Assessment of pheniramine in alternative biological matrices by liquid chromatography tandem mass spectrometry.

Pheniramine is an over-the-counter antihistamine drug. Its accessibility and low cost made it more popular among drug abusers in Pakistan. In this study, pheniramine was quantified in both conventional and alternative specimens of twenty chronic drug abusers, aged 16-50 years, who were positive for pheniramine in comprehensive toxicological screening for drugs by gas chromatography with mass spectral detection in positive electron impact mode. Pheniramine was extracted from biological specimens using solid phase extraction and liquid chromatography tandem mass spectrometry was employed for quantification. Chromatographic separation was carried out on a Poroshell120EC-18 (2.1 mm × 50 mm × 2.7 µm) column using water-acetonitrile in formic acid (0.1%) mobile phase in gradient elution mode with 500 µL/min flow rate. Positive electrospray ionization mode and multi-reaction monitoring with ion transitions m/z 241.3 → 195.8 and 167.1 for pheniramine and m/z m/z 247.6 → 173.1 for pheniramine-d6 were employed. The quantification method showed good linear ranges of 2-1000 ng/mL in blood, urine, and oral fluid; 2-1000 ng/mg in hair and 5-1000 ng/mg in nail with ≥ 0.985% coefficient of linearity. The retention time of pheniramine was 3.0 ± 0.1 min. The detection and lower quantification limits were 1 ng/mL and 2 ng/mL for blood, urine, oral fluid and hair whereas 2.5 ng/mg and 5 ng/mg for nail, respectively. Mean extraction recovery and ionization suppression ranged 86.3-95.1% and -4.6 to -14.4% in the studied matrices. Intra-day and inter-day precision were 4.1-9.3% and 2.8-11.2%, respectively. Pheniramine levels in specimens of drug abusers were 23-480 ng/mL in blood, 72-735 ng/mL in urine, 25-379 ng/mL in oral fluid, 10-170 ng/mg in hair and 8-86 ng/mg in nail specimens. Alternative specimens are of utmost significance in clinical and medico-legal cases. In this study, authors compared matrix-matched calibration curves to blood calibration curve and obtained results within ± 10%; thereby justifying the use of blood calibration curve for urine, oral fluid, hair, and nail specimens.

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol.

PURPOSE: The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release. METHODS: Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels. RESULTS: The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively). CONCLUSIONS: As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT.

Green synthesis of quince/pectin cross-linked superporous hydrogel sponges for pH-regulated sustained domperidone delivery.

The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of domperidone. The designed hydrogel sponges were evaluated for a sol-gel fraction (%), swelling studies and kinetics, drug loading (%), electrolyte-responsive character, scanning electron microscopy (SEM), thermal analysis, drug-excipient compatibility studies (FTIR), X-ray diffraction (XRD) analysis, mechanical testing, in-vitro drug release studies, and acute oral toxicity studies. The drug loading (%) ranged from 67 to 85%. Hydrogel sponges displayed pH-responsive swelling potential, with optimum swelling in a phosphate buffer (pH 7.4) and insignificant swelling in an acidic buffer of pH 1.2. The prepared hydrogel sponges displayed second-order swelling dynamics. The FTIR data revealed the successful fabrication of the hydrogel sponges with the primary drug peaks remaining unchanged, demonstrating excipients-drug compatibility. SEM confirmed the rough, porous surface of hydrogel sponges with numerous cracks. XRD measurements revealed the transformation of the crystalline nature of domperidone into an amorphous one within the developed hydrogel sponges. Dissolution studies revealed little domperidone release in an acidic environment. However, hydrogel sponges exhibited release up to 10 h in phosphate buffer.The sponge's non-toxic or biocompatible character was confirmed through toxicological studies. Thus, the finding indicates that quince/pectin cross-linked hydrogel sponges are durable enough to deliver the domperidone to the gut for a longer time.

Flexible Topical Hydrogel Patch Loaded with Antimicrobial Drug for Accelerated Wound Healing.

