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Abstract

The use of PLA and PLGA for drug delivery needs substantially more circumspection. As, according to FDA standards. the potential hazards of peptide acylation products need to be assessed, our findings may have significant implications for products already on the market. Techniques to minimize the acylation reaction are suggested.

Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

“…This presence of multiple peaks on the chromatogram with 1 or 2 glycolic acid units each also revealed that octreotide has multiple acylation sites (23). Nucleophilic functional groups such as the primary amino groups present in the N-terminus and lysine residue have been shown to be the major targets for peptide acylation (17, 19, 30). The individual peaks, octreotide and octreotide degradated products in HPLC chromatogram were identified through LC-MS based on the retention times.…”

“…Porous microspheres allow for rapid release of acidic PLGA oligomers, which typically raises the microclimate pH within eroding microspheres (32). Since acylation has been shown to be accelerated by high concentrations of oligomers in solution, as well as by acidic conditions (19, 20), more porous microspheres were expected to slow down and suppress the acylation of octreotide. In addition, acylation in microspheres containing water-soluble divalent cationic salts might be prevented by reducing sorption of octreotide to PLGA (26).…”

“…The formation of acylated peptide impurities poses another potential obstacle to the successful delivery of bioactive substances from PLGA, as peptide (or potentially protein) acylation could have detrimental effects, such as loss of activity, immunogenicity and toxicity (18, 19). Peptide acylation has been shown to be affected by polymer composition and solution pH (20, 21).…”

Degradation of vitamin D3 in a stressed formulation: The identification of esters of vitamin D3 formed by a transesterification with triglycerides

“…The formation of ethyl-2-mercapto-acetate from residual ethanol present in an excipient (sodium starch glycolate) and compounds related to a thermal stabilizer present in PVC packaging material has been reported recently [35]. The acylation of peptides by lactic acid and glycolic acid inside degrading microspheres of poly(lactic acid) and poly(lacticco-glycolic acid) has also been observed [36]. Methylparaben (methyl p-hydroxybenzoate), used widely as an anti-microbial preservative, has been shown to undergo transesterification reactions with aldoses and alditols which are common excipients in pharmaceuticals [37].…”

Development and Characterization of Electrospun Poly(2‐hydroxy ethyl methacrylate) for Tissue Engineering Applications

“…4 Among these, p(HEMA) is one type of poly(α-hydroxy ethyl methacrylate) approved by U.S. Food and Drug Administration for clinical use. 5 It has proved to be a good candidate in the biomaterial field because of its high biocompatibility, 6, 7 nontoxicity, 8 better oxygen permeability, 9 and good transmission and absorption characteristics. 10 It has remarkable tolerance to entrapped cells and exhibits good chemical and hydrolyte stability.…”