Novel insights into the anti-asthmatic effect of Raphanus sativus L. (Raphani Semen): Targeting immune cells, inflammatory pathways and oxidative stress markers.

ETHNOPHARMACOLOGICAL RELEVANCE: Raphanus sativus L. is a well-known medicinal plant with traditional therapeutic applications in various common ailments including inflammation and asthma. AIMS OF THE STUDY: This study aimed to evaluate the chemical composition and anti-asthmatic potential of the hydro-methanolic extract of the leaves of R. sativus L. (Rs.Cr) using various in vitro and in vivo investigations. MATERIALS AND METHODS: The Rs.Cr was subjected to preliminary phytochemical analysis and HPLC profiling. The safety was assessed through oral acute toxicity tests in mice. The antiasthmatic effect of the extract was studied using milk-induced leukocytosis and ovalbumin (OVA)-induced allergic asthma models established in mice. While mast cell degranulation and passive paw anaphylaxis models were established in rats. Moreover, effect of the extract was studied on various oxidative and inflammatory makers. The antioxidant effect of the extract was also studied by in vitro DPPH method. RESULTS: The HPLC profiling of Rs.Cr showed the presence of important polyphenols in a considerable quantity. In toxicity evaluation, Rs.Cr showed no sign of morbidity or mortality with LD50 < 2000 mg/kg. The extract revealed significant mast cell disruption in a dose-dependent manner compared to the intoxicated group. Similarly, treatment with Rs.Cr and dexamethasone significantly (p < 0.001) reduced paw edema volume. Subcutaneous injection of milk at a dose of 4 mL/kg, after 24 h of its administration, showed an increase in the leukocyte count in the intoxicated group. Similarly, mice treated with dexamethasone and Rs.Cr respectively showed a significant decrease in leukocytes and eosinophils count in the ovalbumin-induced allergic asthma model. The extract presented a significant (p˂0.001) alleviative effect on the levels of SOD and GSH, MDA, IL-4, IL-5, and IL-13 in a dose-dependent manner as compared to the intoxicated group. Furthermore, the histological evaluation also revealed a notable decrease in inflammatory and goblet cell count with reduced mucus production. CONCLUSION: The current study highlights mechanism-based novel insights into the anti-asthmatic potential of R. sativus that also strongly supports its traditional use in asthma.

Effect of digestible protein on intermediate metabolism, hepatic enzyme activities, energy reserves, and growth performance of pacu (Piaractus mesopotamicus) in the finishing growth phase.

This study investigated the effect of different levels of digestible protein (DP) on blood metabolites, hepatic enzyme activity of glycolysis and amino acid metabolism, energy reserves, and the production characteristics of pacu (Piaractus mesopotamicus) during the finishing growth phase. Six semi purified and isoenergetic diets, containing 16.3, 20.1, 23.8, 27.2, 31.5, and 34.8% of balanced DP, provided with essential amino acid balance, were hand-fed to pacu (1100.0 ± 10.3 g, initial weight) three times daily for 7 weeks. The experiment consisted of six treatments, with three randomly arranged replicates (tanks) per treatment. The data obtained from this experiment were analyzed by one-way analysis of variance (ANOVA), and significant differences (p < 0.05) between treatments were determined using Tukey's test. Blood metabolites, except serum ammonia and the hepatic enzymes activities of glycolysis and amino acid metabolism, except hexokinase activity were affected (p < 0.05) by balanced DP. The energy reserve indices, except hepatic total lipid content, were also found associated (p < 0.05) with balanced DP. The test diets significantly (p < 0.05) affected growth performance parameters. Higher dietary proteins led to a greater energy uptake by fish from the protein in feed. Overall, fish fed the intermediate level (23.8%) of balanced DP with digestible energy of 17.95 MJ kg-1 showed better production traits and physio-biochemical health markers. This information could help nutritionists and farmers to develop nutritionally balanced and economically and environmentally sustainable aquafeed for promoting healthy and sustainable production of pacu in intensive culture systems.

Fabrication, organoleptic evaluation and in vitro characterization of cream loaded with Carica papaya seed extract.