A hydrogel topical patch of neomycin was developed by using sodium alginate (SA) and hydroxyethylcellulose (HEC) as polymers. Free radical polymerization in an aqueous medium was initiated by using acrylic acid (AA) and N,N'-methylenebisacrylamide (MBA). Prepared hydrogels were characterized for pH sensitivity and sol-gel analysis. In addition, the effect of reactant contents on the developed formulation was evaluated by swelling behavior. SEM assay showed the rough structure of the hydrogel-based polymeric matrix, which directly enhances the ability to uptake fluid. FTIR spectra revealed the formation of a new polymeric network between reactant contents. TGA and DSC verified that fabricated polymeric patches were more thermodynamically stable than pure components. Gel fractions increased with increases in polymer, monomer, and cross-linker contents. The swelling study showed the pH-dependent swelling behavior of patches at pH 5.5, 6.5, and 7.4. The release pattern of the drug followed zero-order kinetics, with diffusion-controlled drug release patterns according to the Korsmeyer-Peppas (KP) model. Ex vivo studies across excised rabbit skin verified the drug retention in the skin layers. The hydrogel patch effectively healed the wounds produced on the rabbit skin, whereas the formulation showed no sign of irritation on intact skin. Therefore, neomycin hydrogel patches can be a potential candidate for controlled delivery for efficient wound healing.

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

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

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation.

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol-gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63-75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen-Crowell's kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.

Assessment of formulation variables of poor water soluble diacerein for its improved loading and anti-inflammatory activity.

Dissolving microneedles have become a popular method for percutaneous administrationof drugs. However, loading poorly soluble drugs into water-based dissolving microneedles remains a challenge. In view of this, we aimed to improve Diacerein (DCN) solubility formulating dissolving microneedles. DCN microsuspension was created by high-speed homogenization with organic solvents or wet milling with Tween 80 as a stabilizer (LD1). They were analyzed for particle size and saturation solubility. Subsequently, the organic solvent-based microneedles were prepared under vacuum, whereas LD1 was mixed with HPMC (8% w/w) and PVP (30% w/w) matrix to concentrate the drug in acral fraction through centrifugation. DCN microsuspension in DMSO had the highest drug solubility with an average particle size of 6 µm, whereas LD1 had a particle size of 3.28 µm showing improved solubility. TD-3 had the highest drug loading and the least amount of drug migration into the blank baseplate. Within 5 min, these microneedles dissolved completely in an agarose-gel block. LD1 was likewise put in the baseplate to generate TD3-B. Within 24 h, 74.39% of the medication was released from TD3-B, with only a small amount remaining in the baseplate. TLC examination indicated the conversion of DCN to Rhein in the skin, whereas DSC and TGA studies revealed amorphous features. DCN microneedles showed no sign of skin irritancy but showed anti-inflammatory response on carrageenan-induced paw edema model. Microneedles remained stable during accelerated stability testing. Wet milling in the presence of a stabilizer can be an effective approach for enhancing DCN solubility for improved drug loading in dissolving microneedles. Improvement in solubility of Diacerein for subsequent loading in Dissolving Microneedle for percutaneous delivery.

Development of a Novel Self-Dissolving Microneedle-Assisted Percutaneous Delivery System of Diacerein through Solid Dispersion Gel: Solubility Enhancement, Proof of Anti-inflammatory Activity and Safety.

