Fabrication, optimisation and evaluation of cisplatin-loaded nanostructured carriers for improved urothelium permeability for intravesical administration.

AIM: To design microemulsions as carriers to improve cisplatin permeation capability for intravesical administration. METHOD: The response surface methodology with factorial design was used to investigate and optimise the influence of the compositions e.g. capryol 90 and 5-pentanediol/transcutol mixture on the permeation accumulation amount and tissue deposition amount of cisplatin-loaded microemulsions. The in vitro permeation study and in vivo intravesical test were conducted to prove the effect of microemulsions. RESULTS: The droplet size and the viscosity of all drug-loaded formulations ranged 235.8-309.3 nm and 550.8-861.7 cps, respectively. The permeation accumulation amounts significantly increased about 26-fold, by used microemulsion as carriers. In vivo study, the cisplatin deposition amount in bladder tissue significantly increased 4.1-fold (p < 0.05) and the penetration depth increased from 60 µm up 120 µm. The nanocarrier showed considerable thermodynamic stability. CONCLUSION: The designed nanocarrier was considered to be a promising delivery system for cisplatin intravesical administration.

Erratum - A Novel Model for Studying Voltage-Gated Ion Channel Gene Expression during Reversible Ischemic Stroke.

[This corrects the article DOI: 10.7150/ijms.27442.].

A Novel Model for Studying Voltage-Gated Ion Channel Gene Expression during Reversible Ischemic Stroke.

The dysfunction of voltage-gated ion channels contributes to the pathology of ischemic stroke. In this study, we developed rat models of transient ischemic attack (TIA) and reversible ischemic neurological deficit (RIND) that was induced via the injection of artificial embolic particles during full consciousness, that allow us to monitor the neurologic deficit and positron emission tomography (PET) scans in real-time. We then evaluated the infarction volume of brain tissue was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and gene expressions were evaluated by quantitative real-time PCR (qPCR). We found that rats with TIA or RIND exhibited neurological deficits as determined by negative TTC and PET findings. However, the expression of voltage-gated sodium channels in the hippocampus was significantly up-regulated in the qPCR array study. Furthermore, an altered expression of sodium channel ß-subunits and potassium channels, were observed in RIND compared to TIA groups. In conclusion, to our knowledge, this is the first report of the successful evaluation of voltage-gated ion channel gene expression in TIA and RIND animal models. This model will aid future studies in investigating pathophysiological mechanisms, and in developing new therapeutic compounds for the treatment of TIA and RIND.

A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment.

Photodynamic therapy (PDT) is a widely used technique for epithelial skin cancer treatment. 5-aminolevulinic acid (5-ALA) is a drug currently used for PDT and is a hydrophilic molecule at its physiological pH, and this limits its capacity to cross the stratum corneum of skin. Since skin penetration is a key factor in the efficacy of topical 5-ALA-mediated PDT, numerous strategies have been proposed to improve skin penetration. Yet this problem is still ongoing. The results of a previous study showed a low rate of 5-ALA encapsulated in liposomes (5.7%) that were 400 nm in size. In the present study, we used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as vehicles and tested their delivery efficacy of 5-ALA-medicated PDT both in vitro and in vivo. Our data shows that 5-ALA encapsulated in 0.1 or 0.5% DPPC liposomes (5-ALA/DPPC) had a better encapsulated rate (15~16%) and were smaller in size (84~89 nm). We found the 5-ALA/DPPC formulation reduced cell viability, mitochondria membrane potential, and enhanced intracellular ROS accumulation as compared to 5-ALA alone in melanoma cells. Furthermore, the 5-ALA/DPPC formulation also had better skin penetration ability as compared to the 5-ALA in our ex vivo data by assaying 5-ALA converted into protoporphyrin IX (PpIX) in the skin of the mice that were experimented on. In melanoma xenograft models, 5-ALA/DPPC enhanced PpIX accumulation only in tumor tissue but not normal skin. In conclusion, we found DPPC liposomes to be good carriers for 5-ALA delivery and believe that they may prove useful in 5-ALA-mediated PDT in the future.

Anti-oxidant activity and attenuation of bladder hyperactivity by the flavonoid compound kaempferol.

OBJECTIVES: To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. METHODS: The anti-oxidative activity of kaempferol was examined in lipopolysaccharide-treated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. RESULTS: Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. CONCLUSION: Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury.

Formulation optimization of arecoline patches.

The response surface methodology (RSM) including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS), Eudragit RL 100 (ERL) and polyvinylpyrrolidone K30 (PVP), plasticizers (PEG 400), and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline.

Formulation and In Vitro Assessment of Polymeric pH-Responsive Nanogels of Chitosan for Sustained Delivery of Madecassoside.

