Improving the bioavailability and therapeutic efficacy of felodipine for the control of diabetes-associated atherosclerosis: In vitro and in vivo characterization

• Published in: International journal of pharmaceutics Vol. 661; p. 124395
• Main Authors: Mahmoud, Dina M., El-Ela, Fatma I. Abo, Fouad, Amr Gamal, Belal, Amany, Ali, Mohamed A.M., Ghoneim, Mohammed M., Almeheyawi, Rania N, Attia, Mary Eskander, Mahmoud, Tamer M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2024
• Subjects: Animals; Atherosclerosis; Atherosclerosis - drug therapy; Bioavailability; Biological Availability; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - chemistry; Calcium Channel Blockers - pharmacokinetics; Chitosan; Chitosan - chemistry; Cholesterol - chemistry; Diabetes; Diabetes Complications - drug therapy; Diabetes Mellitus, Experimental - drug therapy; Drug Carriers - chemistry; Drug Liberation; Felodipine; Felodipine - administration & dosage; Felodipine - chemistry; Felodipine - pharmacokinetics; Hydrogels - chemistry; Hydrogen-Ion Concentration; Invasomes; Male; Phospholipids - chemistry; Rats; Rats, Sprague-Dawley; Solubility; EE; R2; FLI; CCB; PS; FLL; Bioavailability; Jss; IPHFI; FDN; SD; ΔH; ANOVA; DSC; Atherosclerosis; Diabetes; Chitosan; AIC; MSC; Invasomes; TEM; Felodipine
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124395

[Display omitted] •The study aimed to develop a nasal in-situ pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) formulation to improve the release, permeation, bioavailability, and efficacy of felodipine as a potential atherosclerosis treatment.•The nasal IPHFI formulation significantly increased the release and permeation of felodipine relative to free felodipine by 2.99 and 3fold, respectively.•The nasal IPHFI formulation increased felodipine’s bioavailability by 3.37-fold.•The nasal IPHFI formulation decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Felodipine has proven to be effective as an atherosclerosis therapy because it increases blood flow to the vessel wall. However, the poor solubility, low bioavailability, and hepatic first-pass metabolism of oral felodipine compromise its therapeutic effectiveness. The study’s goal is to create a nasal pH-sensitive hydrogel of felodipine-loaded invasomes (IPHFI) that will improve felodipine’s release, permeation, bioavailability, and efficacy as a potential diabetes-associated atherosclerosis therapy. According to the pre-formulation study, the felodipine-loaded invasomes formulation composed of phospholipid (3%w/v), cholesterol (0.16%w/v), ethanol (3%v/v) and cineole (1%v/v) was chosen as the optimum formulation. The optimum formulation was characterized in vitro and then mixed with a mixture of chitosan and glyceryl monooleate to make the IPHFI formulation. The IPHFI formulation enhanced the release and permeation of felodipine by 2.99 and 3-fold, respectively. To assess the efficacy and bioavailability of the IPHFI formulation, it was studied in vivo using an experimental atherosclerosis rat model. Compared to oral free felodipine, the nasal administration of the IPHFI formulation increased the bioavailability by 3.37-fold and decreased the serum cholesterol, triglycerides, LDL, and calcification score by 1.56, 1.53, 1.80, and 1.18 ratios, respectively. Thus, nasal IPHFI formulation may represent a promising diabetes-associated atherosclerosis therapy.