Peptides and Proteins

The number of peptide and protein drugs is increasing steadily since they are becoming more and more assessable by using genetic engineering technology. However, their stability in body fluids, especially in the gastrointestinal tract, often is very low. In addition they often encounter difficulties in traversing membranes in the body. Peptides and proteins mostly bind rather well to nanoparticles, which can enable an improvement in the stability as well as in the transport across membranes and into specific cells.

The possibility of using nanoparticles to enable the oral delivery of the peptides insulin [103] and salmon calcitonin [365] and the transport of dalargin [30, 66] and kytorphin [354] was already shown and discussed in Sections 7.5.1 and 7.4, respectively.

The model protein bovine serum albumin (BSA) was incorporated into poly(lactic-co-glycolide) nanoparticles and their loading and release properties were investigated [389]. The release rate was fairly constant after an initial burst release and was enhanced by the incorporation of polox-amer 188, reaching approximately 100% with this preparation after 30 days. Other peptidic substances that were bound to nanoparticles include growth hormone releasing factor (hGRF) [77, 390], gangliosides [391], and granulocyte-colony stimulating factor (G-CSF) [392]. The stability of these factors was increased and their release could be modulated. Poly(isohexyl cyanoacrylate) nanoparticles were able to maintain rather constant plasma levels of this drug for over 24 h after subcutaneous administration to rats. In contrast, with the same dose of free GRF plasma levels about

7 times higher appeared after 2 min that deceased rapidly, and no GRF was detectable any more after 100 min [390]. Mice experiments were conducted with rhG-CSF bound to poly(isohexyl cyanoacrylate) nanoparticles by addition after

8 h after start of the polymerization. However, no increase in short-term effects was observable after intravenous injection of the nanoparticle preparation compared to free (rhG-CSF) [392].

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