BACKGROUND: Diacerein, an osteoarthiritis drug, experiences slow topical permeation due to limited solubility. Additionally, it shows a laxative effect due to acid/base hydrolysis of the drug in the colon. OBJECTIVE: Diacerein solubility was improved to increase percutaneous drug delivery. METHODS: To improve saturation solubility of the drug, Diacerein was pre-treated with Polysorbate 80 aqueous solution (1% v/v) to obtain lyophilized powder after wet milling or formulated as solid dispersion using PEG 4000 by fusion method. The lyophilized Diacerein in hydroxypropyl methylcellulose (HPMC 8% w/w) and polyvinyl pyrrolidone (PVP 30% w/w) matrix, with PEG 400 as co-solvent, provided an optimized array. The solid dispersion was loaded in the CMC based gel for subsequent administration on dissolving microneedle-treated skin. RESULTS: The addition of PEG 400 increased Diacerein loading in microneedles to 390.35±4.28 µg per array. The lyophilized drug displayed amorphous characteristics in the dissolving microneedles as per XRD analysis. SEM photographs showed uniformity in the surface topology of microneedles. The needles showed rapid polymer dissolution within 5 minutes, whereas methylene-blue distribution confirmed the formation of microcavities in excised rat skin. The drug-loaded arrays showed better permeation (74.39%) and skin deposition (15.75%) after 24 hours, however, ⁓12% of Diacerein remained in the baseplate. This led to the tailoring of CMC-based gel (3% w/v) containing 0.4% solid dispersion of Diacerein. When compared to untreated skin, the gel improved permeation rate by 2.43 folds through aqueous microchannels generated by dissolving microneedle pre-treatment and allowed 98% drug permeation. The quasi-Fickian diffusion mechanism was found to drive ex vivo release kinetics, with a shorter lag time (0.88 h) and higher flux (26.65 µg/sq.cm.h). Microneedle-assisted Diacerein gel showed a positive anti-inflammatory effect in the paw edema model and reduced diarrheal episodes in comparison to the marketed oral formulation. The gel showed desired characteristics at 5°C±2°C when tested under accelerated stability conditions. CONCLUSION: The present study reports for the first time the verification of efficacy and safety to advocate the suitability of Diacerein for percutaneous delivery through dissolving microneedle-treated skin.

Caftaric Acid Ameliorates Oxidative Stress, Inflammation, and Bladder Overactivity in Rats Having Interstitial Cystitis: An In Silico Study.

Interstitial cystitis (IC) is the principal unwanted effect associated with the use of cyclophosphamide (CYP). It results in increased oxidative stress, overexpression of proinflammatory cytokines, and bladder overactivity. Patients receiving CYP treatment had severely depreciated quality of life, as the treatment available is not safe and effective. The goal of this study was to assess the protective effect of caftaric acid in CYP-induced IC. IC was induced in female Sprague Dawley by injecting CYP (150 mg/kg, i.p.). In the present study, oral administration of caftaric acid (20, 40, and 60 mg/kg) significantly decreased inflammation. Caftaric acid significantly increased SOD (93%), CAT (92%), and GSH (90%) while decreased iNOS (97%), IL-6 (90%), TGF 1-ß (83%), and TNF-α (96%) compared to the diseased. DPPH assay showed the antioxidant capacity comparable to ascorbic acid. Molecular docking of caftaric acid with selected protein targets further confirmed its antioxidant and anti-inflammatory activities. The cyclophosphamide-induced bladder overactivity had been decreased possibly through the inhibition of M3 receptors, ATP-sensitive potassium channels, calcium channels, and COX enzyme by caftaric acid. Therefore, our findings demonstrate that caftaric acid has a considerable protective role against CYP-induced IC by decreasing the oxidative stress, inflammation, and bladder smooth muscle hyperexcitability. Thus, caftaric acid signifies a likely adjuvant agent in CYP-based chemotherapy treatments.

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study.

OBJECTIVE: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. METHODS: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. RESULTS: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. CONCLUSION: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

Anti-Inflammatory, analgesic and anti-pyretic activity of Fagonia bruguieri DC in rats.

