Pheroid technology for the topical delivery of insulin growth factor 1 (IGF-1), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF)

Abstract

The biotechnological era is here and many peptides and proteins are being used as part of drug therapy. They are, however, not very stable and do not have the physicochemical properties that allow for oral or topical delivery, and currently the most suitable method of delivery is via very invasive subcutaneous or intravenous injection. Growth factors are the peptides this study was aimed at exploring ; in this case insulin-like growth factor 1 (IGF-1), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF). These growth factors in particular have a stimulating effect on hair growth and strong hair shaft production. In addition, KGF has a protective effect on cells against radiation-induced cytotoxicity. The aim of this study was to investigate the in vitro topical diffusion of the growth factors IGF- 1, KGF and VEGF with the assistance of Pheroid™ drug delivery technology. In general, peptides such as growth factors are presumed to be unsuitable for topical delivery. It was, however, thought to be sensible to explore the drug delivery with Pheroid™ technology after significant success was achieved with a variety of drugs in previous studies. In order to prevent growth factor degradation by the skin, bestatin, a potent selective aminopeptidase inhibitor was utilized after its proven success in previous studies. The diffusion studies were done with the use of vertical Franz diffusion cells and human female abdominal skin and were conducted over a period of 6 hours. A solution of each of the growth factors, IGF-1, KGF and VEGF, in the Pheroid™ delivery system was used as the donor solution and placed in the donor compartment of 6 diffusion cells for each growth factor. As a control, a solution of each of the growth factors, IGF-1, KGF and VEGF in phosphate buffered solution (PBS) was placed in the donor compartment of 6 diffusion cells . PBS (pH 7.4) was also utilized as the receptor solution in all of the diffusion studies. Samples were taken after the completion of the 6 hours diffusion study and analysed with the help of ELISA immunoassays. ELISA immunoassays showed that the Pheroid™ drug delivery system was successful in the improvement of the delivery and stability of both IGF-1 and VEGF. In the case of IGF-1 in Pheroid™, an improvement of 6% in diffusion and an increase in instability were observed when compared to the data of PBS. In the case of VEGF the Pheroid™ drug delivery system showed a 31% improvement in diffusion; it does not, however, have a significant effect on the stability thereof when compared with the VEGF in PBS. The adjusted Pheroid™ drug delivery system values for the epidermis, showed a decrease of 43% for IGF-1, a 97% decrease for KGF and a 18% decrease in the tape stripping concentration values obtained

in comparison with PBS. In the dermis case, the adjusted Pheroid™ drug delivery system showed a decrease of 44% for IGF-1, a decrease of 97% for KGF and a decrease of 19% for VEGF in the dermis concentration values obtained in comparison with PBS. It was, however, found that the Pheroid™ drug delivery system does not show an improvement in the delivery or the stability of KGF and is to the contrary detrimental to it, with a 97% decrease in diffusion and an approximate 51% degradation of KGF at both 25 and 37°C in comparison to the KGF in PBS. Therefore, the suitability of the Pheroid™ drug delivery system needs to be ascertained in order to ensure the delivery and stability of the active entrapped within the Pheroid™ drug delivery system. The Pheroid™ drug delivery system therefore improves the transdermal delivery as well as the stability of IGF-1. It also improves the transdermal delivery of VEGF considerably. This particular Pheroid™ form is, however, not suited for the delivery or maintained stability of KGF, since both the transdermal delivery and stability of KGF have been impaired in this study. By ascertaining whether the Pheroid™ drug delivery system is able to facilitate the topical delivery of the growth factors, the possible use thereof in the treatment of alopecia in the future can be determined.