Amlodipine Besylate

Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. In vitro microbiological assay, besides the in vivo microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.

Protecting the kidneys by lowering systolic blood pressure (SBP) in hypertensive patients is not unequivocally settled. We tested the hypothesis that achieving lower average SBP in middle-aged and older high-risk hypertensive patients with and without type-2 diabetes mellitus through several years would clarify kidney protection.

We analyzed patients 50–80 years with no cardiovascular events during the first 6 months of drug up-titration after randomization to valsartan or amlodipine, and with 3 or more visits onwards with standardized BP measurements. Adjusted Cox analyzes compared worsened kidney function defined as a 50% rise in se-creatinine on a minimum of two occasions at least 4 weeks apart or end-stage kidney disease (ESKD) in achieved SBP quartiles and in patients who achieved SBP < 130 and 130–139 mmHg with patients whose SBP remained ≥140 mmHg.

A total of 13,803 patients were investigated of whom 4,655 had DM. Patients with DM had less worsened kidney function at SBP 130–139 mmHg (HR = 0.524, 95% CIs 0.375–0.733, n = 1849, P < 0.001) and at SBP < 130 mmHg (HR = 0.538, CIs 0.316-0.915, n = 674, P = 0.022) compared with patients at ≥ 140 mmHg. They also had less ESKD at SBP 130-139 mmHg (HR = 0.442, CIs 0.196–1.000, P = 0.050) with a similar trend at SBP < 130 mmHg and in quartile analysis with only 1 ESKD in the lowest quartile. Findings in patients without DM (n = 9,148) were similar to DM.

In high-risk hypertensive patients aged 50–80 years, with and without DM, targeting SBP of 130–139 mmHg confers kidney protection with possible further benefit at the lower target of SBP < 130 mmHg.

Trial Number NCT06395194, www.clinicaltrials.gov.