH standards. Throughout the analytical process, the analyte was stable. The advantages of the method developed include stability under different conditions and a low limit of quantification that was in micrograms. Its applicability was confirmed by the analysis of EE and DP levels in plasma samples in a designed pharmacokinetic study in rats after oral administration.

Control synthesis of mesoporous silica microparticles: Optimization and in vitro cytotoxicity studies.

The current paper explains how to make mesoporous silica microparticles (MSM) by mixing water and dichloromethane. Several dichloromethane-water ratios were used to adjust the reaction mixture for the first time to easily synthesize mesoporous silica micro particles with regulated particle size. By carefully modifying the concentrations of water and dichloromethane, a higher level of consistency was achieved in the production of micro particles, i.e. to a 2:1 v/v ratio. It was discovered that variations in the dichloromethane-to-water ratios significantly affect the surface roughness and morphologies of mesoporous silica particles along with size. This is most likely because the solvent affects how quickly tetraethyl orthosilicate (TEOS) and how quickly inorganic species polymerize. In all experiments, conditions were maintained the same at 25oC temperature and 1000 rpm. Scanner electron microscopy (SEM), Fourier transform infrared (FTIR) and X-ray powder diffraction (XRD) methods were used to identify the structure of MSM. The in vitro cytotoxicity assays showed that the produced particles, which had a diameter of 1.0 m, were safe for usage in the cellular system.

Nmnat3 deficiency in hemolytic anemia exacerbates malaria infection.

Malaria is an infectious disease caused by Plasmodium parasites and has high mortality rates, especially among children in African and Southeast Asian countries. Patients with hemolytic anemia are suggested to adapt protective measures against malarial infection. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor associated with numerous biological processes that maintain homeostasis in all living organisms. In a previous study, we had demonstrated that the deficiency of nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3), an enzyme catalyzing NAD+ synthesis, causes hemolytic anemia accompanied by a drastic decline in the NAD+ levels in the erythrocytes. It is well known that hemolytic anemia is linked to a reduced risk of malarial infections. In the present study, we investigated whether hemolytic anemia caused by Nmnat3 deficiency is beneficial against malarial infections. We found that Nmnat3 deficiency exacerbated malarial infection and subsequently caused death. Moreover, we demonstrated that the NAD+ levels in malaria-infected Nmnat3 red blood cells significantly increased and the glycolytic flow was largely enhanced to support the rapid growth of malarial parasites. Our results revealed that hemolytic anemia induced by the deletion of Nmnat3 was harmful rather than protective against malaria.

Computational design of a new multi-epitope vaccine using immunoinformatics approach against mastitis disease.

Mastitis disease causes significant economic losses in dairy farms by reducing milk production, increasing production costs, and reducing milk quality. Streptococcus agalactiae continues to be a major cause of mastitis in dairy cattle. To date, there has been no approved multi-epitope vaccine against this pathogen in the market. In the present study, an efficient multi-epitope vaccine against S. agalactiae, the causative agent of mastitis, was designed using various immonoinformtics approaches. Potential epitopes were selected from Sip protein to improve vaccine immunogenicity. The designed vaccine is more antigenic in nature. Then, linkers and profilin adjuvant were added to enhance the immunity of vaccines. The designed vaccine was evaluated in terms of molecular weight, PI, immunogenicity, Toxicity, and allergenicity. Prediction of three-dimensional (3 D) structure of multi-epitope vaccine, followed by refinement and validation, was conducted to obtain a high-quality 3 D structure of the designed multi-epitope vaccine. The designed vaccine was then subjected to molecular docking with Toll-like receptor 11 (TLR11) receptor to evaluate its binding efficiency followed by dynamic simulation for stable interaction. In silico cloning approach was carried out to improve the expression of the vaccine construct. These analyses indicate that the designed multi-epitope vaccine may produce particular immune responses against S. agalactiae and may be further helpful to control mastitis after in vitro and in vivo immunological assays.

Sol-Gel Synthesized High Entropy Metal Oxides as High-Performance Catalysts for Electrochemical Water Oxidation.