Madecassoside, a triterpenoid saponin compound mainly isolated from the gotu kola herb (Centella asiatica), shows an extensive range of biological activities, including antiapoptotic, antioxidant, anti-inflammatory, moisturizing, neuroprotective, and wound healing effects. It has been highly used in the management of eczema, skin wounds, and other diseases. Due to poor oral bioavailability, membrane permeability, and intestinal absorption, the clinical application of the madecassoside is limited. Hence, a drug carrier system is needed that not only sustains the release of the madecassoside but also overcomes the drawbacks associated with its administration. Therefore, the authors prepared novel pH-responsive chitosan-based nanogels for the sustained release of madecassoside. Free radical polymerization technique was used for cross-linking of polymer chitosan and monomer methacrylic acid in the presence of cross-linker N',N'-methylene bis(acrylamide). The decrease in polymer crystallinity after polymerization and development of nanogels was demonstrated by XRD and FTIR analysis. The effects of nanogel contents on polymer volume, sol-gel analysis, swelling, drug loading, and release were investigated. Results indicated that high swelling and maximum release of the drug occurred at pH 7.4 compared to pH 1.2 and 4.6, indicating the excellent pH-sensitive nature of the engineered nanogels. High swelling and drug release were perceived with the integration of a high quantity of chitosan, while a decline was observed with the high integration of N',N'-methylene bis(acrylamide) and methacrylic acid contents. The same effects of nanogel contents were shown for drug loading too. Sol fraction was reduced, while gel fraction was enhanced by increasing the chitosan load, N',N'-methylene bis(acrylamide), and methacrylic acid. The Korsmeyer-Peppas model of kinetics was trailed by all nanogel formulations with non-Fickian diffusion. The results demonstrated that prepared nanogels can be employed for sustained release of the madecassoside.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

BACKGROUND: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. AIM: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. OBJECTIVE: The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. METHODS: Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. RESULTS: FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. CONCLUSION: The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

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

AIM AND OBJECTIVE: 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. BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: The results indicated that prepared PVA/AA hydrogels can be used as an alternative approach for the controlled delivery of diclofenac sodium.

Isotretinoin oil-based capsule formulation optimization.

The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1), hydrogenated coconut oil (X2), and soybean oil (X3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3) showed more potential influence than that of the main factors (X1, X2, and X3). An optimal predicted formulation with Y(10 min), Y(30 min), Y(60 min), and Y(90 min) release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile.

The transport effect of submicron emulsions on 5-flurouracil topical application.

Water-in-oil submicron emulsions were used as carrier for the topical delivery of 5-fluorouracil (5FU). The effect of components such as level and hydrophilic-lipophilic balance (HLB) value of surfactant, type of cosurfactant, and drug concentration on the delivery capability of drug in the receptor fluid and in the various skin layers (stratum corneum, epidermis and dermis) were evaluated. The result showed the submicron emulsion could increase the transdermal and deposition of 5FU compared with the aqueous control. Submicron emulsion with surfactant at HLB of 6.0 had higher deposition amount of drug in epidermis layer. The deposition amount of drug in the skin layers increased with increased amounts of surfactant and drug loading of submicron emulsion. However, the 0.2% 5FU-load submicron emulsion showed a comparable deposition effect in various skin layers with the commercial product (5%, Efudix®), which indicated that the submicron emulsions could be a promising drug vehicle for topical application.

Improvement in Skin Penetration Capacity of Linalool by Using Microemulsion as a Delivery Carrier: Formulation Optimization and In Vitro Evaluation.

Linalool is an aromatic oil with analgesic, anti-inflammatory and anti-UVB-induced skin damage effects. The aim of this study was to develop a linalool-loaded microemulsion formulation for topical application. In order to quickly obtain an optimal drug-loaded formulation, statistical tools of the response surface methodology and a mixed experimental design with four independent variables of oil (X1), mixed surfactant (X2), cosurfactant (X3) and water (X4) were used to design a series of model formulations in order to analyze the effect of the composition on the characteristics and permeation capacity of linalool-loaded microemulsion formulations and to obtain an appropriate drug-loaded formulation. The results showed that the droplet size, viscosity and penetration capacity of linalool-loaded formulations were significantly affected by formulation component proportions. The skin deposition amount of the drug and flux of such formulations expressively increased about 6.1-fold and 6.5-fold, respectively, when compared to the control group (5% linalool dissolved in ethanol). After 3 months of storage, the physicochemical characteristics and drug level did not show a significant change. The linalool formulation-treated rat skin showed non-significant irritation compared to skin treatments in the distilled-water-treated group. The results showed that specific microemulsion applications might be considered as potential drug delivery carriers for essential oil topical application.

