RESUMO
Drug-fortified cationic liposomes of 6methoxy2naphthylacetic acid (6MNA) were prepared and characterized by various techniques. The residence time of drug-fortified liposomes in joint cavity was evaluated by intra-articular (IA) administration of the radio-labeled (99mTc) liposomal formulation in the inflamed joints in rats. The cationic liposomal formulation composed of 6MNA (3) as an active agent, its double salt (4) with the lipid 1,2distearoylsnglycero3phosphoethanolamine (DSPE), and pharmaceutically acceptable excipients such as hydrogenated soyabean phospatidylcholine (HSPC) and 1,2dioleyloxy3trimethylammoniumpropane chloride (DOTAP) were developed using thin film hydration technique. The cryo-TEM analysis confirmed that the prepared optimized liposomal formulation (DFL-2) was a mixture of small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In addition, the TEM analysis confirmed that the prepared liposomes were of spherical in shape having liposome size in the range of 500-900â¯nm and zeta potential of about +30â¯mV. The developed cationic liposomes exhibited sustained release profile of payload of 6MNA for over >12â¯h and about five times higher retention in the inflamed animal joints after 24â¯h (by scintigraphy of the joints) as compared to the plain 6MNA solution when administered by IA route. The anti-inflammatory activity of prepared liposomal composition is evaluated by Freund's adjuvant induced arthritic model in rats. The liposomal formulation was well tolerated by all animals indicating good biocompatibility. Further, the cationic liposomal formulation treated group showed decreased erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in comparison to the control and the standard groups in the in vivo study. The improved efficacy of the drug-fortified liposomal formulation was due to the coupled effect of longer retention and sustained release of the active drug 6MNA in the joints. From the obtained results it could be concluded that the combined effect of the cationic charge on the drug-fortified liposomes and the inherent affinity of the active agent towards the synovial joint tissues, coupled with slow release of the active drug due to double salt approach at the site of administration could potentially decrease the frequency of IA drug administration. Hence such a formulation could prove to be a therapeutic boon for the management of late stage arthritis.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Experimental/tratamento farmacológico , Ácidos Naftalenoacéticos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Monoinsaturados/farmacocinética , Lipossomos , Masculino , Camundongos , Células NIH 3T3 , Ácidos Naftalenoacéticos/farmacocinética , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/farmacocinética , Fosfatidiletanolaminas/administração & dosagem , Fosfatidiletanolaminas/farmacocinética , Compostos de Amônio Quaternário/administração & dosagem , Compostos de Amônio Quaternário/farmacocinética , Ratos Sprague-DawleyRESUMO
The present study describes an advanced biorefinery model for marine macroalgae that assumes significant importance in the context of marine bio-economy. The method investigated in this study integrates the extraction of crude proteins with recovery of minerals rich sap, lipids, ulvan and cellulose from fresh biomass of Ulva lactuca. The protein content extracted was 11±2.12% on dry weight basis with recovery efficiency of 68.75±4.01%. The amino acid composition of crude protein fraction showed iso-leucine as the most abundant amino acid with 16.51±0.03% followed by histidine, arginine, tyrosine, serine, aspartic acid, threonine, phenyl alanine, leucine, alanine, lysine, glycine and glutamic acid (0.22±0.24%). The digestibility of protein was as high as 85.86±5.92% indicating its suitability for use in food supplements. The protein production with co-recovery of other products would not only result in effective utilisation marine macroalgal resources but also forms the basis for marine bio-economy.