Hexanary high-entropy oxides (HEOs) were synthesized through the mechanochemical sol-gel method for electrocatalytic water oxidation reaction (WOR). As-synthesized catalysts were subjected to characterization, including X-ray diffraction (XRD), Fourier transforms infrared (FTIR) analysis, and scanning electron microscopy (SEM). All the oxide systems exhibited sharp diffraction peaks in XRD patterns indicating the defined crystal structure. Strong absorption between 400-700 cm-1 in FTIR indicated the formation of metal-oxide bonds in all HEO systems. WOR was investigated via cyclic voltammetry using HEOs as electrode platforms, 1M KOH as the basic medium, and 1M methanol (CH3OH) as the facilitator. Voltammetric profiles for both equiatomic (EHEOs) and non-equiatomic (NEHEOs) were investigated, and NEHEOs exhibited the maximum current output for WOR. Moreover, methanol addition improved the current profiles, thus leading to the electrode utility in direct methanol fuel cells as a sequential increase in methanol concentration from 1M to 2M enhanced the OER current density from 61.4 to 94.3 mA cm-2 using NEHEO. The NEHEOs comprising a greater percentage of Al, ([Al0.35(Mg, Fe, Cu, Ni, Co)0.65]3O4) displayed high WOR catalytic performance with the maximum diffusion coefficient, D° (10.90 cm2 s-1) and heterogeneous rate constant, k° (7.98 cm s-1) values. These primary findings from the EC processes for WOR provide the foundation for their applications in high-energy devices. Conclusively, HEOs are proven as novel and efficient catalytic platforms for electrochemical water oxidation.

Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls.

In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-ß [TGF-ß], and IL-10), and cytokine secretion levels (TGF-ß and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.

Analysis on International Competitiveness of Service Trade in the Guangdong-Hong Kong-Macao Greater Bay Area Based on Using the Entropy and Gray Correlation Methods.

Based on the analysis and measurement of the overall situation, import and export structure and international competitiveness of the various sectors of service trade in the Guangdong-Hong Kong-Macao Greater Bay Area, with the help of MATLAB and Gray System Modeling software, the synergy degree model was established to quantitatively analyze the synergy level of service trade in the Greater Bay Area with the help of grey correlation analysis method and entropy weight method. The results show that the overall development trend of service trade in the Guangdong-Hong Kong-Macao Greater Bay Area is good. The service trade industries in different regions are highly complementary and have a high degree of correlation. The potential for the coordinated development of internal service trade is excellent, and the overall situation of service trade in the Greater Bay Area is in a stage of transition from a moderate level of synergy to a high level of synergy. The Greater Bay Area can achieve industrial synergy by accelerating industrial integration and green transformation, establishing a coordinated development mechanism, sharing market platform, strengthening personnel security, and further enhancing the international competitiveness of service trade. The established model better reflects the current coordination of service trade in the Guangdong-Hong Kong-Macao Greater Bay Area and has good applicability. In the future, more economic, technological, geographic, and policy data and information can be comprehensively used to study the spatial pattern, evolution rules, and mechanisms of coordinated development in the broader area.

Phytochemical analysis, antioxidant and antibacterial potential of some selected medicinal plants traditionally utilized for the management of urinary tract infection.

Recent studies on prevalence of urinary tract infection indicate that approximately one third population of the world has been suffering from this disease. The current study was designed to evaluate the antibacterial activity of aqueous-ethanolic extracts (30/70) of Tribulus terrestris (TT), Vaccinium macrocarpon (VM), Cuminum cyminum (CC), Rheum emodi (RE), Piper cubeba (PC) and their compound formulation "Crano-cure" against Escherichia coli, Klebsiella pneumonia, Staphylococcus saprophyticus and Proteus mirabilis through disc diffusion method and agar well methods compared with standard Ciprofloxacin. DPPH radical scavenging methods were applied for antioxidant activities and phytochemical analysis was also performed to detect the phytoconstituents. All the plants exhibited potent antibacterial strength while Crano-cure showed most potent results comparable with that of standard drug. The zone of inhibition produced by disk diffusion test was 26±0.34, 26±0.75, 26±0.00, 18±0.64, 22.5±0.52, 29±0.39, 32±0.00 mm and for agar well diffusion test 23±0.67, 22±0.46, 23±0.77, 20±0.00, 22±0.46, 24±0.52, 33±0.00 mm against Tribulus terrestris, Cuminum cyminum, Rheum emodi, Piper cubeba, Vaccinium macrocarpon, crano-cure and ciprofloxacin. Similarly, percentage inhibition for antioxidant potential was 78.74, 24.57, 58.75, 20.23, 88.88, 90.12 and 92.35 respectively. The tested plants exhibited remarkable antibacterial and antioxidant activities.

An alternative approach to treat obesity with leptogenic polyherbal formulation obesecure: A randomized clinical trial study.

