TY - JOUR
T1 - Prodrug Therapies for Infectious and Neurodegenerative Diseases
AU - Markovic, Milica
AU - Deodhar, Suyash
AU - Machhi, Jatin
AU - Yeapuri, Pravin
AU - Saleh, Maamoon
AU - Edagwa, Benson J.
AU - Mosley, Rodney Lee
AU - Gendelman, Howard E.
N1 - Funding Information:
Funding: National Institutes of Health grants R01 AI145342, R01 Al158160, T32 NS105594, R01 NS36126, P01 NS31492; R01NS034239; P01 MH64570; P30 MH062261; and from the University of Nebraska Foundation (the Carol Swarts, M.D. Emerging Neuroscience Research Laboratory; the Margaret R. Larson Professorship; the Robert Eisenberg, the Frances and Louie Blumkin and the Harriet Singer Endowments).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3
Y1 - 2022/3
N2 - Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.
AB - Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.
KW - Drug derivatization
KW - HIV-associated neurocognitive disorders (HAND)
KW - Hepatitis
KW - Human immunodeficiency virus (HIV)
KW - Infectious diseases
KW - Neurodegenerative disorders
KW - Prodrugs
KW - SARS-CoV-2
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U2 - 10.3390/pharmaceutics14030518
DO - 10.3390/pharmaceutics14030518
M3 - Review article
C2 - 35335894
AN - SCOPUS:85125663280
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 3
M1 - 518
ER -