A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and characterized. 3TC was coupled to dextran ( approximately 25 kDa) using a succinate linker, and the in vitro and in vivo behavior of the conjugate was studied using newly developed size-exclusion and reversed-phase analytical methods. Synthesized 3TCSD had a purity of >99% with a degree of substitution of 6.5 mg of 3TC per 100 mg of the conjugate. Furthermore, the developed assays were precise and accurate in the concentration ranges of 0.125-20, 0.36-18, and 1-50 microg/mL for 3TC, 3TC succinate (3TCS), and 3TCSD, respectively. In vitro, the conjugate slowly released 3TC in the presence of rat liver lysosomes, whereas it was stable in the corresponding buffer. In vivo in rats, conjugation of 3TC to dextran resulted in 40- and 7-fold decreases in the clearance and volume of distribution of the drug, respectively. However, the accumulation of the conjugated 3TC in the liver was 50-fold higher than that of the parent drug. The high accumulation of the conjugate in the liver was associated with a gradual and sustained release of 3TC in the liver. These studies indicate the feasibility of the synthesis of 3TCS-dextran and its potential use for the selective delivery of 3TC to the liver.

Download full-text PDF

Source
http://dx.doi.org/10.1021/bc700193dDOI Listing

Publication Analysis

Top Keywords

3tc liver
12
3tc
10
liver
6
conjugate
5
synthesis analysis
4
analysis vitro
4
vitro characterization
4
characterization vivo
4
vivo disposition
4
disposition lamivudine-dextran
4

Similar Publications

Objective: This study aims to investigate the differences of clinical indices in HIV patients between three different first-line antiretroviral treatment strategies in Yunnan Province, China. Furthermore, the hematologic system, liver function, kidney function, blood lipid levels of HIV patients and its association with CD4+ count, CD8+ count, CD4/CD8 ratio and antiretroviral treatment were also assessed.

Methods: This retrospective cohort study included 81 participants who underwent highly active antiretroviral treatment from September 2009 to September 2019.

View Article and Find Full Text PDF
Article Synopsis
  • The study assessed the effects of hepatic steatosis-insulin resistance (HS-IR) and liver fibrosis (LF) on the development of type 2 diabetes mellitus (DM2) using specific measures (TyG and FIB-4).
  • The incidence rates of DM2 were recorded as 12.9 per 1000 person-years for HS-IR and 9.8 per 1000 for LF.
  • There was a significant reduction in the prevalence of HS-IR at both 12 and 24 months when treated with TDF combined with either 3TC or FTC and RPV, indicating beneficial treatment outcomes.
View Article and Find Full Text PDF

Purpose: To determine the incidence of non-alcoholic fatty liver disease (NAFLD) by non-invasive methods in people living with HIV (PLWH).

Methods: Prospective cohort, in PLWH naïve to antiretroviral therapy, starting bictegravir (BIC) or dolutegravir (DTG) at the Hospital de Infectología "La Raza", in Mexico City, from February 2021 to August 2023. We measured at baseline and 48 weeks triglycerides and glucose index (TyG), fatty liver index (FLI), hepatic steatosis index (HSI) and liver ultrasonography; relative risk (RR) for developing NAFLD was determined.

View Article and Find Full Text PDF

Introduction: This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status.

Methods: Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereafter, experimental animals in each diet group were further randomized into four treatment sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamorelin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and diets combined for 9 weeks.

View Article and Find Full Text PDF

Introduction: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!