Specimens from a subset of 6 CF lung transplant recipients were selected for an

PLA and PHBHHxPEG NPs showed similar profiles of an initial burst release followed by a sustained discharge stage, which was a little bit faster than that from PHBHHx NPs. About 40% of the drug could be released within the first 24 hrs from PLA NPs and PHBHHx PEG NPs and only about 30% of RAP was released from PHBHHx NPs during the same period. At 75 hours, the percentage of retained order JNJ-7706621 drug in PHBHHx and PHBHHxPEG NPs were 42% and 25%, respectively, which demonstrated that the release of RAP from PHBHHxPEG NPs was faster than that from PHBHHx NPs. Interestingly, the release of RAP from PHA based NPs was more efficient than that from PLA NPs. Indeed, more than 95% of the drug could be released from the PHBHHx and PHBHHxPEG NPs after 10 days.<br><br> On the contrary, more than 30% RAP still remained in the PLA NPs even after 10 days, which indicated that this 30% supplier LDN193189 of drug was strongly encapsulated in the PLA NPs and could not be released. Such behavior might be explained by the relativly poor crystalline nature of PHBHHx and PHBHHxPEG materials, thus allowing RAP to diffuse from the loose particle core. These results thus indi cated that the PHBHHx and PHBHHxPEG nanoparti cles could efficiently and effectively extend the release profile of RAP and could be eventually used as con trolled delivery carriers for hydrophobic drugs. Cellular uptake of PHBHHx and PHBHHxPEG NPs Human prostate cancer cell line PC3 and a murine macro phage cell line RAW264. 7 were used to investigate the in vitro endocytosis of PHA based NPs.<br><br> Cells were treated with the rhodamine B solution, rhodamine B loaded PHBHHx NPs and PHBHHxPEG NPs in the same fluorescence intensity, respectively. After 3 hrs treatment, the intracellular fluorescence of the rhodamine B solution treated group was weak in both PC3 and RAW264. 7 cells, LY2228820 862507-23-1 which suggested that rhodamine B could not be easily absorbed by both these two cell lines, However, significant intracellular fluorescence signal could be de tected either by the fluorescence microscopy observation or by fluorescence intensity analysis in both PC3 and RAW264. 7 cells 3 hrs after the addition of rhodamine B loaded NPs. The internalized NPs were mainly accumulated in the cytoplasm and didnt reach the cell nucleus area, indicated by the weak fluorescence inten sity area inside the cells.<br><br> Moreover, the rhodamine B loaded PHBHHxPEG NPs treating group showed much stronger intracellular fluorescence intensity compared to the rhodamine B loaded PHBHHx NPs treating group, indicating that PHBHHxPEG NPs showed higher cell affin ity and easier cellular uptake. In vitro cytotoxicity evaluation of PHBHHx and PHBHHxPEG NPs The cytotoxic effect of PHBHHx and PHBHHxPEG NPs on PC3 was evaluated in vitro by MTT assay. Figure 4 shows relative proliferation percentage of PC3 incubated with different NPs at doses of 100, 500 and 1000 ug ml 1 for 24 h, respectively. PHBHHx and PHBHHxPEG NPs could be well tolerated at the concentration of 100 ug ml 1. However, decreased cell viability was observed in the groups treated with 1000 ug ml 1 and 500 ug ml 1 NPs, which resulted in 40% and 20% decrease of cell viability, respectively.