Prediction of the loading/releasing Behavior of a pH-responsive Drug which has multiple pKa, through a Profound Combination of Theoretical Calculation, pKa, and DFT simulation: A novel Approach. | [Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23 • 2023]

Author(s):

1. Khalid Ahmed: L. E. J. Nanotechnology Centre, H. E. J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; Department of Pharmaceutical Sci, University of Kwa Zulu-Natal, Durban, South Africa

2. S. Najikhan Inamdar: Department of Pharmaceutical Sci, University of Kwa Zulu-Natal, Durban, South Africa

3. N. Rehman: Department of Pharmaceutical Sci, University of Kwa Zulu-Natal, Durban, South Africa

4. Adam A. Skelton: Department of Pharmaceutical Sci, University of Kwa Zulu-Natal, Durban, South Africa

Abstract:

Understanding and predicting chemical phenomena is the main goal of computational chemistry. A pH-responsive drughas been proposed to target drug delivery to a specific part of the human body. A smart hybrid system in which inorganic silica material was grafted by propylamine to produce a pHresponsive system is analyzed by DFT calculation. Alendronate (D), has been used as a model drug and loaded into the hybrid nanoparticles. The novel combination of theoretical calculation, pKa, and DFT result showed that pH-responsive drug loading was carried out in acidic pH and released in basic pH. The results showed evident pH dependency, showing its pH-responsive properties. Herein we present a novel combination of theoretical calculation, classical pKa/pH theory with quantum mechanical calculations to predict the extent of interaction between acid/base dependent species at the full range of pH conditions. The model relies on the possible combinations of protonation states of the surface (S), drug (D), and functional group (F) in the neutral (0) and deprotonated (-1) and protonated (+1) states. Where alendronate has 5 possible states because alendronate has four different types of Pka, whose relative probabilities depend on their pKa at the desired pH. Therefore without functional group, there will be 10 combinations identified as follows S0D1-1, S0D1-2,S0D1-3, S0D-4, S0D-5, S-1D1-1, S-1D1-2,S-1D1-3, S-1D-4and S-1D-5 where in the presence of functional group it will be twenty combinations mentioned as follows S0F0D1-1, S0F0D1-2,S0F0D1-3, S0F0D-4, S0F0D-5, S-1F0D1-1, S-1F0D1-2,S-1F0D1-3, S-1F0D-4, S-1F0D-5, S0F+D1-1, S0F+D1-2,S0F+D1-3, S0F+D-4, S0F+D-5, S-1F+D1-1, S- 1F+D1-2,S-1F+D1-3, S-1F+D-4, and S-1F+D-5. Periodic DFT calculations were used to calculate a pKadependent interaction energy (Eint pH). Eint pH was negative at the acidic environment (pH 2–5) where the drug is loaded and positive at a slightly basic pH of 7–8 where it is released, in accordance with the experimental data reported in the literature.

Page(s): 321-321

DOI: DOI not available

Published: Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023

Keywords:

Alendronate , DFT , MSN , delivery and novel combination

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