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.

Synthesis of novel combinatorial drug delivery system (nCDDS) for co-delivery of 5-fluorouracil and leucovorin calcium for colon targeting and controlled drug release.

OBJECTIVE: Purpose of the current study was to improve the oral effectiveness of 5-fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and leucovorin calcium (LC) for colon targeting. SIGNIFICANCE: On the basis of results obtained, novel controlled, combinatorial drug delivery system could be an effective strategy for the colon targeting of 5-FU and LC. METHODS: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, first synthesis of 5-FU/LC calcium loaded nanogels and second, pre-synthesized 5-FU and LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDDS gels were characterized for network structure, thermal stability, and surface morphology. Swelling and in vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. RESULTS: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in vitro and in vivo characterizations. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and nontoxic characteristics of developed formulation. CONCLUSION: Conclusively, it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.

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).

Antiviral activity of green silver nanoparticles produced using aqueous buds extract of Syzygium aromaticum.

In the present study, we synthesized silver (Ag) nanoparticles using aqueous extracts of clove (Syzygium aromaticum) (SAE). This synthesis of green silver nanoparticles (AgNP) was a novel and effectual tool against the Newcastle Viral Disease (NDV). Syzygium aromaticum extract was used as reducing and stabilizing agent for synthesis of silver nanoparticles. AgNP were characterized using diversity of biophysical methods inclusive of Fourier transform infrared spectroscopy (FTIR), UV-VIS spectroscopy and Transmission electron microscopy (TEM) for morphology and size. Furthermore, XRD analysis confirmed the crystalline nature of the particles. In current investigations, the antiviral activity of clove buds silver nanoparticles was inspected in-vitro and in-ovo. Embryonated chicken eggs were used to perform the cytotoxicity assay of the clove extract silver nanoparticles (CESN). CESN showed in vitro antiviral activity against NDV in embryonated eggs.

Stability indicating RP-HPLC method of dexibuprofen in nanocream formulation: Identification and quantification.

A stability indicating reverse phase-HPLC method was designed for determination of dexibuprofen in drug solution and in nanocream formulation. Chromatographic conditions were optimized simply by adjusting the content and different compositions of reverse phase associated with mobile phases. Different parameters like specificity, limit of quantification (LOQ), limit of detection, linearity, range, system suitability, precision and accuracy were determined. Stability studies of dexibuprofen in nanocream were taken under the stressed situations of alkali, acid, oxidation process, UV and heat degradation. Tailing factor and % RSD were found >2000 and <2% respectively. The method was identified linear over the range of 0.2-1.6mg/ml having co-efficient of correlation 0.9995. Intra-day and inter- day precision and accuracy values for dexibuprofen were < 0.6% and <1.1032 and < 0.3% and 1.10% respectively. Stability studies showed that dexibuprofen was stable in nanocream against alkali, acid, oxidation, UV light and heat. The developed validated method was precise and accurate for the evaluation of dexibuprofen in solution as well as in nanocream formulation.

Hepatoprotective and Renoprotective Properties of Lovastatin-Loaded Ginger and Garlic Oil Nanoemulsomes: Insights into Serum Biological Parameters.

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.

Development and validation of a stability-Indicating RP-HPLC method for simultaneous estimation of sofosbuvir and velpatasvir in fixed dose combination tablets and plasma.

A simple, specific, sensitive, robust, accurate and precise reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for simultaneous determination of sofosbuvir (SOF) and velpatasvir (VLP) in fixed dose combination tablets and plasma. Validation parameters, such as system suitability, accuracy, inter-day and intra-day variances, specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), robustness and stability were assessed following the standards set by the International Conference on Harmonization (ICH). The isocratic elution of SOF and VLP was carried out under ambient conditions using ammonium acetate buffer (pH = 7.0), acetonitrile and methanol (20:40:40, v/v/v) as mobile phase flowing through a Promosil C18 column at a flow rate of 1.0 mL/min. The average retention time of SOF and VLP was 3.72 min and 7.09 min, respectively. The LOD and LOQ of SOF were 0.23µg/mL and 2.48µg/mL, respectively; while those of VLP were 0.70µg/mL and 7.52µg/mL, respectively. The regression coefficient (r2) was 0.998. The relative standard deviation (RSD) was less than 2% for precision. The recovery of both the analytes remained within 100±1%. All other validation parameters complied with ICH guidelines. The analytes remained stable throughout the analytical procedure. Moreover, this method was successfully applied to assess the in vitro dissolution of SOF and VLP loaded fixed dose combination tablets. Same method with same mobile phase was applied on rat plasma and there was no interference.

Facile synthesis of mesoporous silica nanoparticles using modified sol-gel method: Optimization and in vitro cytotoxicity studies.

