Improving Oral Bioavailability and Pharmacokinetics of Liposomal Metformin by Glycerolphosphate–Chitosan Microcomplexation

Abstract

Abstract. The purpose of this study was to develop a new delivery system capable of improving bioavailability and controlling release of hydrophilic drugs. Metformin-loaded liposomes were prepared and to improve their stability surface was coated with chitosan cross-linked with the biocompatible β-glycerolphosphate. X-ray diffraction, differential scanning calorimetry, as well as rheological analysis were performed to investigate interactions between chitosan and β-glycerolphosphate molecules. The entrapment of liposomes into the chitosan-β-glycerolphosphate network was assessed by scanning electron microscopy and transmission electron microscopy. Swelling and mucoadhesive properties as well as drug release were evaluated in vitro while the drug oral bioavailability was evaluated in vivo on Wistar rats. Results clearly showed that, compared to control, the proposed microcomplexes led to a 2.5-fold increase of metformin T max with a 40% augmentation of the AUC/D value.

Adapting liposomes for oral drug delivery

“…Further observation of enhanced oral bioavailability confirms the effectiveness of coating with chitosan 91 . Moreover, the stability of chitosan-coated liposomes can be strengthened by subsequent cross-linking using β -glycerolphosphate 92 .…”

Application of pH-Responsive Fucoidan/Chitosan Nanoparticles to Improve Oral Quercetin Delivery

“…As an approach to overcoming the described limitations, some authors combined the best features of lipid systems with polymers to allow better stability and delivery of the compounds of interest. Some of the strategies involved the coating of liposomes with chitosan to achieve controlled and prolonged vesicle uptake via lung delivery [34] or to improve oral bioavailability and sustained release of hydrophilic drugs [35,36]. This approach was also explored to elicit an intestinal preferential release of quercetin, using a hybrid system composed of liposomes coated with cross-linked chitosan [37].…”

Calcium alginate microspheres containing metformin hydrochloride niosomes and chitosomes aimed for oral therapy of type 2 diabetes mellitus

“…Chitosan is a polymer well known for its attractive properties, such as biocompatibility, biodegradability and bioadhesivity (Gulbake and Jain, 2012). Chitosomes maintained the positive properties of liposomes, but showed greater stability and provided longer residence times in the gastrointestinal tract, in virtue of their mucoadhesion properties (Takeuchi et al, 2003(Takeuchi et al, , 2005Werle and Takeuchi, 2009;Manconi et al, 2010Manconi et al, , 2013Shao et al, 2015;Caddeo et al, 2016).…”