Species-Specific in vitro and in vivo Evaluation of Toxicity of Silver Nanoparticles Stabilized with Gum Arabic Protein.

INTRODUCTION: We report, herein, in vitro, and in vivo toxicity evaluation of silver nanoparticles stabilized with gum arabic protein (AgNP-GP) in Daphnia similis, Danio rerio embryos and in Sprague Dawley rats. PURPOSE: The objective of this investigation was to evaluate in vitro and in vivo toxicity of silver nanoparticles stabilized with gum arabic protein (AgNP-GP), in multispecies due to the recognition that toxicity evaluations beyond a single species reflect the environmental realism. In the present study, AgNP-GP was synthesized through the reduction of silver salt using the tri-alanine-phosphine peptide (commonly referred to as "Katti Peptide") and stabilized using gum arabic protein. METHODS: In vitro cytotoxicity tests were performed according to ISO 10993-5 protocols to assess cytotoxicity index (IC50) values. Acute ecotoxicity (EC50) studies were performed using Daphnia similis, according to the ABNT NBR 15088 protocols. In vivo toxicity also included evaluation of acute embryotoxicity using Danio rerio (zebrafish) embryos following the OECD No. 236 guidelines. We also used Sprague Dawley rats to assess the toxicity of AgNP-GP in doses from 2.5 to 10.0 mg kg-1 body weight. RESULTS: AgNP-GP nanoparticles were characterized through UV (405 nm), core size (20±5 nm through TEM), hydrodynamic size (70-80 nm), Zeta (ζ) potential (- 26 mV) using DLS and Powder X ray diffraction (PXRD) and EDS. PXRD showed pattern consistent with the Ag (1 1 1) peak. EC50 in Daphnia similis was 4.40 (3.59-5.40) µg L-1. In the zebrafish species, LC50 was 177 µg L-1. Oral administration of AgNP-GP in Sprague Dawley rats for a period of 28 days revealed no adverse effects in doses of up to 10.0 mg kg-1 b.w. in both male and female animals. CONCLUSION: The non-toxicity of AgNP-GP in rats offers a myriad of applications of AgNP-GP in health and hygiene for use as antibiotics, antimicrobial and antifungal agents.

Topical dosage form of valdecoxib: preparation and pharmacological evaluation.

Valdecoxib, a selective COX-2 inhibitor, produces serious side effects when given orally. This has led to its withdrawal. Topical application of valdecoxib was formulated and evaluated for its efficacy and safety. Standard procedures were followed and male Wistar albino rats were used to test the anti-inflammatory effect and effect in hyperalgesic conditions. Ointments, creams, and gels containing valdecoxib 1% (m/m) were prepared. These were tested for physical appearance, pH, spreadability, drug content uniformity, in vitro diffusion. Gel prepared using Carbopol 940 (F-X) was selected after the analysis of the results. Formulation F-X was evaluated for acute skin irritancy, anti-inflammatory effect, optimum effective concentration of valdecoxib, effect on hyperalgesia, inhibition of the granulation tissue formation and anti-arthritic effect. Determination of valdecoxib in test animals plasma and determining the blood clotting time and bleeding time were conducted to study the safety of topical valdecoxib. Valdecoxib gel containing 1% (m/m) of the drug was significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to placebo gel, but exhibited significantly (p < 0.05) lower suppression of inflammation than commercial rofecoxib gel. Concentration of valdecoxib used in the preparation minimizes the risk of systemic effects, as shown by the analysis of rat plasma for the presence of valdecoxib; hence, this may be the alternative to oral preparations. The bleeding and clotting time showed no significant difference before and after application of F-X.