Kinetics of Drug Release from Clay Using Enhanced Sampling Methods

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Dec 23

PMID 36559081

Authors

Ana Borrego-Sanchez

Jayashrita Debnath

Michele Parrinello

Affiliations

Soon will be listed here.

Abstract

A key step in the development of a new drug, is the design of drug-excipient complexes that lead to optimal drug release kinetics. Computational chemistry and specifically enhanced sampling molecular dynamics methods can play a key role in this context, by minimizing the need for expensive experiments, and reducing cost and time. Here we show that recent advances in enhanced sampling methodologies can be brought to fruition in this area. We demonstrate the potential of these methodologies by simulating the drug release kinetics of the complex praziquantel-montmorillonite in water. Praziquantel finds promising applications in the treatment of schistosomiasis, but its biopharmaceutical profile needs to be improved, and a cheap material such as the montmorillonite clay would be a very convenient excipient. We simulate the drug release both from surface and interlayer space, and find that the diffusion of the praziquantel inside the interlayer space is the process that limits the rate of drug release.

Citing Articles

The New Attempt at Modeling of the Three-Dimensional Geometry of the Epidermal Skin Layer and the Diffusion Processes of Nanomolecular Drug Carriers in Such Structures.

Blaszczyk M, Sek J Molecules. 2023; 28(1).

PMID: 36615399 PMC: 9822492. DOI: 10.3390/molecules28010205.

References

Rodrigues L, Figueiras A, Veiga F, de Freitas R, Nunes L, da Silva Filho E . The systems containing clays and clay minerals from modified drug release: a review. Colloids Surf B Biointerfaces. 2012; 103:642-51. DOI: 10.1016/j.colsurfb.2012.10.068. View

Meirelles L, Raffin F . Clay and Polymer-Based Composites Applied to Drug Release: A Scientific and Technological Prospection. J Pharm Pharm Sci. 2017; 20(0):115-134. DOI: 10.18433/J3R617. View

Dong J, Cheng Z, Tan S, Zhu Q . Clay nanoparticles as pharmaceutical carriers in drug delivery systems. Expert Opin Drug Deliv. 2020; 18(6):695-714. DOI: 10.1080/17425247.2021.1862792. View

Cioli D, Pica-Mattoccia L . Praziquantel. Parasitol Res. 2003; 90 Supp 1:S3-9. DOI: 10.1007/s00436-002-0751-z. View

Grubmuller . Predicting slow structural transitions in macromolecular systems: Conformational flooding. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1995; 52(3):2893-2906. DOI: 10.1103/physreve.52.2893. View

Babin V, Roland C, Sagui C . Adaptively biased molecular dynamics for free energy calculations. J Chem Phys. 2008; 128(13):134101. DOI: 10.1063/1.2844595. View

Boniatti J, Januskaite P, da Fonseca L, Vicosa A, Amendoeira F, Tuleu C . Direct Powder Extrusion 3D Printing of Praziquantel to Overcome Neglected Disease Formulation Challenges in Paediatric Populations. Pharmaceutics. 2021; 13(8). PMC: 8398999. DOI: 10.3390/pharmaceutics13081114. View

Colley D, Bustinduy A, Evan Secor W, King C . Human schistosomiasis. Lancet. 2014; 383(9936):2253-64. PMC: 4672382. DOI: 10.1016/S0140-6736(13)61949-2. View

Debnath J, Parrinello M . Gaussian Mixture-Based Enhanced Sampling for Statics and Dynamics. J Phys Chem Lett. 2020; 11(13):5076-5080. DOI: 10.1021/acs.jpclett.0c01125. View

10.

Chitsulo L, Engels D, Montresor A, Savioli L . The global status of schistosomiasis and its control. Acta Trop. 2000; 77(1):41-51. PMC: 5633072. DOI: 10.1016/s0001-706x(00)00122-4. View

11.

Andrews P . Praziquantel: mechanisms of anti-schistosomal activity. Pharmacol Ther. 1985; 29(1):129-56. DOI: 10.1016/0163-7258(85)90020-8. View

12.

Lindenberg M, Kopp S, Dressman J . Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm. 2004; 58(2):265-78. DOI: 10.1016/j.ejpb.2004.03.001. View

13.

Heinz H, Lin T, Mishra R, Emami F . Thermodynamically consistent force fields for the assembly of inorganic, organic, and biological nanostructures: the INTERFACE force field. Langmuir. 2013; 29(6):1754-65. DOI: 10.1021/la3038846. View

14.

Maragakis P, van der Vaart A, Karplus M . Gaussian-mixture umbrella sampling. J Phys Chem B. 2009; 113(14):4664-73. PMC: 2806548. DOI: 10.1021/jp808381s. View

15.

de Jesus M, de Matos Alves Pinto L, Fraceto L, Magalhaes L, Zanotti-Magalhaes E, de Paula E . Improvement of the oral praziquantel anthelmintic effect by cyclodextrin complexation. J Drug Target. 2009; 18(1):21-6. DOI: 10.3109/10611860903131677. View

16.

Invernizzi M, Parrinello M . Rethinking Metadynamics: From Bias Potentials to Probability Distributions. J Phys Chem Lett. 2020; 11(7):2731-2736. DOI: 10.1021/acs.jpclett.0c00497. View

17.

Wang W, Wang L, Liang Y . Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res. 2012; 111(5):1871-7. DOI: 10.1007/s00436-012-3151-z. View

18.

Ansari N, Rizzi V, Parrinello M . Water regulates the residence time of Benzamidine in Trypsin. Nat Commun. 2022; 13(1):5438. PMC: 9481606. DOI: 10.1038/s41467-022-33104-3. View

19.

Ray D, Ansari N, Rizzi V, Invernizzi M, Parrinello M . Rare Event Kinetics from Adaptive Bias Enhanced Sampling. J Chem Theory Comput. 2022; 18(11):6500-6509. DOI: 10.1021/acs.jctc.2c00806. View

20.

Zhang J, Manias E, Wilkie C . Polymerically modified layered silicates: an effective route to nanocomposites. J Nanosci Nanotechnol. 2008; 8(4):1597-615. View