Fabrication and In vitro Evaluation of Carbopol/Polyvinyl Alcohol-based pH-sensitive Hydrogels for Controlled Drug Delivery.

BACKGROUND: Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium. AIMS: This study aimed to fabricate and evaluate carbopol/polyvinyl alcohol-based pH-sensitive hydrogels for controlled drug delivery. OBJECTIVE: pH-sensitive carbopol/polyvinyl alcohol graft-poly(acrylic acid) hydrogels (Cp/PVA-g-PAa hydrogels) were developed for the controlled delivery of diclofenac sodium. METHODS: The combination of carbopol/polyvinyl alcohol, acrylic acid, and ethylene glycol dimethacrylate was used as polymer, monomer, and cross-linker, respectively. The effects of the formulation's composition on porosity, swelling index, and release pattern of diclofenac sodium from the developed hydrogels were investigated. RESULTS: An increase in porosity and swelling was observed with the increasing amounts of carbopol and acrylic acid, whereas polyvinyl alcohol showed the opposite effect. Due to the formation of a highly viscous system, the drug release decreased with the increasing concentrations of carbopol and polyvinyl alcohol while increased with increasing acrylic acid concentration. The pH-responsive properties of the fabricated hydrogels were demonstrated by dynamic swelling and drug release studies at three different pH values. Higher dynamic swelling and diclofenac sodium (model drug) release were found at high pH values compared to low pH values, i.e., pH 7.4 > 4.6 > 1.2, respectively. Cytotoxicity studies reported no toxic effect of the prepared hydrogels, thus indicating that the prepared hydrogels are safe to be used on clinical basis. CONCLUSION: The prepared carbopol/polyvinyl alcohol crosslinked hydrogel can be used as a promising carrier for the controlled release of drugs.

Xanthan-Gum/Pluronic-F-127-Based-Drug-Loaded Polymeric Hydrogels Synthesized by Free Radical Polymerization Technique for Management of Attention-Deficit/Hyperactivity Disorder.

Smart and intelligent xanthan gum/pluronic F-127 hydrogels were fabricated for the controlled delivery of atomoxetine HCl. Different parameters such as DSC, TGA, FTIR, XRD, SEM, drug loading, porosity, swelling index, drug release, and kinetics modeling were appraised for the prepared matrices of hydrogels. FTIR confirmed the successful synthesis of the hydrogel, while TGA and DSC analysis indicated that the thermal stability of the reagents was improved after the polymerization technique. SEM revealed the hard surface of the hydrogel, while XRD indicated a reduction in crystallinity of the reagents. High gel fraction was achieved with high incorporated contents of the polymers and the monomer. An increase in porosity, drug loading, swelling, and drug release was observed with the increase in the concentrations of xanthan gum and acrylic acid, whereas Pluronic F-127 showed the opposite effect. A negligible swelling index was shown at pH 1.2 and 4.6 while greater swelling was observed at pH 7.4, indicating a pH-responsive nature of the designed hydrogels. Furthermore, a higher drug release was found at pH 7.4 compared to pH 1.2 and 4.6, respectively. The first kinetics order was followed by the prepared hydrogel formulations. Thus, it is signified from the discussion that smart xanthan gum/pluronic F-127 hydrogels have the potential to control the release of the atomoxetine HCl in the colon for an extended period of time.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

The effect of submicron emulsion systems on transdermal delivery of kaempferol.

In this study, submicron emulsions have been employed as a carrier for the topical application of kaempferol. The effect of components of submicron emulsions on the physicochemical properties and permeation capability of drug were evaluated. In case of drug-loaded submicron emulsions, the cumulative amount over 12 h (Q(12 h)), lag time and deposition in skin amount ranged from 13.0±3.4 to 236.1±21.2 µg/cm(2), 1.7 to 5.3 h, and 1.10 to 7.76 µg/cm(2), respectively, which indicated that the permeation parameters of kaempferol were markedly influenced by the component ratio. Kaempferol dispensed in isopropyl myristate was used as the control. The Q(12 h), lag time and deposition amount in skin were 4.2±1.8 µg/cm(2), 6.0 h and 2.25±0.60 µg/cm(2), respectively. The data showed that used appropriate submicron emulsions as vehicle could significantly increase the Q(12 h) and deposition amount in skin and shorten the lag time, demonstrating that submicron emulsions have a potent enhancement effect for kaempferol transdermal delivery.

Formulation, Characterization, and In Vitro Drug Release Study of ß-Cyclodextrin-Based Smart Hydrogels.

