In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Abstract

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Carboranyl Analogues of Mefenamic Acid and Their Biological Evaluation

“…It is used for treatment of muscular aches, menstrual cramps, headache, dental pain, and as a painkiller after surgeries. 1 − 3 Based on its structure, mefenamic acid is a derivative of N -aryl anthranilic acid and it belongs to the class of fenamic acids. 4 − 6 Like many NSAIDs, mefenamic acid binds to cyclooxygenase (COX) and thus inhibits the synthesis of prostaglandins.…”

“…Mefenamic acid ( 1 , Scheme ) is a nonsteroidal anti-inflammatory drug (NSAID) with a wide range of pharmacological activities such as analgesic, anti-inflammatory, and antipyretic activity. It is used for treatment of muscular aches, menstrual cramps, headache, dental pain, and as a painkiller after surgeries. − Based on its structure, mefenamic acid is a derivative of N -aryl anthranilic acid and it belongs to the class of fenamic acids. − Like many NSAIDs, mefenamic acid binds to cyclooxygenase (COX) and thus inhibits the synthesis of prostaglandins.…”

Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

“…Several studies have demonstrated that the liposomal drug delivery system can enhance the therapeutic efficacy and reduce drug toxicities, which were attributed to their ability to enhance the bioavailability of poorly water-soluble drugs [ 14 , 15 , 16 , 17 , 18 ]. Liposomes can improve the bioavailability of drugs generally by enhancing their absorption, protecting the drugs from rapid metabolism, and prolonging biological half-life [ 19 ].…”

“…Several studies have demonstrated that the liposomal drug delivery system can enhance the therapeutic efficacy and reduce drug toxicities, which were attributed to their ability to enhance the bioavailability of poorly water-soluble drugs [14][15][16][17][18]. Liposomes can improve the bioavailability of Several studies have demonstrated that the liposomal drug delivery system can enhance the therapeutic efficacy and reduce drug toxicities, which were attributed to their ability to enhance the bioavailability of poorly water-soluble drugs [14][15][16][17][18]. Liposomes can improve the bioavailability of drugs generally by enhancing their absorption, protecting the drugs from rapid metabolism, and prolonging biological half-life [19].…”