OBJECTIVE: The current study aimed to provide preliminary insights into potential biopharmaceutical applications of Carica papaya seed extract by evaluating its phytochemical and biological profiles. Furthermore, the study aimed to develop a stable oil-in-water (O/W) emulsion for the effective delivery of antioxidant-rich biologicals for cosmetic purposes. METHODS: The hydroethanolic (ethanol 80%: 20% water) extract of C. papaya seeds was prepared via maceration technique. The chemical composition was carried out through preliminary phytochemical screening and estimation of total phenolic contents (TPC) and total flavonoid contents (TFC). The biological profile of the extract was explored using various in-vitro antioxidant methods. The homogenization procedure was used to create a cream of O/W and various tests were applied to assess the stability of the emulsion. By keeping the emulsion at different storage conditions (8 ± 0.5°C, 25 ± 0.5°C, 40 ± 0.5°C, and 40 ± 0.5°C ± 75% relative humidity [RH]) for a period of 28 days), the physical stability parameters of the emulsion, including pH, viscosity, centrifugation, phase separation, and conductivity, as well as rheological parameters and organoleptic parameters (odor, color, liquefaction, and creaming), were assessed. RESULTS: The preliminary phytochemical screening assay revealed the presence of various plant secondary metabolites including alkaloids, phenolics, flavonoids, tannins, saponins, and quinones. The extract was found to be rich in TPC and TFC. The in vitro antioxidant study gave maximum activity in the DPPH method. The plant extract containing cosmetic cream exhibited remarkable stability during the entire research. Data gathered indicated that no phase separation or liquefaction was seen after the experimental period. Throughout the experimental period, a small variation in the pH and conductivity values of the base and formulation was seen. CONCLUSION: The findings suggest that the seed extract of C. papaya is a rich source of polyphenols with antioxidant potential and can be a promising alternative for the treatment of various ailments. The stability of emulsion paves the way for its utilization as a carrier for the delivery of 3% C. papaya seed extract and applications in cosmetics products.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. AIMS OF THE STUDY: This study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. METHODOLOGY: The hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FINDINGS: The phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 µg/mL and 139.05 µg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. CONCLUSION: This report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Evaluating the Aphrodisiac Potential of Mirabilis jalapa L. Root Extract: Phytochemical Profiling and In Silico, In Vitro, and In Vivo Assessments in Normal Male Rats.

The traditional use of Mirabilis jalapa L. roots to enhance male sexual performance prompted us to assess the in silico, in vitro, and in vivo aphrodisiac activities of its hydroethanolic extract using normal male rats. Spectroscopic characterization indicated the presence of ß-D-glucopyranoside, methyl-1,9-benzyl-2,6-dichloro-9H-purine, and Bis-(2-ethylhexyl)-phthalate; these compounds have a significant inhibitory effect on the phosphodiesterase-5 (PDE-5) enzyme in silico evaluation and minerals (including zinc, cadmium, and magnesium). Other phytochemical analyses revealed the presence of phenolic compounds and flavonoids. These phytochemicals and minerals may contribute to the aphrodisiac activities of the extract. Additionally, the in vivo study revealed that the administration of M. jalapa root extract (300 mg/kg) significantly enhanced (p < 0.01, p < 0.03) mount, intromission, and ejaculation frequencies while significantly (p < 0.05) decreasing the mount and intromission latencies, as well as the post-ejaculatory interval time, in comparison with the standard drugs sildenafil and ginseng, resulting in enhanced erection and sexual performance in the rats. Furthermore, the extract significantly (p < 0.05) increased penile reflexes and also elevated the levels of testosterone and luteinizing hormones. Extract (300 mg/kg) significantly (p < 0.05) inhibited the PDE-5 enzyme in an in vitro study. Concludingly, the comprehensive findings of this study suggest that a standardized herbal extract derived from M. jalapa roots alleviates erectile dysfunction and premature ejaculation in male rats. M. jalapa root extract proved to be an alternative treatment for erectile dysfunction and premature ejaculation.

EHHR: an efficient evolutionary hyper-heuristic based recommender framework for short-text classifier selection.

With various machine learning heuristics, it becomes difficult to choose an appropriate heuristic to classify short-text emerging from various social media sources in the form of tweets and reviews. The No Free Lunch theorem asserts that no heuristic applies to all problems indiscriminately. Regardless of their success, the available classifier recommendation algorithms only deal with numeric data. To cater to these limitations, an umbrella classifier recommender must determine the best heuristic for short-text data. This paper presents an efficient reminisce-enabled classifier recommender framework to recommend a heuristic for new short-text data classification. The proposed framework, "Efficient Evolutionary Hyper-heuristic based Recommender Framework for Short-text Classifier Selection (EHHR)," reuses the previous solutions to predict the performance of various heuristics for an unseen problem. The Hybrid Adaptive Genetic Algorithm (HAGA) in EHHR facilitates dataset-level feature optimization and performance prediction. HAGA reveals that the influential features for recommending the best short-text heuristic are the average entropy, mean length of the word string, adjective variation, verb variation II, and average hard examples. The experimental results show that HAGA is 80% more accurate when compared to the standard Genetic Algorithm (GA). Additionally, EHHR clusters datasets and rank heuristics cluster-wise. EHHR clusters 9 out of 10 problems correctly.

Carbopol Based Hydrogels for ITOPRIDE Hydrochloride Delivery; Synthesis, Characterization and Comparative Assessment with Various Monomers.

The objective of the current study was to synthesize and characterize carbopol containing hydrogels with different monomers such as methacrylic acid (MAA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and itaconic acid (ITA). Free radical polymerization method was optimized for the preparation of different formulations using N,N-methylene bis-acrylamide (MBA) as cross linking agent. Different studies were performed to evaluate the effect of different monomers on swelling, drug loading and drug release. Itopride Hydrochloride was used as model drug. FTIR, TGA, DSC and SEM were performed to probe the characteristics of fabricated hydrogels. Swelling studies of different fabricated hydrogels were performed in three pH conditions (1.2, 4.5 & 6.8). Higher swelling was observed at pH 6.8. An in-vitro release study was performed on pH 1.2 and 6.8. The synthesized hydrogels exhibited excellent mechanical strength, higher drug loading, pH sensitive and time dependent release up to 30 h. The excellent mechanical strength and extended drug release of Carbopol-co-poly-MAA-ITA hydrogels make them a potential candidate for controlled delivery of Itopride hydrochloride.

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.

Synthesis and Evaluation of Finasteride-Loaded HPMC-Based Nanogels for Transdermal Delivery: A Versatile Nanoscopic Platform.

Herein, we report nanogels comprising diverse feed ratio of polymer hydroxypropyl methylcellulose (HPMC), monomer acrylic acid (AA), and cross-linker methylene bisacrylamide (MBA) fabricated for transdermal delivery of finasteride (FIN). Free radical solution polymerization method with subsequent condensation was employed for the synthesis using ammonium per sulfate (APS) and sodium hydrogen sulfite (SHS) as initiators. Carbopol-940 gel (CG) was formulated as assisting platform to deliver FIN nanogels transdermally. Developed formulations were evaluated by several in vitro, ex vivo, and in vivo parameters such as particle size and charge distribution analysis, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffractogram (XRD), rheological testing, in vitro swelling and drug release, and ex vivo skin permeation, irritation, and toxicity assessment. The results endorsed the nanogel formation (117.3 ± 29.113 nm), and the impact of synthesizing method was signified by high yield of nanogels (≈91%). Efficient response for in vitro swelling and FIN release was revealed at pH 5.5 and 7.4. Skin irritation and toxicity assessment ensured the biocompatibility of prepared nanocomposites. On the basis of the results obtained, it can be concluded that the developed nanogels were stable with excellent drug permeation profile across skin.

Development of mucus-penetrating iodine loaded self-emulsifying system for local vaginal delivery.

The major goal of this project was to formulate iodine-based self nano-emulsifying drug delivery system to provide improve antimicrobial activity and enhanced mucosal residence time via mucus penetration. Iodine SNEDDS (Self nano-emulsifying drug delivery system) with different concentration were formulated using castor oil as the oil phase, cremophor ethoxylated (CrEL) as a surfactant and after screening a number of vehicles, PEG 400 was employed as co-surfactant. Self-emulsification time, thermodynamic stability tests, robustness to dilution, percent transmittance, droplet size, and drug release were measured. Ternary phase diagrams were plotted to determine the area of emulsification. When compared to the commercial formulation, dissolving experiments revealed that the iodine from the SNEDDS enhanced aqueous solubility. In-vitro iodine release was determined to be around 15% per hour, with muco-adhesive and, muco-penetrating characteristics showing a 38-fold improvement. Furthermore, SNEDDS demonstrated significant antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Similarly, when compared to marketed drugs, in-vitro drug absorption profile from the manufactured SNEDDS shown to be much higher. According to these results iodine containing SNEDDS could be a useful new formulation for iodine mucosal usage.

