The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformat...The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.展开更多
Sugar fatty acid esters (SFAE) are a class of synthetic emulsifiers used in the food, pharmaceutical, and personal care industries. The influence of the fatty acid chain length on the emulsification properties of lact...Sugar fatty acid esters (SFAE) are a class of synthetic emulsifiers used in the food, pharmaceutical, and personal care industries. The influence of the fatty acid chain length on the emulsification properties of lactose fatty acid esters (LFAE) including lactose monooctanoate (LMO), lactose monodecanoate (LMD), lactose monolaurate (LML) and lactose monomyristate (LMM) was investigated in this study. The stability of the emulsions as well as the oil droplet size distribution in 20% soybean oil-in-water emulsions was measured at 0.1%, 0.25% and 0.5% of LFAE concentrations. In order of LFAE with the strongest emulsion stabilization characteristics were LML, LMD, LMO and LMM. Oil droplet distributions resulted in the same trend, with LML and LMD maintaining the smallest droplet sizes and thus the most stable emulsion. The hydrophilic-lipophilic balance (HLB) and critical micelle concentrations were determined for each LFAE. An increase in HLB value was seen with an increased CMC value for each LFAE, showing the strength of the linear relationship between these two measured values. Additionally, there was a decrease in HLB and CMC values with a decrease in the fatty acid chain length of each LFAE. This research showed that LML and LMD formed more stable emulsions, even with HLB and CMC values higher than those of LMM suggesting HLB and CMC values alone do not predict emulsifier effectiveness.展开更多
文摘The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.
文摘Sugar fatty acid esters (SFAE) are a class of synthetic emulsifiers used in the food, pharmaceutical, and personal care industries. The influence of the fatty acid chain length on the emulsification properties of lactose fatty acid esters (LFAE) including lactose monooctanoate (LMO), lactose monodecanoate (LMD), lactose monolaurate (LML) and lactose monomyristate (LMM) was investigated in this study. The stability of the emulsions as well as the oil droplet size distribution in 20% soybean oil-in-water emulsions was measured at 0.1%, 0.25% and 0.5% of LFAE concentrations. In order of LFAE with the strongest emulsion stabilization characteristics were LML, LMD, LMO and LMM. Oil droplet distributions resulted in the same trend, with LML and LMD maintaining the smallest droplet sizes and thus the most stable emulsion. The hydrophilic-lipophilic balance (HLB) and critical micelle concentrations were determined for each LFAE. An increase in HLB value was seen with an increased CMC value for each LFAE, showing the strength of the linear relationship between these two measured values. Additionally, there was a decrease in HLB and CMC values with a decrease in the fatty acid chain length of each LFAE. This research showed that LML and LMD formed more stable emulsions, even with HLB and CMC values higher than those of LMM suggesting HLB and CMC values alone do not predict emulsifier effectiveness.
