Mechanistic Studies on the Degradation and Protein Release Characteristics of Poly(lactic-co-glycolic-co-hydroxymethylglycolic acid) Nanospheres

Abstract

The purpose of this study was to gain mechanistic insights into the effect of different formulation parameters on the degradation and release behavior of protein-loaded nanoparticulate carrier systems based on an aliphatic polyester with pendant hydroxyl groups, poly(lactic-co-glycolic-hydroxymethyl glycolic acid) (pLGHMGA). Bovine serum albumin (BSA) was used as a model protein. BSA-loaded pLGHMGA nanospheres of 400-700 nm were prepared using a solvent evaporation method using pLGHMGA of different molecular weights and different compositions. Also, the concentration of pLGHMGA in the organic phase was varied. The nanospheres showed a continuous mass loss accompanied by continuous decrease in number average molecular weight, which indicates that the degradation of the nanospheres is by bulk degradation with a rapid release of water-soluble low molecular weight fragments. On the basis of NMR analysis, it is concluded that intramolecular transesterification precedes extensive hydrolysis of the polymer and degradation of the nanospheres. BSA-loaded freeze-dried nanospheres showed a significant burst release of 40-50% of the BSA loading. In contrast, nonfreeze-dried samples showed a small burst of around 10-20%, indicating that freeze-drying induced pore formation. Nonlyophilized nanospheres prepared from pLGHMGA with 64/18/18 lactic/glycolic/hydroxymethylglycolic acid (L/G/HMG) ratio showed a relatively fast release of BSA for the next 30 days. Nanospheres prepared from a more hydrophobic pLGHMGA (74/13/13, L/G/HMG) showed a two-phase release. Circular dichroism analysis showed that the secondary structure of the released protein was preserved. This study shows a correlation between release behavior and particle erosion rate, which can be modulated by the copolymer composition.

Basics and Recent Advances in Peptide and Protein Drug Delivery

“…The release of protein from an aliphatic polyester-based nanoparticle system was caused by bulk degradation of the nanoparticle. Moreover, intramolecular transesterification was followed by hydrolysis of the polymers, which caused the degradation [197]. Further, lyophilizing NPs led to a higher burst release of protein (40–50%) compared with nonlyophilized NPs (10–20%).…”

Preparation, Characterization, In Vitro Release and Degradation of Cathelicidin-BF-30-PLGA Microspheres

“…Furthermore, Figure 7 shows that the far-UV CD spectrum of the peptide in the release medium of the 1 st day and of the later period of the release process, the 12 th and 13 th days, matching that of the native peptide. This demonstrates that the released BF-30 retains its α-helical secondary structure [30], indicating that the structure of BF-30 has not changed during the release process.…”

GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy

“…According to previous literature reports, 39,40 MDA-MB-231 and MCF-7 cells express 2×10 5 and 1×10 4 EGFR per cell and exhibit positive and negative expression of CD44, respectively. MDA-MB-231 cells were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) with 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in 5% CO 2 atmosphere.…”

“…43 Briefly, 250 μL of the polymer aqueous solution (5 mg/mL) was diluted with 250 μL of phosphate-buffered saline (PBS) 8.0 (0.1 M). Disulfide linkages were reduced by the addition of 500 μL of freshly prepared 2% aqueous solution of NaBH 4 . Following 1 hour stirring at 40°C, the excess amount of NaBH 4 was discarded by the addition of 0.3 mL of 1 N HCl and the mixture was completed by 1.2 mL of PBS 8.0.…”