ABSTRACT
The possibility of use of polyhydroxyalkanoates (PHAs), biodegradable microbial polyesters, as a carrier for pesticides (alpha-hexachlorocyclohexane and lindane) for targeted and controlled delivery of these compounds to soil was investigated. The kinetics of polymer degradation and the dynamics of pesticide release from the extended-release formulations was studied. It is shown that pesticides embedded in a degradable polymer (PHA) carrier are released gradually and slowly, without surges, as the polymer is degraded by the soil microflora. The microbial soil component actively responded to the addition of the polymer as an additional nutrient substrate: the latter was degraded and then utilized. The rate of the pesticide release to the soil can be regulated by varying the polymer-pesticide ratio.
Subject(s)
Drug Carriers/chemistry , Hexachlorocyclohexane/chemistry , Pesticides/chemistry , Polyhydroxyalkanoates/chemistry , Soil Microbiology , Soil , Drug Carriers/pharmacology , Hexachlorocyclohexane/pharmacology , Pesticides/pharmacology , Polyhydroxyalkanoates/pharmacology , Time FactorsABSTRACT
Microparticles obtained by using (14)C-labeled resorbable hydroxyaminobutyric acid polymer were injected into the caudal vein of laboratory animals without negative aftereffects for their growth and development and without changes in the macro- and microstructure of organs and tissues. The distribution of microparticles in the viscera and the dynamics of accumulation of carbon-containing polymer degradation products in the viscera were studied. The main targets for the particles are liver tissues, as well as renal and splenic tissues. The polymeric matrix of the microparticles is most actively destroyed in the spleen and liver. The presence of high-molecular-weight polymeric matrix in organs indicates the integrity of microparticles and the possibility of long-term (up to 12 weeks) functioning of polymeric particles in vivo.
Subject(s)
Polymers/administration & dosage , Polymers/metabolism , Viscera/metabolism , Animals , Animals, Laboratory , Carbon Radioisotopes/administration & dosage , Carbon Radioisotopes/chemistry , Carbon Radioisotopes/metabolism , Female , Injections, Intravenous , Particle Size , Polymers/chemistry , Rats , Rats, Wistar , Tissue DistributionABSTRACT
An experimental dosage form of rubomycin is developed: the drug is incorporated in absorbable polymeric (polyhydroxybutyrate) matrix in the form of microparticles. Antitumor efficiency of this rubomycin dosage form was studied in laboratory mice with transplanted Ehrlich ascitic carcinoma. Rubomycin deposited in polymeric microparticles exhibited pronounced antitumor activity, inhibited the proliferative activity of Ehrlich ascitic carcinoma, and improved survival of mice with tumors. This dosage form of the drug can be used for local injections.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Daunorubicin/administration & dosage , Daunorubicin/therapeutic use , Microspheres , Absorption , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/mortality , Hydroxybutyrates , Mice , Mice, Inbred BALB C , PolyestersABSTRACT
Tissue reaction to implantation of polymeric microparticles from resorbable polymer (polyhydroxybutyrate) is characterized by slight inflammatory reaction and pronounced progressive macrophage infiltration with the presence of mono- and multinuclear foreign body giant cells resorbing the polymeric matrix. No fibrous capsules were formed around the polymeric microparticles; neither necrosis nor other adverse morphological changes and tissue transformation in response to implantation of the PHB microparticles were recorded. The results indicate good prospects of using polyhydroxybutyrate for the construction of long-acting dosage forms as microparticles for intramuscular injection.
