Amino Acid Derived Prodrugs: An Approach to Improve the Bioavailability of Clinically Approved Drugs

Abstract

: Amino acids derived prodrugs emerged as an attractive approach to improve oral delivery of drugs with low solubility and permeability. Conjugation of amino acids with parent drug molecules resulted in several-fold increases in water solubility. Acceptability of the amino acids derived prodrug approach increases day by day to fulfill the different characteristics needed to get the desired pharmacological or therapeutic activity. Due to the significant structural diversity of amino acid, various amino acids can be employed as a carrier to provide desirable Pharmacokinetic-Pharmacodynamic (PK-PD) characteristics. The present review focused on using amino acids as a carrier moiety to improve approved drugs' bioavailability. Attempts have been made to cover amino acid conjugated clinically available drugs.

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

“…Many years later, Bos et al [ 179 ] identified 3-methylheptane, octane, and acetaldehyde in the EBC of patients with ARDS. Singh et al [ 180 ] found associations with N-acetyl glycoproteins, acetoacetate, lactate, creatinine, histidine, formate, and branched-chain amino acids, and Stringer et al [ 181 ] confirmed the association with ARDS and phosphatidyl serine, total lipids, and total choline. Since the advent of the COVID-19 pandemic, a comparison of metabolomic signatures between patients with H1N1 and patients with COVID-19 with ARDS was performed.…”

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability

“…As a natural substance, amino acids (AAs) are accessible and inexpensive and have high safety, making them suitable for use as the ideal promoiety of prodrugs. 28 AAs can also enhance the water solubility of the insoluble compounds. Furthermore, AA prodrugs can cross the biological membrane via transporters expressed in the intestine, such as organic anion-transporting polypeptide 2B1 (OATP2B1) and oligopeptide transporter 1 (PEPT1).…”

“…For phenol drugs, the carbamate linkage is the preferred bioreversible linkage because of various advantages such as , (1) the superior chemical and enzyme stability of the carbamate bond, (2) suitability for protecting phenols against first-pass metabolism after oral administration, and (3) utility as the substrates of specific enzymes in plasma, which could catalyze the bioconversion of prodrugs. As a natural substance, amino acids (AAs) are accessible and inexpensive and have high safety, making them suitable for use as the ideal promoiety of prodrugs . AAs can also enhance the water solubility of the insoluble compounds.…”

Amino acid modified OCMC-g-Suc-β-CD nanohydrogels carrying lapatinib and ginsenoside Rg1 exhibit high anticancer activity in a zebrafish model

“…In addition, the structure of OCMC was also modified with commercial available amino acid (L-histidine and L-arginine). The two amino acids have been proved to participate in many kinds of interactions between different biomacromolecules in the human body, and therefore have been used as interesting functional groups for improving the biocompatibility of drug carriers ( Choi et al, 2012 ; Hu et al, 2018 ; Huang et al, 2019 ; Yogesh et al, 2021 ). The OCMC polymers modified with β -CD and amino acids were further used as drug carriers to load anticancer drugs lapatinib and ginsenoside Rg1 ( Figure 1 ).…”