Highly Responsive Chitosan-Co-Poly (MAA) Nanomatrices through Cross-Linking Polymerization for Solubility Improvement.

In this study, we report the highly responsive chitosan-based chemically cross-linked nanomatrices, a nano-version of hydrogels developed through modified polymerization reaction for solubility improvement of poorly soluble drug simvastatin. The developed nanomatrices were characterized for solubilization efficiency, swelling studies, sol-gel analysis, in vitro drug release studies, DSC, FTIR, XRD, SEM, particle size analysis, and stability studies. An in vivo acute toxicity study was conducted on female Winstor rats, the result of which endorsed the safety and biocompatibility of the system. A porous and fluffy structure was observed under SEM analysis, which supports the great swelling tendency of the system that further governs the in vitro drug release. Zeta sizer analyzed the particle size in the range of 227.8 ± 17.8 nm. Nano sizing and grafting of hydrophilic excipients to the nanomatrices system explains this shift of trend towards the enhancement of solubilization efficiency, and, furthermore, the XRD results confirmed the amorphous nature of the system. FTIR and DSC analysis confirmed the successful grafting and stability to the system. The developed nanomatrices enhanced the release characteristics and solubility of simvastatin significantly and could be an effective technique for solubility and bioavailability enhancement of other BCS class-II drugs. Due to enhanced solubility, efficient method of preparation, excellent physico-chemical features, and rapid and high dissolution and bio-compatibility, the developed nanomatrices may be a promising approach for oral delivery of hydrophobic drugs.

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.

Synthesis and Characterization of Carboxymethyl Chitosan Nanosponges with Cyclodextrin Blends for Drug Solubility Improvement.

This study aimed to enhance the solubility and release characteristics of docetaxel by synthesizing highly porous and stimuli responsive nanosponges, a nano-version of hydrogels with the additional qualities of both hydrogels and nano-systems. Nanosponges were prepared by the free radical polymerization technique and characterized by their solubilization efficiency, swelling studies, sol-gel studies, percentage entrapment efficiency, drug loading, FTIR, PXRD, TGA, DSC, SEM, zeta sizer and in vitro dissolution studies. In vivo toxicity study was conducted to assess the safety of the oral administration of prepared nanosponges. FTIR, TGA and DSC studies confirmed the successful grafting of components into the stable nano-polymeric network. A porous and sponge-like structure was visualized through SEM images. The particle size of the optimized formulation was observed in the range of 195 ± 3 nm. The fabricated nanosponges noticeably enhanced the drug loading and solubilization efficiency of docetaxel in aqueous media. The drug release of fabricated nanosponges was significantly higher at pH 6.8 as compared to pH 1.2 and 4.5. An acute oral toxicity study endorsed the safety of the system. Due to an efficient preparation technique, as well as its enhanced solubility, excellent physicochemical properties, improved dissolution and non-toxic nature, nanosponges could be an efficient and a promising approach for the oral delivery of poorly soluble drugs.

Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs.

Poor aqueous solubility and poor bioavailability are major issues with many pharmaceutical industries. By some estimation, 70-90% drug candidates in development stage while up-to 40% of the marketed products are poorly soluble which leads to low bioavailability, reduced therapeutic effects and dosage escalation. That's why solubility is an important factor to consider during design and manufacturing of the pharmaceutical products. To-date, various strategies have been explored to tackle the issue of poor solubility. This review article focuses the updated overview of commonly used macro and nano drug delivery systems and techniques such as micronization, solid dispersion (SD), supercritical fluid (SCF), hydrotropy, co-solvency, micellar solubilization, cryogenic technique, inclusion complex formation-based techniques, nanosuspension, solid lipid nanoparticles, and nanogels/nanomatrices explored for solubility enhancement of poorly soluble drugs. Among various techniques, nanomatrices were found a promising and impeccable strategy for solubility enhancement of poorly soluble drugs. This article also describes the mechanism of action of each technique used in solubilization enhancement.