Traditional medicine has employed the plant Fagonia bruguieri DC. to alleviate inflammation, fever and pain. The goal of this study was to test the anti-inflammatory, analgesic and antipyretic properties of the methanol extract of whole plant of Fagonia bruguieri (F. bruguieri). The writhing test and Eddy's hot plate test were used to assess the analgesic potential of F. bruguieri at three different doses. Carrageenan-induced rat paw edema was applied to investigate anti-inflammatory activity, whereas antipyretic activity was estimated in Brewer's yeast induced pyrexia model. Flavonoids, alkaloids, saponins, tannins and glycosides were found in F. bruguieri's phytochemical analysis. F. bruguieri at 750 mg/kg reduced writhing count by 62.23 percent, while F. bruguieri enhanced latency in Eddy's hot plate test. In carrageenan-induced edema, F. bruguieri at 750 mg/kg exhibited considerable anti-inflammatory effect (41.11 percent) after 2 nd, 3 rd and 4 th hours of therapy. F. bruguieri was also found to show antipyretic properties. The anti-inflammatory, analgesic and antipyretic properties of F. bruguieri were confirmed in this study, which might be attributable to the presence of several phyto-constituents.

Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug's Solubility Improvement.

Poor solubility is a global issue of copious pharmaceutical industries as large number of drugs in development stage as well as already marketed products are poorly soluble which results in low dissolution and ultimately dosage increase. Current study is aimed at developing a polyvinylpyrrolidone- (PVP-K30-) based nanogel delivery system for solubility enhancement of poorly soluble drug olanzapine (OLP), as solubilization enhancement is the most noteworthy application of nanosystems. Crosslinking polymerization with subsequent condensation technique was used for the synthesis of nanogels, a highly responsive polymeric networks in drug's solubility. Developed nanogels were characterized by percent entrapment efficiency, sol-gel, percent swelling, percent drug loaded content (%DLC), percent porosity, stability, solubility, in vitro dissolution studies, FTIR, XRD, and SEM analysis. Furthermore, cytotoxicity study was conducted on rabbits to check the biocompatibility of the system. Particle size of nanogels was found with 178.99 ± 15.32 nm, and in vitro dissolution study exhibited that drug release properties were considerably enhanced as compared to the marketed formulation OLANZIA. The solubility studies indicated that solubility of OLP was noticeably improved up to 36.7-fold in phosphate buffer of pH 6.8. In vivo cytotoxicity study indicated that prepared PVP-K30-based formulation was biocompatible. On the basis of results obtained, the developed PVP-K30-co-poly (AMPS) nanogel delivery system is expected to be safe, effective, and cost-effective for solubility improvement of poorly soluble drugs.

Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers.

The aim of the proposed study is to develop a mucoadhesive buccal delivery system for the sustained delivery of metformin (MET) and sitagliptin (SIT) against diabetes mellitus (DM) with improved bioavailability. Polymeric blend of Carbopol® 940 (CP), agarose (AG) or polyvinylpyrrolidone K30 (PVP) as mucoadhesive agents in formulations (R1-R15) were compressed via the direct compression technique. Tablets were characterized for solid state studies, physicochemical and in vivo mucoadhesion studies in healthy volunteers. Outcomes did not reveal any unusual peak or interaction between the drugs and polymers in the physical mixture through Fourier Transform Infrared Spectroscopy (FTIR) and DSC analysis. The mucoadhesive blend of CP and PVP was superior compared to other blends. The formulation R4 revealed exorbitant loading of drugs with complete drug release for 6 h with ex vivo mucoadhesive strength and time of 26.99 g and 8.1 h, respectively. It was further scrutinized to evaluate it as an optimized formulation where it was found to be stable for up to 6 months. The formulation R4 depicted Korsmeyer-Peppas model and first-order mode of release correspondingly for SIT and MET. Moreover, it showed hemocompatibility, biocompatibility and stability with non-significant changes in the dissolution profile. Overall, the CP blend with PVP was found appropriate to yield the desired release coupled with the optimized mucoadhesive properties of the buccal tablets, ensuring sufficient pharmaceutical stability.

pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation.

The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin's lymphoma. The Hydrogels were prepared using a polymeric blend of agarose, Pluronic acid, glutaraldehyde, and methacrylic acid. The prepared hydrogels were characterized for drug loading (%), swelling pattern, release behavior, the ingredient's compatibility, structural evaluation, thermal integrity, and toxicity evaluation in rabbits. The new polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 58.65-75.32%. The developed hydrogels showed significant differences in swelling dynamics and drug release behavior in simulated intestinal fluid (SIF) when compared with simulated gastric fluid (SGF). The drug release was persistent and performed in a controlled manner for up to 24 h. A toxicity study was conducted on white albino rabbits. The developed hydrogels did not show any signs of ocular, skin, or oral toxicity; therefore, these hydrogels can be regarded as safe and potential carriers for controlled drug delivery in biomedical applications.

