Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) microspheres for controlled release of buprofezin.

Extensive application of pesticides has caused a lot of environmental pollution and health problems, prompting the development of highly efficient and lowly toxic pesticide formulations. Here, buprofezin (BPF)-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-HH)) microspheres were prepared by O/W emulsion/solvent evaporation method. Under optimal conditions (P(HB-HH) 7.07% (w/v) and PVA 1.84% (w/v)), the spherical and monodispersed microspheres were obtained. The average particle size, pesticide loading (PL), and encapsulation efficiency (EE) of the optimized microspheres were 1.2 µm, 15.68%, and 78%, respectively. Release of 80% BPF from the microspheres in pH 5 (192 h) was faster than that in pH 7 (228 h) and 8 (204 h). Moreover, kinetic analysis indicated that BPF release behaved in a non-Fickian diffusion manner (0.43 < n < 0.85) and the release mechanism was the combined effects of pesticide diffusion and hydrolysis of polymer. The bioassay and toxicity results showed that encapsulation of BPF could exhibit high efficacy on the target organism and low toxicity to the non-target organism. Therefore, these results demonstrated that BPF-loaded P(HB-HH) microspheres with good stability were prepared successfully, and they could be further explored for constructing other highly efficient and lowly toxic pesticide formulations.

Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay.

CONTEXT: Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] were prepared by the W1/O/W2 solvent extraction/evaporation method for applications in cancer treatment. However, the biodistribution, pharmacokinetics, and targeting of the nanoparticles (NPs) have not yet been studied. OBJECTIVE: The biodistribution, pharmacokinetics, and targeting of DOX/FA-PEG-P(HB-HO) NPs were evaluated in female BALB/c nude mice bearing HeLa tumors. MATERIALS AND METHODS: Three DOX formulations were injected into the tail vein of the mice at a dosage of 5 mg/kg. At each time point, blood and various tissues were collected. All samples were then processed and analyzed by a validated high performance liquid chromatographic (HPLC) method. RESULTS: The t1/2 values of DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were 2.7- and 3.5-times higher than that of free DOX. No significant difference (p > 0.05) was found in Cmax between the NPs and free DOX. The Tmax values of the two NPs were prolonged from 0.25 to 1 h. The AUC0-t values were 1.55- and 3.05-folds higher than that of free DOX, and MRT increased to 15.99 h for DOX/P(HB-HO) NPs and 25.14 h for DOX/FA-PEG-P(HB-HO) NPs. For DOX/FA-PEG-P(HB-HO) NPs, the DOX content in the tumors were 10.81- and 3.33-times higher than those for free DOX and DOX/P(HB-HO) NPs at 48 h, respectively. DISCUSSION AND CONCLUSIONS: DOX/FA-PEG-P(HB-HO) NPs displayed reduced cardiac toxicity and improved bioavailability. Moreover, the NPs exhibited a significant extent of DOX accumulation in the tumors, thus suggesting that folate-targeted NPs could effectively transport into HeLa tumors with satisfying targeting.

Preparation and characterization of novel microparticles based on poly(3-hydroxybutyrate-co-3-hydroxyoctanoate).

In this study, a novel poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) (P(HB-HO)) microparticle with an encapsulated antibiotic (azithromycin, AZI) was prepared by the electrospinning method. The resulting microparticles were evaluated for surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug-release and degradation. The in vitro cytotoxicity and in vivo pharmacokinetics were also studied. The sizes of microparticles showed a narrow monodisperse size distribution approximately from 3 to 30 µm. In vitro release experiments exhibited sustained release behavior. The results of in vitro degradation tests demonstrated that the mass loss of the P(HB-HO) microparticles was 9.6% and the morphology varied greatly within 24 weeks. P(HB-HO) showed no cytotoxicity to fibroblast when incubated with blank P(HB-HO) microparticles during the tests. The in vivo pharmacokinetic study demonstrated that the microparticles exhibited longer circulation properties than free AZI. It is suggested that novel AZI-loaded P(HB-HO) microparticles can be utilized as a biodegradable and biocompatible drug delivery system.

Folate-mediated poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting drug delivery.

A novel targeting drug delivery system (TDDS) has been developed. Such a TDDS was prepared by W(1)/O/W(2) solvent extraction/evaporation method, adopting poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] as the drug carrier, folic acid (FA) as the targeting ligand, and doxorubicin (DOX) as the model anticancer drug. The average size, drug loading capacity and encapsulation efficiency of the prepared DOX-loaded, folate-mediated P(HB-HO) nanoparticles (DOX/FA-PEG-P(HB-HO) NPs) were found to be around 240 nm, 29.6% and 83.5%. The in vitro release profile displayed that nearly 50% DOX was released in the first 5 days. The intracellular uptake tests of the nanoparticles (NPs) in vitro showed that the DOX/FA-PEG-P(HB-HO) NPs were more efficiently taken up by HeLa cells compared to non-folate-mediated P(HB-HO) NPs. In addition, DOX/FA-PEG-P(HB-HO) NPs (IC(50)=0.87 microM) showed greater cytotoxicity to HeLa cells than other treated groups. In vivo anti-tumor activity of the DOX/FA-PEG-P(HB-HO) NPs showed a much better therapeutic efficacy in inhibiting tumor growth, and the final mean tumor volume was 178.91+/-17.43 mm(3), significantly smaller than normal saline control group (542.58+/-45.19 mm(3)). All these results have illustrated that our techniques for the preparing of DOX/FA-PEG-P(HB-HO) NPs developed in present work are feasible and these NPs are effective in selective delivery of anticancer drug to the folate receptor-overexpressed cancer cells. The new TDDS may be a competent candidate in application in targeting treatment of cancers.