The present study describes the synthesis of mesoporous silica nanoparticles using a modified sol-gel method. Various proportions of acetonitrile-water mixtures were utilized so as to optimize the reaction mixture for facile synthesis of mesoporous silica nanoparticles with controlled particle size for the very first time. After carefully adjusting the water and acetonitrile contents i.e. to 1:1 v/v ratio, a more uniform and small sized nanoparticles were achieved. The resultant particles were 140 nm in size having pore size of approximately 5.9 nm and were safe to be used in the cellular system, as confirmed by the in vitro cytotoxicity studies.

Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis.

Flurbiprofen, an NSAID, is a water insoluble drug that is also notorious for gastric irritation and inflammation. This study was aimed at using a natural gastrprotective oil as the internal phase to develop flurbiprofen micro emulsion (ME) to improve it solubility and ameliorate its gastric side effects. Upon screening of ME components for drug solubility, clove oil, tween 80 and transcutol were identified as the oil, surfactant and co surfactant, respectively, with higher flurbiprofen solubility. Pseudo-ternary phase diagrams revealed that the ME made with surfactant only and without co-surfactant displayed the similar ME region as made with the mixture of surfactant and co-surfactant. Furthermore, drug loaded oil was also used to draw pseudo-ternary phase diagram and a very little decrease in the ME region was observed. Therefore, co-surfactant free flurbiprofen loaded ME was developed to avoid side effects associated with the use of excessive surfactant quantities. ME were found to possess size in the range of 11-41 nm with PDI <0.5 and a slightly negative charge. Conductivity, pH and refractive indices of the selected MEs were well in the range. Drug release studies indicated maximum drug release from MEs within 5 min. Analysis of the gastric mucosa of rats after oral administration of drug solution and drug loaded ME confirmed that clove oil based ME provided significant protection against the NSAIDs induced gastric damage.

Crosslinked PVA-g-poly(AMPS) Nanogels for Enhanced Solubility and Dissolution of Ticagrelor: Synthesis, Characterization, and Toxicity Evaluation.

In this study, we synthesized PVA-g-poly(AMPS) nanogels with the aim of enhancing the solubility and dissolution of ticagrelor (TGR). Ticagrelor, a noncompetitive, reversible P2Y12 receptor antagonist, is prescribed to treat acute coronary syndrome. Ticagrelor has restricted oral bioavailability (≈36%) because of its poor solubility and permeability. The free radical polymerization methodology was employed to synthesize nanogels with varied concentrations of poly(vinyl alcohol) (polymer), 2-acrylamido-2-methylpropanesulfonic acid (monomer), and N,N-methylene bis(acrylamide) (crosslinker). The prepared nanogels were analyzed by swelling studies, % drug entrapment efficiency (DEE), solubility studies, in vitro drug release studies, zeta sizer, Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The optimized formulation (PA5) revealed a particle size of 45.86 nm, with a polydispersity index (PDI) of 0.41 and a %DEE of 85.1%. FTIR spectroscopy, XRD, and SEM confirmed the formation of crosslinked nanogels with amorphous and porous structures, and TGA/DSC proved their thermal stability. In vitro dissolution studies showed 99.91% drug release, and the ticagrelor solubility from the synthesized formulations was significantly improved up to 8.2-fold. All formulations followed the Korsmeyer-Peppas model with the Fickian diffusion as the release mechanism. The toxicity studies carried out on rats and the MTT assay on the Caco-2 cell line validated the biocompatibility of the nanogel formulations. The outcomes of the current study led to the conclusion that the PVA-g-poly(AMPS) nanogels synthesized by us could be used as dedicated pharmaceutical delivery systems to achieve enhanced solubility and dissolution of ticagrelor.

Topical Delivery of Terbinafine HCL Using Nanogels: A New Approach to Superficial Fungal Infection Treatment.

This study investigated pH-responsive Terbinafine HCL (TBH)-loaded nanogels as a new approach to treating superficial fungal infections. Acrylic acid (AA) is a synthetic monomer that was crosslinked with a natural polymer (gelatin) using a free radical polymerization technique to fabricate gelatin-g-poly-(acrylic acid) nanogels. Ammonium persulphate (APS) and N, N'-methylene bisacrylamide (MBA) were used as the initiator and crosslinker, respectively. Developed gelatin-g-poly-(acrylic acid) nanogels were evaluated for the swelling study (pH 1.2, 5, 7.4), DEE, particle size, FTIR, thermal stability (TGA, DSC), XRD, SEM, DEE, and in vitro drug release study to obtain optimized nanogels. Optimized nanogels were incorporated into 1% HPMC gel and then evaluated in comparison with Lamisil cream 1% for TBH stratum corneum retention, skin irritation, and in vitro and in vivo antifungal activity studies. Optimized nanogels (AAG 7) demonstrated a 255 nm particle size, 82.37% DEE, pH-dependent swelling, 92.15% of drug release (pH) 7.4 within 12 h, and a larger zone of inhibition compared to Lamisil cream. HPMC-loaded nanogels significantly improved the TBH skin retention percentage, as revealed by an ex vivo skin retention study, indicating the usefulness of nanogels for topical use. In vivo studies conducted on animal models infected with a fungal infection have further confirmed the effectiveness of nanogels compared with the Lamisil cream. Hence, Gelatin-g-poly-(acrylic acid) nanogels carrying poorly soluble TBH can be a promising approach for treating superficial fungal infections.

