In recent years, the use of drug delivery systems based on polymeric nanoparticles (NPs) has generated innovative strategies for several diseases1,2. Polylactic acid (PLA) is one of the most commonly used polymers for the synthesis of NPs3, PLA-NPs conjugated with hydrophilic molecules like polyethylene glycol (PEG) presents improved blood circulation, biocompatibility, and less cytotoxicity4.
The current high prevalence of cardiovascular diseases (CVD) and the vast application of PEGylated NPs propose an excellent opportunity to develop novel therapeutic approaches for CVD.
In this work, we employed a combination of Molecular Dynamic simulations and Blind Docking techniques to understanding the structural and physiochemical properties that establish the association of cilostazol and adenosine 5'-monophosphate (AMP), both antiaggregant compounds, with PLA-NPs and to characterize the host-guest chemistry of complexes as novel nanosystem for CVD.
The results showed that cilostazol structure allows a better alignment with the PLA unit than AMP and presented the highest affinity to PLA core, which was consistent with logP values. However, Steered Molecular Dynamics showed a similar behavior of drug release.
The structural characterization in silico of polymers-drugs provides a comprehensive understanding of the factors that contribute to NP formation and drug loading of nanocarriers based on polymeric NPs. This approach represents an innovative strategy to evaluate the drug encapsulation of several antiplatelet drugs into PLA-NPs.
References
- Bae, Y., Adv. Drug Deliv. Rev., 61, 768, 2009.
- Avgoustakis, K., Curr. Drug Deliv., 1, 321, 2004.
- Xiao, R. Z., Int. J. Nanomedicine, 5, 1057, 2010.
- Gref, R., Protein Delivery, 167, 2002.
Acknowledgements: CONICYT-PCHA/Doctorado Nacional/2014-21140225. CV acknowledges the financial support of FONDECYT
Regular #1161438. UNAB Regular, DI-695-15/R.
