Subject(s)
Ion Exchange Resins/metabolism , Sodium/metabolism , Succinates/metabolism , Animals , Edema/etiology , Edema/therapy , Female , In Vitro Techniques , Ion Exchange , Ion Exchange Resins/adverse effects , Ion Exchange Resins/therapeutic use , Kidney Diseases/metabolism , Kidney Diseases/physiopathology , Potassium/metabolism , Rats , Rats, Inbred Strains , Succinates/adverse effects , Succinates/therapeutic useSubject(s)
Graft Rejection , Islets of Langerhans/immunology , Animals , Cell Membrane/immunology , Diffusion , Humans , Rats , Ultrafiltration/methodsABSTRACT
Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective against S. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi's equation up to approximately 80% release, with exponentially decreasing release rates thereafter.
Subject(s)
Antimony/administration & dosage , Lactic Acid , Organometallic Compounds , Schistosomiasis/drug therapy , Succimer/administration & dosage , Sulfhydryl Compounds/administration & dosage , Capsules , Humans , Lactates , Polyesters , Polymers , Schistosoma mansoni , Schistosomicides/administration & dosageABSTRACT
The systemic use of platelet inhibitors has been shown to improve vascular graft function. In this study a biodegradable coating of polymeric polylactic acid (PLA) containing a microparticulate suspension of aspirin (ASA) 30% by weight, was applied to the lumenal surface of small diameter vascular prostheses to reduce platelet deposition on canine implanted arterial grafts. USCI 4-mm ID Dacron internal velour grafts were used. Coated and contralateral noncoated (control) prostheses were implanted in canine carotid and femoral arteries. Graft performance was assessed by determination of aspirin elution rates, in vivo red cell subtracted 111indium-labeled platelet scans, and post implant platelet aggregation studies. Eighty percent of the aspirin in the coated grafts was released during the first 24 hr of perfusion and approximately 20% of the aspirin remained in grafts after 1 month. In vivo platelet scans documented less platelet deposition on ASA-coated grafts when compared to controls 2 and 24 hr post implant (P less than 0.01, P less than 0.05, respectively). There was no significant difference in platelet deposition on ASA-coated and control grafts at 2 weeks or 1 month post implant. Post implant platelet aggregation studies indicated systemic platelet inhibition for 4-5 days. It was concluded that aspirin incorporation in a polylactic acid coating applied to 4-mm ID vascular prostheses reduced the platelet affinity of Dacron grafts and exerted a temporary local and systemic platelet inhibiting effect.
