Assembly of In-Situ Gel Containing Nano-Spanlastics of an Angiotensin II Inhibitor as a Novel Epitome for Hypertension Management: Factorial Design Optimization, In-vitro Gauging, Pharmacokinetics, and Pharmacodynamics Appraisal.

Autor: Salem HF; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt., Nafady MM; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt., Eissa EM; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt., Abdel-Sattar HH; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt., Khallaf RA; Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. rasha_khallaf@yahoo.com.
Jazyk: angličtina
Zdroj: AAPS PharmSciTech [AAPS PharmSciTech] 2024 May 16; Vol. 25 (5), pp. 115. Date of Electronic Publication: 2024 May 16.
DOI: 10.1208/s12249-024-02823-9
Abstrakt: More than 1 billion people worldwide suffer from hypertension; therefore, hypertension management has been categorized as a global health priority. Losartan potassium (LP) is an antihypertensive drug with a limited oral bioavailability of about 33% since it undergoes the initial metabolic cycle. Thus, nasal administration is a unique route to overcome first-pass metabolism. The investigation focused on the potential effects of LP-loaded spanlastic vesicles (SNVs) on LP pharmacodynamics and pharmacokinetic parameters, utilizing a thin-film hydration methodology established on a 3 1 2 2 full factorial design. Entrapment efficiency (EE%) ranged from 39.8 ± 3.87.8 to 83.8 ± 2.92% for LP-SNVs. Vesicle size (VS) varied from 205.5 ± 6.5.10 to 445.1 ± 13.52 nm, and the percentage of LP released after 8 h (Q 8h ) ranged from 30.8 ± 3.10 to 68.8 ± 1.45%. LP permeated through the nasal mucosa during 24 h and flocculated from 194.1 ± 4.90 to 435.3 ± 13.53 µg/cm2. After twenty-four hours, the optimal LP-SNVs in-situ gel showed 2.35 times more permeation through the nasal mucosa than the LP solution. It also lowered systolic blood pressure, so it is thought to be better than the reference formulation in terms of pharmacodynamics. The pharmacokinetics studies demonstrated that the intranasal LP-SNVs gel boosted its bioavailability approximately 6.36 times compared to the oral LP solution. Our research showed that intranasal LP-SNVs could be a good nanoplatform because they are well-tolerated and have possible pharmacokinetics and pharmacodynamics.
(© 2024. The Author(s).)
Databáze: MEDLINE
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