Objectives: Deformable liposomes (DL) are successfully being exploited to enhance the penetration of several compounds in the skin. Nevertheless, the lack of cholesterol along with the presence of a destabilizing agent in the bilayer of such vesicles favors the drug leakage, mainly in the case of hydrophobic compounds. This work aimed to develop suitable strategies to stabilize the lipid bilayer, without compromising the deformability properties of DL. Two approaches were pursuit, relying on 1) the steric stabilization of the bilayer by decoration with hyaluronan (HA-DL) or 2) the tuning of a “matryoshka” system by loading drug micelles in the aqueous core of DL (M-DL). Methods: DL were prepared by thin film hydration method. Nifedipine was selected as model drug. Results: DL composed of egg-phosphatidylcholine and Tween 80 (T80) at 95:5 and 85:15 w/w ratios after one month of storage gave a nifedipine leakage of 51.8 and 58.2%, respectively. Drug crystals were detectable in the bulk after 2 months. In the HA-DL series, the labelling of HA at 0.5% molar concentration caused a slight decrease of the drug loss (41.2%) whereas a significant improvement of the dug retention was obtained using 3% molar HA. Nevertheless, such HA amount definitively compromised the deformability of the vesicles. In the M-DL system any drug loss was revealed after one month of storage. Accordingly, the M-DL system showed a reduction of the drug release rate. 95:5 DL released 50% of the loaded drug after 22 hours against the 20% of M-DL. Also in the case of the more fluid system (15% T80) the flux of nifedipine was decreased of almost two times in the M-DL with respect to DL (1.4±0.2 vs 2.7±0.1 µg/h). Conclusions: M-DL approach results to be more versatile than the HA decoration, allowing the development of deformable carriers intended for cutaneous application.

Novel approaches to prevent drug leakage from deformable liposomes / S. Franze', P. Minghetti, F. Cilurzo. ((Intervento presentato al convegno EUFEPS Annual Meeting 2018- Crossing Barriers for Future Medicines tenutosi a Athens nel 2018.

Novel approaches to prevent drug leakage from deformable liposomes

S. Franze'
Primo
;
P. Minghetti
Secondo
;
F. Cilurzo
Ultimo
2018

Abstract

Objectives: Deformable liposomes (DL) are successfully being exploited to enhance the penetration of several compounds in the skin. Nevertheless, the lack of cholesterol along with the presence of a destabilizing agent in the bilayer of such vesicles favors the drug leakage, mainly in the case of hydrophobic compounds. This work aimed to develop suitable strategies to stabilize the lipid bilayer, without compromising the deformability properties of DL. Two approaches were pursuit, relying on 1) the steric stabilization of the bilayer by decoration with hyaluronan (HA-DL) or 2) the tuning of a “matryoshka” system by loading drug micelles in the aqueous core of DL (M-DL). Methods: DL were prepared by thin film hydration method. Nifedipine was selected as model drug. Results: DL composed of egg-phosphatidylcholine and Tween 80 (T80) at 95:5 and 85:15 w/w ratios after one month of storage gave a nifedipine leakage of 51.8 and 58.2%, respectively. Drug crystals were detectable in the bulk after 2 months. In the HA-DL series, the labelling of HA at 0.5% molar concentration caused a slight decrease of the drug loss (41.2%) whereas a significant improvement of the dug retention was obtained using 3% molar HA. Nevertheless, such HA amount definitively compromised the deformability of the vesicles. In the M-DL system any drug loss was revealed after one month of storage. Accordingly, the M-DL system showed a reduction of the drug release rate. 95:5 DL released 50% of the loaded drug after 22 hours against the 20% of M-DL. Also in the case of the more fluid system (15% T80) the flux of nifedipine was decreased of almost two times in the M-DL with respect to DL (1.4±0.2 vs 2.7±0.1 µg/h). Conclusions: M-DL approach results to be more versatile than the HA decoration, allowing the development of deformable carriers intended for cutaneous application.
26-mag-2018
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
Novel approaches to prevent drug leakage from deformable liposomes / S. Franze', P. Minghetti, F. Cilurzo. ((Intervento presentato al convegno EUFEPS Annual Meeting 2018- Crossing Barriers for Future Medicines tenutosi a Athens nel 2018.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/602998
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