Development of Carvedilol-Loaded Albumin-Based Nanoparticles with Factorial Design to Optimize In Vitro and In Vivo Performance

• Published in: Pharmaceutics Vol. 15; no. 5; p. 1425
• Main Authors: Attia, Mohamed S, Radwan, Mohamed F, Ibrahim, Tarek S, Ibrahim, Tarek M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.05.2023; MDPI
• Subjects: Albumin; Antihypertensives; Bioavailability; Blood pressure; bovine serum albumin; carvedilol; Compliance; desolvation; Drug delivery systems; Drugs; Efficiency; factorial design; healthcare; Hypertension; Nanoparticles; Particle size; Patient compliance; Patients; Pharmaceuticals; Pharmacokinetics; Product development; Software; Variance analysis; United States > US; pharmacokinetic study; nanoparticles; carvedilol; desolvation; factorial design; bovine serum albumin; healthcare
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15051425

Carvedilol, an anti-hypertensive medication commonly prescribed by healthcare providers, falls under the BCS class II category due to its low-solubility and high-permeability characteristics, resulting in limited dissolution and low absorption when taken orally. Herein, carvedilol was entrapped into bovine serum albumin (BSA)-based nanoparticles using the desolvation method to obtain a controlled release profile. Carvedilol-BSA nanoparticles were prepared and optimized using 3 factorial design. The nanoparticles were characterized for their particle size (Y ), entrapment efficiency (Y ), and time to release 50% of carvedilol (Y ). The optimized formulation was assessed for its in vitro and in vivo performance by solid-state, microscopical, and pharmacokinetic evaluations. The factorial design showed that an increment of BSA concentration demonstrated a significant positive effect on Y and Y responses with a negative effect on Y response. Meanwhile, the carvedilol percentage in BSA nanoparticles represented its obvious positive impact on both Y and Y responses, along with a negative impact on Y response. The optimized nanoformulation entailed BSA at a concentration of 0.5%, whereas the carvedilol percentage was 6%. The DSC thermograms indicated the amorphization of carvedilol inside the nanoparticles, which confirmed its entrapment into the BSA structure. The plasma concentrations of carvedilol released were observable from optimized nanoparticles up to 72 h subsequent to their injection into rats, revealing their longer in vivo circulation time compared to pure carvedilol suspension. This study offers new insight into the significance of BSA-based nanoparticles in sustaining the release of carvedilol and presents a potential value-added in the remediation of hypertension.