Obesity is a common disease of developing countries, including Pakistan. Obesity is a risk factor for many diseases which can be life threatening or making the person unable to perform daily routine work. In the current study, clinical trials were designed to evaluate the effects of medical intervention by comparing the effects of placebo control drug "Plasicure" with the herbal medicinal formulation "Obesecure". The test drug formulation was designed on the basis of the screening study for Leptogenic drugs. To evaluate the safety of the test drug, the toxicity index and the safety profile of test formulation was assessed on animal models. The drug was found safe for further clinical study. Randomized Controlled Clinical Trials were conducted. The statistical analysis was carried out by the application of Two-Way Repeated Analysis of Variance test. The clinical findings of randomized controlled trial revealed that the test drug was Leptogenic and effective in weight reduction as compared to control drug Plasicure therapy as the p-value deduced was 0.001 in leptin level and 0.000 in case of BMI after the conduction of Two-Way Repeated Analysis of Variance test. Hence it is concluded that obscure therapy is more significant than control drug Plasicure therapy in the management and treatment of obesity.

Synthesis and Characterization of Thiolated PVP-Iodine Complexes: Key to Highly Mucoadhesive Antimicrobial Gels.

The aim of this study was to synthesize iodine containing polymeric excipients for mucosal treatment of microbial infection exhibiting a prolonged mucosal residence time by forming an adhesive gel on the mucosal surface. In order to achieve this aim, 2-(2 acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinylpyrrolidone (NVP) to obtain thiolated polyvinylpyrrolidone (PVP) for complexation with iodine. The average molecular mass of different thiolated PVP variants was determined by size exclusion chromatography. The structure of thiolated PVP was confirmed by 1H NMR. Thiolated PVP variants were characterized for thiol content, cytotoxicity, iodine loading capacity, rheological behavior, and adhesion time on mucosa. The highest achieved degree of thiolation was 610 ± 43 µmol/g, and the maximum recorded iodine loading was 949 ± 31 µmol/g of polymer. Thiolated PVP variants (0.5% m/v) showed no toxicity after incubation on Caco-2 cells for the period of 3 and 24 h, respectively. Thiolated PVP and thiolated PVP-iodine complexes exhibited a 5.4- and 4.4-fold increased dynamic viscosity in porcine mucus in comparison to PVP and PVP-iodine complex, respectively. Compared to PVP and PVP-iodine complex thiol-functionalized PVP and PVP-iodine complexes demonstrated significantly prolonged attachment to mucosal surface over a period of 3 h. Thiol functionalized PVP proved to be a promising novel excipient for complexation with iodine and to exhibit strongly improved mucoadhesive properties.

Can thiolation render a low molecular weight polymer of just 20-kDa mucoadhesive?

The objective was to investigate whether even low-molecular weight polymers (LMWPs) can be rendered mucoadhesive due to thiolation. Interceded by the double catalytic system carbodiimide/N-hydroxysuccinimide, cysteamine was covalently attached to a copolymer, poly(4-styrenesulfonic acid-co-maleic acid) (PSSA-MA) exhibiting a molecular weight of just 20 kDa. Depending on the amount of added N-hydroxysuccinimide and cysteamine, the resulting PSSA-MA-cysteamine (PC) conjugates exhibited increasing degree of thiolation, highest being "PC 2300" exhibiting 2300.16 ± 149.86 µmol thiol groups per gram of polymer (mean ± SD; n = 3). This newly developed thiolated polymer was evaluated regarding mucoadhesive, rheological and drug release properties as well from the toxicological point of view. Swelling behavior in 100 mM phosphate buffer pH 6.8 was improved up to 180-fold. Furthermore, due to thiolation, the mucoadhesive properties of the polymer were 240-fold improved. Rheological measurements of polymer/mucus mixtures confirmed results obtained by mucoadhesion studies. In comparison to unmodified polymer, PC 2300 showed 2.3-, 2.3- and 2.4-fold increase in dynamic viscosity, elastic modulus and viscous modulus, respectively. Sustained release of the model drug codeine HCl out of the thiomer was provided for 2.5 h (p < 0.05), whereas the drug was immediately released from the unmodified polymer. Moreover, the thiomer was found non-toxic over Caco-2 cells for a period of 6- and 24-h exposure. Findings of the present study provide evidence that due to thiolation LMWPs can be rendered highly mucoadhesive as well as cohesive and that a controlled drug release out of such polymers can be provided.

MEDICAL EXPULSIVE TREATMENT OF DISTAL URETERAL STONE USING TAMSULOSIN.

BACKGROUND: Many minimally invasive interventional techniques as well as expectant treatment exist for the management of lower ureteric calculi. This study was conducted to evaluate th efficacy of tamsulosin as an expulsive pharmacologic therapy for the treatment of distal uretern stone. METHODS: This randomized control trial included 100 patients over 18 years of age wit stone Size > or = mm in distal 1/3 of ureter. Patients were randomly assigned into two groups (A & B Group A Patients were given Capsule Tamsulosin 0.4 mg, 1 daily up to 4 weeks while group B patients were given placebo, 1 Capsule daily up to 4 weeks. The primary endpoint was expulsio rate. A written informed consent was taken from all the patients. Expulsion time, need for analgesics, need for hospitalization and drug side effects were secondary endpoints. RESULTS: A total of 49 patients in group A and 48 patients in group B reported back, therefore 97 out of 10 patients were evaluated. Mean age of the patients was 36.34 years (range 18-57 years). Mea stone size was 5.78 mm (range 4-8 mm) in greatest dimension. A stone expulsion rate of 85.71C (42 patients) was noted in group A and 54.20% (26 patients) in group B. Group A revealed statistically significant advantage in term of stone expulsion rate (p=0.032). Considering expulsio time in days group A showed statistically significant advantage (p=0.015). Regarding age, se) stone size and stone lateralization (right/left), there was no significant difference between th group A and B. No drug side effects were noted in both the groups. CONCLUSION: By usin tamsulosin a higher stone expulsion rates can be achieved in a shorter time. More randomize control trials are required to establish tamsulosin as a standard medical expulsive treatment fc

Zeta potential changing self-nanoemulsifying drug delivery systems: A newfangled approach for enhancing oral bioavailability of poorly soluble drugs.

The mucus is a defensive barrier for different drug-loaded systems. To overcome this obstacle, the crucial factor is the surface charge. Due to mucus negative charge behavior; it was revealed that negatively charged formulations can move across mucus, whereas positively charged nanoformulations could not diffuse via mucus due to interactions. However, cellular intake of negatively charged nanoformulations to the epithelium by endocytosis is less prominent as compared to positively charged carriers. Self-emulsifying drug delivery systems (SEDDS) improve the drug permeability of drugs, especially which have poor oral drug solubility. Moreover, SEDDS have the ability to reduce the degradation of drugs in the GI tract. Currently, drug carrier systems that can shift zeta potential from negative to positive were developed. The benefits of inducing zeta potential changing approach are that negatively charged nanoformulations permeate quickly across the mucus and surface charges reversed to positive at epithelium surface to increase cellular uptake. Among various systems of drug delivery, zeta potential changing SEDDS seem to signify a promising approach as they can promptly diffuse over mucus due to their smaller size and shape distortion ability. Due to such findings, mucus permeation and drug diffusion may improve by the mixture of the zeta potential changing approach and SEDDS.

The structural, biological and dielectric properties of Sr, Mg and Zn doped silicate ceramics.

The current work examines the structural and biological characteristics of doped Zn, Mg, and Sr. Na2O-CaO-Si2O-P2O5 silicate ceramics synthesized by the solid state method. The undoped sample showed amorphous behavior after sintering at the 800 OC while doping of SrO, MgO and ZnO induce crystal growth; and a single phase of Parawollastonite (JCPDS# 00-043-1460) was identified in both doped samples. The strontium doped sample showed the highest value of the dielectric as compared to other three samples. The Sr doped sample had higher dielectric value because the size of Sr2+ is greater than Ca+2 so it will possess the higher polarizing power. Conductivity of Zn and Sr doped samples increased with increase in frequency and Mg doped decrease with increase in frequency. Bioactivity test confirmed that doped samples were more bioactive as compared to undoped samples, and Sr doped sample showed superior bioactivity as compared to other samples.

Chitosan and carboxymethyl cellulose-based 3D multifunctional bioactive hydrogels loaded with nano-curcumin for synergistic diabetic wound repair.

Biopolymer-based thermoresponsive injectable hydrogels with multifunctional tunable characteristics containing anti-oxidative, biocompatibility, anti-infection, tissue regeneration, and/or anti-bacterial are of abundant interest to proficiently stimulate diabetic wound regeneration and are considered as a potential candidate for diversified biomedical application but the development of such hydrogels remains a challenge. In this study, the Chitosan-CMC-g-PF127 injectable hydrogels are developed using solvent casting. The Curcumin (Cur) Chitosan-CMC-g-PF127 injectable hydrogels possess viscoelastic behavior, good swelling properties, and a controlled release profile. The degree of substitution (% DS), thermal stability, morphological behavior, and crystalline characteristics of the developed injectable hydrogels is confirmed using nuclear magnetic resonance (1H NMR), thermogravimetric analysis, scanning electron microscopy (SEM), and x-ray diffraction analysis (XRD), respectively. The controlled release of cur-micelles from the hydrogel is evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC). Furthermore, compared to cur micelles the Cur-laden injectable hydrogel shows a significant increase in half-life (t1/2) up to 5.92 ± 0.7 h, mean residence time (MRT) was 15.75 ± 0.76 h, and area under the first moment curve (AUMC) is 3195.62 ± 547.99 µg/mL*(h)2 which reveals the controlled release behavior. Cytocompatibility analysis of Chitosan-CMC-g-PF127 hydrogels using 3T3-L1 fibroblasts cells and in vivo toxicity by subcutaneous injection followed by histological examination confirmed good biocompatibility of Cur-micelles loaded hydrogels. The histological results revealed the promising tissue regenerative ability and shows enhancement of fibroblasts, keratinocytes, and collagen deposition, which stimulates the epidermal junction. Interestingly, the Chitosan-CMC-g-PF127 injectable hydrogels ladened Cur exhibited a swift wound repair potential by up-surging the cell migration and proliferation at the site of injury and providing a sustained drug delivery platform for hydrophobic moieties.

Hyaluronic acid/alginate-based biomimetic hydrogel membranes for accelerated diabetic wound repair.

The study aims to develop a new multifunctional biopolymer-based hydrogel membrane dressing by adopting a solvent casting method for the controlled release of cefotaxime sodium at the wound site. Sodium alginate enhances collagen production in the skin, which provides tensile strength to healing tissue. Moreover, the significance of extracellular molecules such as hyaluronic acid in the wound the healing cascade renders these biopolymers an essential ingredient for the fabrication of hydrogel membranes via physical crosslinking (hydrogen bonding). These membranes were further investigated in terms of their structure, and surface morphology, as well as cell viability analysis. A membrane with the most suitable characteristics was chosen as a candidate for cefotaxime sodium loading and in vivo analysis. Results show that the 3D porous nature of developed membranes allows optimum water vapor and oxygen transmission (>8.21 mg/mL) to divert excessive wound exudate away from the diabetic wound bed, MTT assay confirmed cell viability at more than 80%. In vivo results confirmed that the CTX-HA-Alg-PVA hydrogel group showed rapid wound healing with accelerated re-epithelization and a decreased inflammatory response. Conclusively, these findings indicate that CTX-HA-Alg-PVA hydrogel membranes exhibit a suitable niche for use as dressing membranes for healing of diabetic wounds.

Folic acid-decorated alginate nanoparticles loaded hydrogel for the oral delivery of diferourylmethane in colorectal cancer.

The disease-related suffering in colorectal cancer remains prevalent despite advancements in the field of drug delivery. Chemotherapy-related side effects and non-specificity remain a challenge in drug delivery. The great majority of hydrophobic drugs cannot be successfully delivered to the colon orally mainly due to poor solubility, low bioavailability, pH differences, and food interactions. Polymeric nanoparticles are potential drug delivery candidates but there are numerous limitations to their usefulness in colon cancer. The nanoparticles are removed from the body rapidly by p-glycoprotein efflux, inactivation, or breakdown by enzymes limiting their efficiency. Furthermore, there is a lack of selectivity in targeting cancer cells; nanoparticles may also target healthy cells, resulting in toxicity and adverse effects. The study aimed to use nanoparticles for specific targeting of the colorectal tumor cells via the oral route of administration without adverse effects. Folic acid (FA), a cancer-targeting ligand possessing a high affinity for folate receptors overexpressed in colorectal cancers was conjugated to sodium alginate- nanoparticles by NH2-linkage. The folic-acid conjugated nanoparticles (FNPs) were delivered to the colon by a pH-sensitive hydrogel synthesized by the free radical polymerization method to provide sustained drug release. The developed system referred to as the "Hydrogel-Nano (HN) drug delivery system," was specifically capable of delivering diferourylmethane to the colon. The HN system was characterized by DLS, FTIR, XRD, TGA, DSC, and SEM. The FNPs size, polydispersity index, and zeta potential were measured. The folic acid-conjugation to nanoparticles' surface was studied by UV-visible spectroscopy using Beer-Lambert's law. In-vitro studies, including sol-gel, porosity, drug loading, entrapment efficiency, etc., revealed promising results. The swelling and release studies showed pH-dependent release of the drug in colonic pH 7.4. Cellular uptake and cytotoxicity studies performed on FR-overexpressed Hela cell lines and FR-negative A-549 cell lines showed facilitated uptake of nanoparticles by folate receptors. A threefold increase in Cmax and prolongation of the mean residence time (MRT) to 14.52 +/- 0.217 h indicated sustained drug release by the HN system. The findings of the study can provide a sufficient ground that the synergistic approach of the HN system can deliver hydrophobic drugs to colorectal cancer cells via the oral route, but further in-vivo animal cancer model studies are required.