In vitro and transdermal penetration of PHBV micro/nanoparticles.

The purpose of this study was to develop micro and nano sized drug carriers from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and study the cell and skin penetration of these particles. PHBV micro/nanospheres were prepared by o/w emulsion method and were stained with a fluorescent dye, Nile Red. The particles were fractionated by centrifugation to produce different sized populations. Topography was studied by SEM and average particle size and its distribution were determined with particle sizer. Cell viability assay (MTT) was carried out using L929 fibroblastic cell line, and particle penetration into the cells were studied. Transdermal permeation of PHBV micro/nanospheres and tissue reaction were studied using a BALB/c mouse model. Skin response was evaluated histologically and amount of PHBV in skin was determined by gas chromatography-mass spectrometry. The average diameters of the PHBV micro/nanosphere batches were found to be 1.9 µm, 426 and 166 nm. Polydispersity indices showed that the size distribution of micro sized particles was broader than the smaller ones. In vitro studies showed that the cells had a normal growth trend. MTT showed no signs of particle toxicity. The 426 and 166 nm sized PHBV spheres were seen to penetrate the cell membrane. The histological sections revealed no adverse effects. In view of this data nano and micro sized PHBV particles appeared to have potential to serve as topical and transdermal drug delivery carriers for use on aged or damaged skin or in cases of skin diseases such as psoriasis, and may even be used in gene transfer to cells.

Study of the efficiency of doxorubicin deposited in microparticles from resorbable Bioplastotane™ on laboratory animals with Ehrlich's solid carcinoma.

Antitumor efficiency of an experimental form of an experimental form of anthracyclin antibiotic (doxorubicin), resorbable microparticles from Bioplastotane(TM), was studied on laboratory mice with transplanted Ehrlich's solid carcinoma. Use of the experimental form of the cytostatic in polymeric microparticles from resorbable Bioplastotane(TM)in animals with solid tumor led to inhibition of the cancerous process, comparable to that in response to intravenous free doxorubicin, but without negative effects on the blood system.

Distribution and resorption of polymeric microparticles in visceral organs of laboratory animals after intravenous injection.

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.

Evaluation of antitumor activity of rubomycin deposited in absorbable polymeric microparticles.

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.

Tissue reaction to intramuscular injection of resorbable polymer microparticles.

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.