In this study, novel pH-responsive polymeric ß-cyclodextrin-graft-poly(acrylic acid/itaconic acid) hydrogels were fabricated by the free radical polymerization technique. Various concentrations of ß-cyclodextrin, acrylic acid, and itaconic acid were crosslinked by ethylene glycol dimethacrylate in the presence of ammonium persulfate. The crosslinked hydrogels were used for the controlled delivery of theophylline. Loading of theophylline was conducted by the absorption and diffusion method. The fabricated network of hydrogel was evaluated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The crosslinking among hydrogel contents and drug loading by the fabricated hydrogel were confirmed by FTIR analysis, while TGA indicated a high thermal stability of the prepared hydrogel as compared to pure ß-cyclodextrin and itaconic acid. The high thermal stability of the developed hydrogel indicated an increase in the thermal stability of ß-cyclodextrin and itaconic acid after crosslinking. Similarly, a decrease in crystallinity of ß-cyclodextrin and itaconic acid was observed after crosslinking, as evaluated by XRD analysis. SEM revealed an irregular and hard surface of the prepared hydrogel, which may be correlated with strong crosslinking among hydrogel contents. Crosslinked insoluble and uncrosslinked soluble fractions of hydrogel were evaluated by sol-gel analysis. An increase in gel fraction was seen with the increase in compositions of hydrogel contents, while a decrease in sol fraction was observed. Dynamic swelling and dissolution studies were performed in three various buffer solutions of pH 1.2, 4.6, and 7.4, respectively. Maximum swelling and drug release were observed at higher pH values as compared to the lower pH value due to the deprotonation and protonation of functional groups of the hydrogel contents; thus, the pH-sensitive nature of the fabricated hydrogel was demonstrated. Likewise, water penetration capability and polymer volume were evaluated by porosity and polymer volume studies. Increased incorporation of ß-cyclodextrin, acrylic acid, and itaconic acid led to an increase in swelling, drug release, drug loading, and porosity of the fabricated hydrogel, whereas a decrease was detected with the increasing concentration of ethylene glycol dimethacrylate. Conclusively, the prepared hydrogel could be employed as a suitable and promising carrier for the controlled release of theophylline.

Designing of pH-Sensitive Hydrogels for Colon Targeted Drug Delivery; Characterization and In Vitro Evaluation.

In the current research work, pH-sensitive hydrogels were prepared via a free radical polymerization technique for the targeted delivery of 5-aminosalicylic acid to the colon. Various proportions of chitosan, ß-Cyclodextrin, and acrylic acid were cross-linked by ethylene glycol dimethacrylate. Ammonium persulfate was employed as an initiator. The development of a new polymeric network and the successful encapsulation of the drug were confirmed by Fourier transform infrared spectroscopy. Thermogravimetric analysis indicated high thermal stability of the hydrogel compared to pure chitosan and ß-Cyclodextrin. A rough and hard surface was revealed by scanning electron microscopy. Similarly, the crystallinity of the chitosan, ß-Cyclodextrin, and fabricated hydrogel was evaluated using powder X-ray diffraction. The swelling and drug release studies were performed in both acidic and basic medium (pH 1.2 and 7.4, respectively) at 37 °C. High swelling and drug release was observed at pH 7.4 as compared to pH 1.2. The increased incorporation of chitosan, ß-Cyclodextrin, and acrylic acid led to an increase in porosity, swelling, loading, drug release, and gel fraction of the hydrogel, whereas a decrease in sol fraction was observed. Thus, we can conclude from the results that a developed pH-sensitive network of hydrogel could be employed as a promising carrier for targeted drug delivery systems.

Preparation of pH-Responsive Hydrogels Based on Chondroitin Sulfate/Alginate for Oral Drug Delivery.

This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N',N'-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine.

Association of COVID-19 vaccination with herpes zoster: a systematic review and meta-analysis.

BACKGROUND: Following COVID-19 vaccination, several herpes zoster cases have been reported, making it critical to explore the association between herpes zoster and COVID-19 vaccination. This is especially true in the context of increasing the number of participants enrolled to receive COVID-19 vaccination. RESEARCH DESIGN AND METHODS: Three databases, including the Cochrane Library, PubMed, and EMBASE, were searched for relevant studies before 25 December 2021 according to preliminarily determined inclusion and exclusion criteria without any language limitations. Four cohort studies were included in this systematic review and meta-analysis. RESULTS: Compared with the placebo group, there was no evidence that the COVID-19 vaccination group was associated with increased incidence of herpes zoster (Risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.91 to 1.24). There is no evidence that the COVID-19 vaccination from Moderna is associated with the incidence of herpes zoster compared with vaccination from Pfizer (RR: 0.20; 95% CI: 0.01 to 2.99). CONCLUSIONS: To date, there is no evidence of an association between covid-19 vaccination and herpes zoster.