The future of peptides in therapeutics will clearly depend on the route and the form of their delivery to the body. Among the possible strategies, micro- and nanoparticles represent exciting technologies able to improve the pharmacokinetic that fluorescently labelled bovine serum albumin does not interact chemically with the polymer matrix but that it is physically entrapped in the dense polymer matrix. SDS-PAGE analysis has indicated that the method of entrapping serum albumin in polylactic acid (PLA) microspheres, which involves an organic solvent, does not lead to a significant and irreversible aggregation of the protein [5]. On the other hand, low-molecular-weight amines and other nucleophilic substances tend to increase the degradation of polyesters [6]. Therefore, in certain situations, the peptide itself could induce decomposition of the polymer, leading to a decrease in the molecular weight. The difficulty in designing nanoparticle formulations combining a practical loading capacity with the absence of denaturing interactions between the peptide and the polymer is exemplified by the study carried out to incorporate growth hormone releasing factor (GRF) in polyalkyl cyanoacrylate nanoparticles [7]. In this study, the time of GRF incorporation in the polymerization medium seemed to be a critical factor. In fact, when the peptide was added a short time after the beginning of the polymerization, the loading in the polymer was high; probably because GRF was entrapped throughout the microparticle. However, a portion of the peptide, which probably acts as a polymerization initiator, became covalently bound to the polymer and was no longer active. When GRF was added later, it did not interact covalently but its adsorption to the nanoparticles was less efficient, probably because only the surface of the polymer was available for drug adsorption [7]. Although it has not been possible to discriminate between degraded GRF and GRF covalently bound to the polymer, it is obvious that the percentage of intact GRF is very low when this peptide is added soon after the beginning of polymerization. This suggests that part of the GRF probably plays a role as polymerization initiator and becomes covalently bound to the polymer. These observations are consistent with the anionic mechanism of polymerization of the cyanoacrylate monomers as proposed by Donnelly et al. [8]. Another major obstacle to the particulate formulation of peptides is the high water solubility of those molecules. Most of the typical processes for micro- or nanoencapsulation are based on the affinity of the compound for the lipophilic phase of an emulsion or for the polymer. As a result, drug loadings are usually less than 10%, especially with the solvent evaporation process. Therefore, more recently, a novel method has been proposed for the encapsulation of peptides into polylacticco-glycolic acid (PLAGA) microspheres. It is based on a modified solvent evaporation method using a double emulsion [9]. So prepared microspheres have been found to encapsulate more than 90% of fluorescently labelled bovine serum albumin [5]. A procedure has also been developed for peptide microencapsulation based on the phase separation Of poly(D,L-lactic acid-co-glycolic acid) induced by the addition of a silicone oil [10].
