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Code : 19300-2148      Created Date : Tuesday, October 22, 2019   Update Date : Tuesday, October 22, 2019    Visit : 714

English Lecture Series: Dr. Mehrnoosh Shirangi

First lecture of winter semester scientific english lecture series (2019) was held by Dr. Mehrnoosh Shirangi on Oct 21, 2019 in the title of Assessment and Identification of Acylated Peptides from Poly (lactic-co-glycolic acid) (PLGA) Microspheres by LC-MS-MS

Summary of the talk:

In recent years, there has been an increasing interest in peptide and protein delivery systems in order to facilitate their controlled delivery and sustain therapeutic efficacy. Microspheres of biodegradable Poly (D,L-lactide-co-glycolide) (PLGA) has been extensively used for prolonged release of bioactive peptides. However, one of the issues in peptide delivery using PLGA formulations is the formation of peptide adducts as a result of acylation with lactic and glycolic acids.


In our first study, the acylation adducts of octreotide acetate released from PLGA microspheres were identified and compared with the same peptide that was released from poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) and from  poly(lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) microspheres. In our second study, goserelin peptide, which lacks known sites of acylation like the N terminus and primary NH of Lysine, was assessed for acylation in PLGA microspheres.


Peptide loaded microspheres were prepared by double emulsion solvent evaporation technique (W1/O/W2). Microspheres were characterized (size, morphology) and the in vitro release study was performed in PBS buffer at 37˚C. At predetermined time points, the suspensions were centrifuged and the concentration of peptide was measured in each supernatant.


In order to analyze the molecular weight of released (acylated) peptide, LC-MS was performed with electrospray ionization in positive ion mode, and an ion-trap mass spectrometer. To scrutinize the structural information and localize the actual modification site, LC-MS-MS was performed on the acylated adducts.


Our data demonstrate that less acylated octreotide adducts were formed in PLHMGA and PLGHMGA microspheres than in PLGA. Moreover, besides the N terminus and primary NH of lysine in octreotide, we have found that the primary OH of threonine in the end group of octreotide was also subjected to acylation. Surprisingly, in goserelin, arginine was also acylated. We propose that acylation in goserelin follows by ring closure to reach a stable cyclic form.






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