Dataset Information

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

ABSTRACT: Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.

SUBMITTER: Lo YL

PROVIDER: S-EPMC3907813 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

Lo Yu-Li YL Lin Yijun Y Lin Hong-Ru HR

International journal of molecular sciences 20131231 1

Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu ...[more]

PMID: 24384838

Similar Datasets

Project description:The selective application of insecticides is one of the cornerstones of integrated pest management (IPM) and management strategies for pest resistance to insecticides. The present work provides a comprehensive overview of the traditional and new methods for the application of gas, liquid, gel, and solid physical insecticide formulations to control stored-product and food industry urban pests from the taxa Acarina, Blattodea, Coleoptera, Diptera, Hymenoptera, Lepidoptera, Psocoptera, and Zygentoma. Various definitions and concepts historically and currently used for various pesticide application formulations and methods are also described. This review demonstrates that new technological advances have sparked renewed research interest in the optimization of conventional methods such as insecticide aerosols, sprays, fumigants, and inert gases. Insect growth regulators/disruptors (IGRs/IGDs) are increasingly employed in baits, aerosols, residual treatments, and as spray-residual protectants for long-term stored-grain protection. Insecticide-impregnated hypoxic multilayer bags have been proven to be one of the most promising low-cost and safe methods for hermetic grain storage in developing countries. Insecticide-impregnated netting and food baits were originally developed for the control of urban/medical pests and have been recognized as an innovative technology for the protection of stored commodities. New biodegradable acaricide gel coatings and nets have been suggested for the protection of ham meat. Tablets and satchels represent a new approach for the application of botanicals. Many emerging technologies can be found in the form of impregnated protective packaging (insect growth regulators/disruptors (IGRs/IGDs), natural repellents), pheromone-based attracticides, electrostatic dust or sprays, nanoparticles, edible artificial sweeteners, hydrogels, inert baits with synthetic attractants, biodegradable encapsulations of active ingredients, and cyanogenic protective grain coatings. Smart pest control technologies based on RNA-based gene silencing compounds incorporated into food baits stand at the forefront of current strategic research. Inert gases and dust (diatomaceous earth) are positive examples of alternatives to synthetic pesticide products, for which methods of application and their integration with other methods have been proposed and implemented in practice. Although many promising laboratory studies have been conducted on the biological activity of natural botanical insecticides, published studies demonstrating their effective industrial field usage in grain stores and food production facilities are scarce. This review shows that the current problems associated with the application of some natural botanical insecticides (e.g., sorption, stability, field efficacy, and smell) to some extent echo problems that were frequently encountered and addressed almost 100 years ago during the transition from ancient to modern classical chemical pest control methods.

Project description:Lessons learnedLimited evidence suggests an acceptable pharmacokinetic profile when enzalutamide is administered via a liquid formulation extracted from the commercially available liquid-filled soft-gelatin capsules. Tolerability may limit use in clinical practice.BackgroundEnzalutamide is an established standard-of-care treatment for advanced prostate cancer with a commercially available formulation that may be inconvenient for some patients. We proposed a study to evaluate the bioequivalence of a liquid formulation to provide an alternative method of administration.MethodsThis was a single-dose, randomized, open-label, two-way crossover pilot bioequivalence study to compare two oral formulations of enzalutamide: four enzalutamide 40 mg liquid-filled soft-gelatin capsules (commercially available) administered whole versus enzalutamide 160 mg liquid (extracted from capsules) administered via oral syringe. To assess bioequivalence, patients were randomized to receive a single dose of one formulation, then cross over to receive the alternative formulation following a 42-day washout period; serial plasma samples were collected over the course of 24 hours, followed by collections at 3, 8, and 42 days after the dose for both formulations. Bioequivalence of the formulations was assessed via comparisons of area under the plasma concentration-time curve (AUC) calculations per U.S. Food and Drug Administration (FDA) guidance. The study also assessed the safety and tolerability of the formulations.ResultsThe study failed to meet proposed accrual, with only one patient enrolled, thus limiting the bioequivalence evaluation. Based on the data from a single patient, the drug exposure (measured by AUC) of enzalutamide and N-desmethyl enzalutamide (primary active metabolite) for the liquid formulation was 112% and 117%, respectively, compared with the capsule formulation. Although both formulations appeared well tolerated with no adverse events reported, the tolerability assessment questionnaire revealed an unpleasant taste of the liquid formulation.ConclusionPreliminary evidence suggests a similar pharmacokinetic profile when administering liquid extracted from enzalutamide soft-gelatin capsules compared with intact capsules in patients with prostate cancer.

Project description:BackgroundModified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×10(8) TCID50 in a volume of 0.5mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration.Methods524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2×10(7) TCID50 in 0.1mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination.ResultsAmong the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P=0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P=0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting ≥6 months. After second vaccination Day (42-208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary objective) to the Liquid-SC group.ConclusionsTransitioning to a lyophilized formulation, which has a longer shelf life, will not negatively impact immunogenicity. In a situation where insufficient vaccine is available, ID vaccination could be used, increasing the number of available doses of vaccine in the SNS 5-fold (i.e., from 20 million to 100 million doses).

Dataset Information

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

Publications

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets