Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYTPQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of approximately 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.
Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, has been used to improve bone and soft tissue defect healing in recent years. The aim of this study was to assess the effect of PRP on articular cartilage defects in a rabbit model. Forty-eight osteochondral defects created in the femoropatellar groove were (a) left untreated, (b) treated with autogenous PRP in a polylactic-glycolic acid (PLGA), or (c) with PLGA alone. Platelets were enriched 5.12-fold compared to normal blood in the PRP. After four and 12 weeks, the explanted tissue specimens were assessed by macroscopic examination, micro-computed tomography, and histological evaluation. Macroscopic examination, micro-computed tomography and histology of the newly formed cartilage and bone in the defect differ significantly between the PRPtreated and the untreated groups, and stimulatory effect of PRP on osteochondral formation was observed. In conclusion, PRP in PLGA improves osteochondral healing in a rabbit model.
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