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Fulltext Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations

Sivadasan D, Venkatesan K, Mohamed JMM, Alqahtani S, Asiri YI, Faisal MM, et al.

Sci Rep, 2024 Mar 16;14(1):6361.
PMID: 38493177 DOI: 10.1038/s41598-024-55953-2

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.
The Impact of Close Proximity of Left Atrium to Descending Aorta on Left Inferior Pulmonary Vein Triggers or Drivers of Atrial Fibrillation: A Risk Score Model

Bautista JAL, Liu CM, Ibrahim AE, Lo LW, Chung FP, Hu YF, et al.

Heart Rhythm, 2024 Jul 10.
PMID: 38997056 DOI: 10.1016/j.hrthm.2024.06.062

BACKGROUND: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers.
OBJECTIVES: To assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures.
METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from pre-ablation pulmonary vein computed tomography. Patients were categorized based on the presence of LIPV triggers and/or drivers. Multivariate logistic regression was used to identify risk factors.
RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers and/or drivers. The Dao-LIPV distance had a better predictive performance (AUC: 0.70) compared to persistent AF (AUC: 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤ 2.5 mm (Odds ratio [OR] 3.96 [95% CI 2.15-7.29], p <0.001) and persistent AF (OR 1.73 [95% CI 1.02-2.94], p=0.044) were independent predictors for the presence of LIPV triggers and/or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤ 2.5mm (11.4%), and both (15.0%).
CONCLUSIONS: The close proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤ 2.5mm significantly increase the risk of LIPV triggers/drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.

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