A biodegradable polymeric system for peptide–protein delivery assembled with porous microspheres and nanoparticles, using an adsorption/infiltration process

Abstract

Abstract:A biodegradable polymeric system is proposed for formulating peptides and proteins. The systems were assembled through the adsorption of biodegradable polymeric nanoparticles onto porous, biodegradable microspheres by an adsorption/infiltration process with the use of an immersion method. The peptide drug is not involved in the manufacturing of the nanoparticles or in obtaining the microspheres; thus, contact with the organic solvent, interfaces, and shear forces required for the process are prevented during drug loading. Leuprolide acetate was used as the model peptide, and poly(d,l-lactide-co-glycolide) (PLGA) was used as the biodegradable polymer. Leuprolide was adsorbed onto different amounts of PLGA nanoparticles (25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL) in a first stage; then, these were infiltrated into porous PLGA microspheres (100 mg) by dipping the structures into a microsphere suspension. In this way, the leuprolide was adsorbed onto both surfaces (ie, nanoparticles and microspheres). Scanning electron microscopy studies revealed the formation of a nanoparticle film on the porous microsphere surface that becomes more continuous as the amount of infiltrated nanoparticles increases. The adsorption efficiency and release rate are dependent on the amount of adsorbed nanoparticles. As expected, a greater adsorption efficiency (∼95%) and a slower release rate were seen (∼20% of released leuprolide in 12 hours) when a larger amount of nanoparticles was adsorbed (100 mg/mL of nanoparticles). Leuprolide acetate begins to be released immediately when there are no infiltrated nanoparticles, and 90% of the peptide is released in the first 12 hours. In contrast, the systems assembled in this study released less than 44% of the loaded drug during the same period of time. The observed release profiles denoted a Fickian diffusion that fit Higuchi's model (t 1/2 ). The manufacturing process presented here may be useful as a potential alternative for formulating injectable depots for sensitive hydrophilic drugs such as peptides and proteins, among others.

Peptide Functionalized Metallic Nanoconstructs: Synthesis, Structural Characterization, and Antimicrobial Evaluation

“…Correspondingly, these two peaks were identified in a thermogram of peptide ( 4b ) conjugate at ∼342.27 °C and ∼63.81 °C which suggested capping of peptide ( 4b ) on MPA-AuNPs (Figure S5A). In the case of MPA-AgNPs, a peak appeared at ∼161.31 °C and the peptide ( 4b ) conjugate showed two peaks at ∼311.18 °C and ∼161.01 °C, indicating the formation of peptide ( 4b ) capped MPA-AgNPs (Figure S6).…”

Nanonization and Deformable Behavior of Fattigated Peptide Drug in Mucoadhesive Buccal Films

“…DSC data could provide the homogeneity and crystallinity of the drug and other ingredients in the film. LEU exhibited intrinsic endothermic peaks at 87.7 °C and 154.1 °C, representing the glass transition temperature (Tg) and the melting point of intact LEU [ 39 ]. The thermograms of LOC, LON, and d-LON showed similar patterns, while d-LON exhibited an additional peak at 131.5 °C.…”

“…DSC data could provide the homogeneity and crystallinity of the drug and other ingredients in the film. LEU exhibited intrinsic endothermic peaks at 87.7 • C and 154.1 • C, representing the glass transition temperature (Tg) and the melting point of intact LEU [39]. The thermograms of LOC, LON, and d-LON showed similar patterns, while d-LON exhibited an additional peak at 131.5 • C. Endothermic drug peaks were also observed in all the physical mixtures; however, these peaks were not visible in the manufactured films containing LEU, LOC, and NPs, suggesting that these films are in an amorphous state.…”

Poly (lactic-co-glycolic acid) nanospheres allow for high l-asparaginase encapsulation yield and activity

“…This result can be explained by the porosity of nanospheres, which may have enabled the diffusion process allowing water to penetrate into the system forcing the protein to diffuse out to the dissolution medium [34]. However, as the ASNase molecules are not sufficiently small to pass through the polymer meshes, the observed initial release may have been the result of partial protein adsorption onto the surface of nanospheres rather than of its encapsulation within the polymeric mesh [35].…”