Liposomes containing cyclodextrins or meglumine to solubilize and improve the bioavailability of poorly soluble drugs

Abstract

Poorly soluble drug-loaded liposomes are well known for their ability to solubilize and improve the bioavailability of the carried molecules, and may provide benefits as oral drug delivery systems. In this work, we aim to evaluate the effect of the incorporation of β-cyclodextrin (βCD), methyl-βCD (MβCD), hydroxypropil-βCD (HPβCD) and meglumine (MEG) in liposomes for the oral delivery of the poorly water-soluble drugs, sulfamerazine (SMR) and indomethacin (INM). Liposomes with egg phosphatidylcholine (PC) and cholesterol (CHO), incorporating SMR or INM as plain drug or inclusion complexes, were prepared using the thin film hydration method or dehydration-rehydration method, respectively. The systems were characterized by particle size, polydispersity and zeta potential measurements, and drug-component interaction studies were performed by 1H NMR. Liposome stability in presence of SMR, INM, CD and MEG was determined by the retention of vesicle encapsulated calcein after incubation in solutions of pH 7.4, at 37 °C for up to 48 h. Drug entrapment, as well as drug release, were estimated for all liposome types prepared. The 1H NMR studies revealed that the drugs presented interaction with lipids of the liposomes, suggesting the location of the drugs in the lipid bilayer. The liposomes presented high stability in the presence of the drugs, βCD, HPβCD or MEG. The highest entrapment values were achieved for SMR and INM with PC:CHO 3:1 liposomes when MEG and HPβCD were used, respectively (5636.28 and 439.54 mmol/mol), meaning that 18 and 43 times higher incorporation of SMR and INM were achieved in comparison with the ligand-free formulation. The in-vitro release studies showed a strong influence of the ligands on the delivery of the drugs from the liposomes.