RESUMO
Background: Angiotensin-converting enzyme inhibitors (ACEIs) are prescribed for individuals with high cardiovascular (CV) risk; however, persistent cough limits the use of ACEIs in a large number of patients. The current study aimed to identify the genetic variants in the SLCO1B1 gene that might be associated with ACEI-related cough in a Pakistani hypertensive population. Methods: A prospective cohort study was conducted at a tertiary care hospital in Pakistan. A total of 74 patients who had been treated with ACEIs were recruited through a convenient sampling method. The study was approved by the Institutional Review Board & Ethics Committee of the Shifa International Hospital, Islamabad. Patients provided 2 ml of blood for sequencing after signing informed consent. Partial gene sequencing of SLCO1B1 was carried out to find single nucleotide polymorphisms (SNPs) and haplotypes. Results: It was found, through a structured questionnaire, that thirty-eight (38) patients experienced cough within 2 weeks of ACEI administration and were considered as a case group (cough), and thirty-six (36) patients were considered as a control group (no cough). The incidence of cough was 51%. We found six different SNPs and 9 haplotypes in the partial gene sequences of SLCO1B1. Haplotype H4 was associated significantly with cough after adjusting for sex and smoking status. Other SNPs and haplotypes were not significantly associated with ACE-Is-induced cough. Conclusion: These findings emphasize the significance of SLCO1B1 genetic variants, specifically H4, as a potential predictor of ACEI-induced cough. It could be included in clinical practice as a possible risk factor for ACEI-induced cough once confirmed in larger clinical trials with bigger sample sizes. The replication of these findings in larger and more diverse populations is likely to contribute to the therapeutic use of ACEIs by predicting ACEI-induced cough.
RESUMO
Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings.