Omar A. Rahman*
Department of Pharmaceutical Chemistry, King Saud University, Saudi Arabia
Received: 02-Dec-2025, Manuscript No. dd- 25-182256; Editor assigned: 04-Dec-2025, PreQC No. dd-25-182256 (PQ); Reviewed: 15- Dec-2025, QC No. dd-25-182256; Revised: 20- Dec-2025, Manuscript No. dd-25-182256(R); Published: 30-Dec-2025, DOI: 10.4172/ dd.9.010.
Citation: Omar A. Rahman, Prodrug Design, Molecular Modeling and Drug Transport. RRJ Drug Deliv. 2025.9.010.
Copyright: © 2025 Omar A. Rahman, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Prodrug design is a strategic approach in pharmaceutical development in which an inactive or less active compound is chemically modified to improve its pharmacological properties. After administration, the prodrug is converted into the active drug within the body through enzymatic or chemical processes. This strategy is widely used to overcome limitations such as poor solubility, low permeability, rapid metabolism, and high toxicity. Molecular modeling has become an essential tool in prodrug design by enabling the prediction of molecular interactions and biological behavior. Drug transport, which involves the movement of drugs across biological membranes and within the body, is closely linked to both prodrug design and molecular modeling [1,2].
Discussion
Many promising drug candidates fail due to unfavorable absorption, distribution, metabolism, and excretion properties. Prodrug design addresses these challenges by temporarily modifying functional groups to optimize drug transport. For example, converting a polar drug into a more lipophilic prodrug can enhance membrane permeability and improve oral absorption. Once the prodrug crosses biological barriers, it is enzymatically cleaved to release the active drug at the target site [3,4].
Molecular modeling plays a critical role in rational prodrug development. Computational techniques such as molecular docking, quantitative structure–activity relationship modeling, and molecular dynamics simulations help predict how prodrugs interact with enzymes, transporters, and biological membranes. These methods reduce trial-and-error experimentation and accelerate the identification of suitable chemical modifications. By simulating drug–membrane and drug–transporter interactions, molecular modeling provides insight into the mechanisms of drug transport and guides the optimization of prodrug structures.
Drug transport involves both passive diffusion and active transport through membrane proteins. Many drugs are limited by poor permeability across the intestinal epithelium or restricted penetration into target tissues such as the brain. Prodrug strategies can exploit endogenous transport systems by attaching promoieties that are recognized by specific transporters. For example, amino acid or peptide-based prodrugs can utilize intestinal peptide transporters to enhance absorption. This targeted transport improves bioavailability and can reduce required doses [5].
The integration of molecular modeling with prodrug design also supports the prediction of metabolic pathways and conversion rates. This ensures that the prodrug is stable during circulation but efficiently activated at the desired site. However, challenges remain in accurately predicting complex biological systems, and experimental validation is still essential.
Conclusion
Prodrug design, supported by molecular modeling, represents a powerful strategy to improve drug transport and overall therapeutic performance. By rationally modifying drug structures and predicting their biological behavior, researchers can enhance absorption, targeting, and safety. Continued advances in computational methods and drug transport biology are expected to further strengthen prodrug development and contribute to more efficient and precise drug therapies.
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