Cubosomal functionalized block copolymer platform for dual delivery of linagliptin and empagliflozin: Recent advances in synergistic strategies for maximizing control of high-risk type II diabetes

A well-made chitosan-PVP block copolymer platform was equipped with highly ordered and uniform nano-channels. This highly adhesive block copolymer platform was designed to ensure the efficient co-delivery of two synergistic-acting hypoglycemic drugs. Linagliptin oral bioavailability is 30% due to poor permeability and intestinal degradation. Its pharmacokinetics shows a non-linear profile. Empagliflozin exhibited decreased permeability and decreased solubility in aqueous media between pH 1 and 7.5. Cubosomes were functionalized as a good microdomain to guest and improve the physicochemical characteristics of drug molecules with decreased permeability and solubility. Cubosomes loaded with linagliptin (linagliptin cubosomes (LCs)) and empagliflozin (empagliflozin cubosomes ECs) were separately prepared using the top-down method and optimized by applying 2³ factorial design. Optimized cubosomal systems LCs (F3) and ECs (F4) were incorporated into a chitosan-PVP gel to obtain dual cubosome-loaded platforms (LECF) optimized through 2² factorial design. The permeation study from the optimized LECF (C1) ensured enhanced empagliflozin permeation alongside continued efflux for linagliptin, resolving potential risks due to its non-linear plasma profile. The in-vivo study revealed that AUC_(0–∞) of linagliptin and empagliflozin was enhanced by 2- and threefold, respectively. Therefore, the chitosan-PVP block copolymer platform buccal application for the co-delivery of linagliptin and empagliflozin could contribute to enhanced clinical effectiveness in treating diabetes.

Materials

Lin and Emp were provided by ATCO Pharma and Apex Pharma, respectively. Other materials were baricitinib (IS) (BDR Life Science Private Limited), isopropyl myristate (IPM) (QUALIKEMS Fine Chemicals, Pvt, Ltd., India), glyceryl monooleate (GMO) and chitosan (MW 310000–375000 Da) (Sigma-Aldrich, U.S.A), L-alpha-lecithin (MW: 750.00 g/mol) (Acros Organics, USA), Kolliphor RH40 and Pluronic F127 (PF127) (Sigma-Aldrich, Germany), polyvinylpyrrolidone K30 (PVP K30) (Fluka Chem, Germany), glycerol (El-Nasr Pharmaceutical Chemicals, Egypt), and synthetic cellulose acetate membrane with a weight cut-off of 12,000–14,000 (SERVA Electrophoresis, Germany).

Download the full study as PDF here: Cubosomal functionalized block copolymer platform for dual delivery of linagliptin and empagliflozin: Recent advances in synergistic strategies for maximizing control of high-risk type II diabetes

or read it here

Hammad, R.W., Sanad, R.AB., Abdelmalak, N.S. et al. Cubosomal functionalized block copolymer platform for dual delivery of linagliptin and empagliflozin: Recent advances in synergistic strategies for maximizing control of high-risk type II diabetes. Drug Deliv. and Transl. Res. (2023).
https://doi.org/10.1007/s13346-023-01423-7

See the webinar:

“Rational Selection of Cyclodextrins for the Solubilization of Poorly Soluble Oral Drugs”, 8. November 2023:

Get more information & register here for free: