Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
Received 28 July 2019
Accepted for publication 25 October 2019
Published 25 November 2019 Volume 2019:14 Pages 9127—9138
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo
Bader B Alsulays,1 Md Khalid Anwer,1 Gamal A Soliman,2,3 Sultan M Alshehri,4 El-Sayed Khafagy1,5
1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmacology, College of Veterinary Medicine, Cairo University, Cairo 12211, Egypt; 3Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj 11942, Saudi Arabia; 4Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 415-22, Egypt
Correspondence: El-Sayed Khafagy
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, PO Box 173, AlKharj 11942, Saudi Arabia
Tel +966 533564286
Fax +966 115886001
Purpose: This study evaluated the stereoisomeric effect of L- and D-penetratin—cell-penetrating peptides (CPPs)—incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS).
Methods: Insulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin.
Results: The mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and −17.0 to −23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t1/2) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively.
Conclusion: Penetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration.
Keywords: cell-penetrating peptides, penetratin, stereochemistry, solid lipid nanoparticles, enzymatic degradation, oral insulin bioavailability