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.

Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes.

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of ß-cyclodextrin (ßCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with ßCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with ßCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: ßCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:ßCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: ßCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

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.].

Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen.

The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98-100% of drug release in 30-45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

Synthesis and Evaluation of Polyethylene Glycol-4000-Co-Poly (AMPS) Based Hydrogel Membranes for Controlled Release of Mupirocin for Efficient Wound Healing.

BACKGROUND: Chronic wound healing is a major challenge for the health care system around the globe. The current study was conducted to develop and characterize chemically cross-linked polyethylene glycol-co-poly (AMPS) hydrogel membranes to enhance the wound healing efficiency of antibiotic mupirocin (MP). METHODS: Free radical polymerization technique was used to develop hydrogel membranes. In an aqueous medium, polymer PEG-4000 was cross-linked with the monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) in the presence of initiators ammonium peroxide sulfate (APS) and sodium hydrogen sulfite (SHS). N, N-Methylene-bis-acrylamide (MBA) was used as a cross-linker in preparing hydrogel membranes. Developed membranes were spherical, transparent, and had elasticity. FTIR, TGA/DSC, and SEM were used to characterize the polymeric system. Swelling behavior, drug loading, and release pattern at pH of 5.5 and 7.4, irritation study, ex vivo drug permeation, and deposition study were also evaluated. RESULTS: Formed membranes were spherical, transparent, and had elasticity. The formation of a stable polymeric network was confirmed by structural and thermal analysis. Evaluation of the drug permeability in the skin showed good permeation and retention capabilities. No irritancy to the skin was observed. CONCLUSION: Based on the results obtained, the present study concluded that the formulated stable network might be an ideal network for the delivery of mupirocin in skin infections.

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.

Evaluation of Low Molecular Weight Cross Linked Chitosan Nanoparticles, to Enhance the Bioavailability of 5-Flourouracil.

The present study aimed to formulate 5-fluorouracil loaded cross linked chitosan nanoparticles based on chemical cross-linking of low molecular weight chitosan with glutaraldehyde by reverse micelles technique as 5-FU is less hydrophobic, relatively potent, has a shorter half-life, is rapidly metabolized, less tolerated, and has low oral bioavailability; therefore, we aimed to formulate potential nanocarriers of 5-FU for efficient drug delivery to specific targeted areas of action, reduce oral toxicity, improve tolerability and therapeutic outcomes of 5-FU, in a restricted fashion to enhance the bioavailability of 5-FU. Nanoparticles were formulated by the reverse micelle method based on the chemical cross-linking of glutaraldehyde (25% aqueous solution) into a w/o emulsion in different ratios. LMWCH-NPs were characterized for post-formulation parameters by mean particle size, zeta potential, %age yield, loading/entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), DSC/TGA, TEM, PXRD, drug release at pH 1.2, and pH 7.4. 5-FU loaded NPs showed a size range (198 nm-200 nm) and zeta potential (-39mV to -41mV), which ensured mechanical stability and increased retention time in blood vessels by the sustained release properties of biodegradable nanocarrier drug delivery systems. % age yield showed the range 92% to 96% while % LC ranged 2.0% to 3.4% and %EE ranged 40% to 43%. The TEM images showed spherical nanoparticles. FTIR revealed the compatibility between the drug and the cross-linked polymer. DSC/TGA ensured the thermal stability of the drug, while the solid-state stability of the drug-loaded cross-linked chitosan nanoparticles was evaluated by powder X-ray diffraction (PXRD) analysis. Drug release studies were performed using the dialysis bag technique at both pH (1.2 and 7.4) to mimic the gastrointestinal tract. Highly stable NPs displayed targeted release in phosphate buffer pH 7.4 at 37°C. Fickian diffusion was the predominant release with an R2 value of 0.9975-0.9973-and an N value 0.45-0.53. Prepared nanoparticles are inert, biodegradable, and biocompatible drug delivery systems for sustained release of 5-FU with maximum therapeutic efficacy and bioavailability.

Optimization, in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks.

BACKGROUND: In recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher's attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue. METHODS: Here, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL. RESULTS: Optimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum. CONCLUSION: Conclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.