Feasibility of Enhancing Skin Permeability of Acyclovir through Sterile Topical Lyophilized Wafer on Self-Dissolving Microneedle-Treated Skin.

Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10-26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer-drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7-11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours' study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.

Development and Evaluation of pH-Responsive Pluronic F 127 Co-Poly- (Acrylic Acid) Biodegradable Nanogels for Topical Delivery of Terbinafine HCL.

Research aimed to develop and evaluate biodegradable, pH-responsive chemically cross-linked Pluronic F127 co-poly- (acrylic acid) nanogels for dermal delivery of Terbinafine HCL (TBH) to increase its permeability and as a new approach to treat skin fungal infections. TBH-loaded nanogels were successfully synthesized from acrylic acid (AA) and Pluronic F127 by free-radical copolymerization technique using N,N'-methylene bisacrylamide (MBA) as crosslinker and ammonium persulphate (APS) as initiator. Prepared nanogels exhibited 93.51% drug entrapment efficiency (DEE), 45 nm particle size, pH-dependent swelling and release behavior. Nanogels were characterized using different physicochemical techniques. The ex-vivo skin retention studies through rat skin showed about 42.34% drug retention from nanogels while 1% Lamisil cream (marketed product) showed about 26.56% drug retention. Moreover, skin irritation studies showed that nanogels were not irritating. Nanogels showed improved in-vitro antifungal activity against Candida albicans compared to commercial product. In-vivo studies on rats infected with Candida albicans confirmed superiority of nanogels over 1% Lamisil for eradication of fungal infection. This confirms that TBH loaded in Pluronic F127 co-poly-(acrylic acid) nanogels provided greater targetibility and cure rates of poorly soluble TBH in animal model and hence nanogels could be a potential carrier for effective topical delivery of TBH for skin fungal infection treatment.

Corrigendum: Chitosan/Xanthan Gum based hydrogels as potential carrier for an antiviral drug: Fabrication, characterization, and safety evaluation.

[This corrects the article DOI: 10.3389/fchem.2020.00050.].

Designing of SiO2 mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: Ex vivo evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression.

The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol-gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect.

Preparation of smart PVP/HPMC based IPN hydrogel, its characterization and toxicity evaluation.

In this study, the interpenetrating polymeric network (IPN) were fabricated via free radical polymerization using polymers hydroxypropyl methylcellulose (HPMC), Polyvinylpyrrolidone (PVP) and monomer Methacrylic acid (MAA) and also investigated their influence by changing their concentrations. The developed polymeric network is crosslinked via N' N' -methylene bis-acrylamide (MBA). Different characterizations have been performed to analyze fabricated interpenetrating polymeric network structure i.e., Scanning Electron Microscopy (SEM), X-ray Powder Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Letrozole (LTZ) was loaded as a model drug in the developed system. Swelling dynamics as well as drug release behavior were thoroughly examined. FTIR studies corroborated the formation of interpenetrating polymeric network. SEM uncovered porous structure while TGA depicted enhanced thermal stability of polymeric network. PXRD depicted amorphous dispersion of LTZ. Swelling dynamics as well as LTZ release behavior from developed interpenetrating polymeric network hydrogels were dependent upon pH of the medium and concentration of pure reactants employed. Higuchi model was best fit to regression coefficient which indicated diffusion controlled mechanism of drug release. Acute oral toxicity study depicted no mortality or any signs relating to acute toxicity throughout the whole observed period. Hence, the designed interpenetrating polymeric network might turn out to be a safe and a potential carrier system for the delivery of LTZ in the treatment of breast cancer (BC).