Novel Insights Into Appropriate Encapsulation Methods for Bioactive Compounds Into Polymers: A Study With Peptides and HDAC Inhibitors

Abstract

The use of different nanoparticles (NPs) for successful encapsulation of bioactive substances is discussed. The inclusion efficiency into liposomes, acetalated dextran (Ac-Dex), and variants of poly[(lactic acid)-co-(glycolic acid)] (PLGA) NPs is analyzed after chemical degradation. Efficient inclusion of SIRT1 inhibitor Ex527 in liposomes, Ac-Dex- and PLGA-NPs is observed for all procedures used. Activity of Ex527 is demonstrated by monitoring the acetylation status of SIRT1-target p53. In contrast, small peptides are only incorporated into acid-terminated PLGA-NPs and marginally into Ac-Dex-NPs. The yield depends on peptide sequence and terminal modifications. Activity is exemplified for angiotensin II using the dynamic mass redistribution technology.

A robust microparticle platform for a STING-targeted adjuvant that enhances both humoral and cellular immunity during vaccination

“…cGAMP could not be reliably encapsulated within PLGA MPs using the double emulsion procedure. This is consistent with previous studies that attempted to encapsulate other hydrophilic cargo within PLGA MPs using similar emulsion methods [63, 64]. Compared to other reported CDN delivery vehicles (polymeric hydrogel particles (47%) [42] or liposomes (2 to 35%) [41, 43–45]), electrospray was able to achieve a significantly superior CDN EE (90%).…”

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

“…Deuterated and non-deuterated lipid mediator standards for UPLC-MS-MS quantification were purchased from Cayman Chemical/Biomol (Germany). For further materials, see specific experimental section.4.2 Acdex-rhodamine B synthesisRhodamine B was coupled to Acdex (Mw 9 to 11 kDa, Sigma Aldrich) according to an adapted procedure[43]: 1 g Acdex (6.17 mmol anhydroglucose unit, DS acyclic acteal = 0.56, DS cyclic acetal = 2.14) and 13 mg rhodamine B isothiocyanate were dissolved in 15 mL anhydrous pyridine and heated to 80 °C for 72 h under argon. The reaction mixture was precipitated in 150 mL distilled water, and centrifuged; the pellet was lyophilized.…”

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

“…Rhodamine B was coupled to Acdex (Mw 9 to 11 kDa, Sigma Aldrich) according to an adapted procedure [43]: 1 g Acdex (6.17 mmol anhydroglucose unit, DS acyclic acteal = 0.56, DS cyclic acetal = 2.14) and 13 mg rhodamine B isothiocyanate were dissolved in 15 mL anhydrous pyridine and heated to 80 °C for 72 h under argon. The reaction mixture was precipitated in 150 mL distilled water, and centrifuged; the pellet was lyophilized.…”