Bi-polymeric Spongy Matrices Through Cross-linking Polymerization: Synthesized and Evaluated for Solubility Enhancement of Acyclovir.

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (ß-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-ßCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-ßCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.

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.

A difunctional Pluronic®127-based in situ formed injectable thermogels as prolonged and controlled curcumin depot, fabrication, in vitro characterization and in vivo safety evaluation.

Curcumin has been reported to be used widely against many types of pathological conditions in clinics. However, due to its limitations such as poor solubility, poor oral absorption and low stability have limited its applications. In the current study, a series of novel chemically cross-linkable depot gel formulations were developed based on thermoresponsive micellar polymer (Pluronic®127) with polyelectrolyte hydrophilic monomer, that is, 2-acrylamido-2-methylpropane sulfonic acid by cold and in situ grafting polymerization method. The formulations were aimed to deliver curcumin at controlled rate from in situ formed depot after administration through subcutaneous route in vivo. The sol-gel phase transitions of formulations were observed by rheological analysis, tube titling and optical transmittance measurements. Maximum swelling of gel formulations was observed at pH 7.4 and below CGT, that is, 25 °C. The in vitro release profile exhibits maximum drug release at pH 7.4 and 25 °C owing to relaxed gel state. In vitro degradation profile of gel formulations showed controlled degradation rate. Cell growth inhibition study confirmed the biocompatibility and safe nature of bare gel formulations against L929 cell lines. In vitro cytotoxic study showed that curcumin loaded in gel formulation has controlled pharmacological activity against HeLa and MCF-7 cancer cells as compared to free drug solution. The IC50 values calculated for pure curcumin solution (30 ± 0.77 µg/ml for HeLa and 27 ± 0.39 µg/ml for MCF-7) were found higher in comparison to curcumin-loaded thermogels against HeLa (19 ± 0.28 µg/ml and 23 ± 0.81 µg/ml) and MCF-7 (22 ± 0.54 µg/ml and 21 ± 0.49 µg/ml). Histopathological and hematological analysis showed the biocompatible nature of hydrogels. Structural confirmation was done by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (1H NMR). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the thermal stability of the gel formulation. The porous structure of gel formulations was assessed by scanning electron microscopic (SEM) analysis. Results concluded that newly developed gel formulations have thermoresponsive behavior with phase transition at body temperature and can be used as in situ controlled drug depot.

Porous and highly responsive cross-linked ß-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption.

AIMS: Aim of the study was to enhance the solubility of Chlorthalidone by developing beta-cyclodextrin cross-linked hydrophilic nanomatrices. MAIN METHODS: Nine different formulations were fabricated by free radical polymerization technique. All formulations were characterized through different studies. FTIR spectroscopy of unloaded and loaded nanomatrices was processed to determine compatibility of constituents and that of the drug with the system. Surface morphology of the nanomatrices was studied by SEM. The size of the optimized formulation was determined by zeta sizer. Swelling, in-vitro release and solubility studies were carried out in different media and results of in-vitro release profiles of nanomatrices and commercially available tablet of Chlorthalidone were compared. For determination of biocompatibility, toxicity studies were proclaimed in rabbits. KEY FINDINGS: Main peaks of corresponding functional groups of individual constituents and that of drug were depicted in FTIR spectra of unloaded and loaded nanomatrices. Porous and fluffy structure was visualized through SEM images. Particle size of the optimized formulation was in the range of 175 ± 5.27 nm. Percent loading of optimized formulation showed the best result. Comparing the in-vitro drug release profiles of nanomatrices and commercially available tablet, the results of the synthesized nanomatrices were quite satisfactory. Solubility profiles were also high as compared to the drug alone. Moreover, toxicity studies confirmed that nanomatrices were biocompatible and no sign of any toxic effect was found. SIGNIFICANCE: We concluded that our developed nanomatrices had successfully enhanced the solubility of Chlorthalidone and can also be used for other poorly aqueous soluble drugs.