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. 2017 May 5;8(6):1337-1345.
doi: 10.1039/c7md00045f. eCollection 2017 Jun 1.

Maltodextrin modified liposomes for drug delivery through the blood-brain barrier

Zeynep Gurturk  1 , Aysen Tezcaner  1   2   3 , Ali Deniz Dalgic  2 , Seval Korkmaz  4 , Dilek Keskin  1   2   3
Affiliations

Maltodextrin modified liposomes for drug delivery through the blood-brain barrier

Zeynep Gurturk et al. Medchemcomm. .

Abstract

Central nervous system acting drugs, when administered intravenously, cannot show their effect in the brain due to the difficulty in crossing the blood-brain barrier (BBB). Levodopa is one of those drugs that are used to treat Parkinson's disease. In this study, a new liposomal levodopa delivery system that is modified with maltodextrin was developed in order to target and enhance transport through the BBB. An antioxidant, glutathione, was co-loaded in liposomes as a supportive agent and its effect on liposome stability and delivery was investigated. Glutathione co-loading had a positive effect on the viabilities of 3T3 and SH-SY5Y cells. Maltodextrin targeted liposomes showed high in vitro levodopa passage in the parallel artificial membrane permeability assay and had superior binding to MDCK cells. Results suggest that maltodextrin modification of liposomes is an effective way of targeting the BBB and the developed liposomal formulation would improve brain delivery of central nervous system agents.

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Figures

Fig. 1
Fig. 1. Conjugation of DSPE-PEG(2000) amine and carboxymethylated maltodextrin.
Fig. 2
Fig. 2. The H NMR spectrum of maltodextrin (a) and DSPE-PEG–maltodextrin conjugate (b).
Fig. 3
Fig. 3. ATR-FTIR spectra of a) maltodextrin and carboxymethylated maltodextrin (3200–3550 cm–1: hydroxyl bond (–OH), 1649–1780 cm–1: carboxyl bond (–COOH)). b) ATR-FTIR spectra of the physical mixture of DSPE-PEG(2000) amine & carboxymethylated maltodextrin and reaction product DSPE-PEG–maltodextrin (3180–3500 cm–1: amine bond (–NH2), 1649–1780 cm–1: carboxyl bond (–COOH), and 1600–1640 cm–1: amide bond (N–CO)).
Fig. 4
Fig. 4. Effect of extrusion temperature on the release of levodopa from DPPC : Chol (8 : 2, 7 : 3, and 6 : 4 m : m) liposomes prepared at a) 38 °C, b) 40 °C, c) 42 °C and d) 44 °C.
Fig. 5
Fig. 5. In vitro release profile of levodopa from a) PEGylated liposomes with 2 and 4% PEG ratios, b) targeted liposomes with 0.35 and 7% of maltodextrin conjugation and c) 0.7% maltodextrin modified targeted liposomes with 20 and 40 μM GSH co-loadings. d) In vitro release profile of GSH from 0.7% maltodextrin modified targeted liposomes with 20 and 40 μM GSH co-loadings.
Fig. 6
Fig. 6. Percent cell viabilities were calculated by accepting only cell wells as the control with 100% cell viability. Cellular viability of 3T3 cells after a) 24 hours and b) 48 hours of treatment with levodopa or levodopa and GSH (0.06 μM), α: statistically significant difference between different dose groups (p < 0.05), β: statistically significant difference between 100 μM levodopa and other different dose groups (p < 0.05); cellular viability of SH-SY5Y cells showed after c) 24 hours and d) 48 hours of treatment with levodopa or levodopa and GSH (0.06 μM); cellular viability of e) 3T3 cells and f) SH-SY5Y cells after 24 hours (1st bars) and 48 hours (2nd bars) of treatment with liposomes.
Fig. 7
Fig. 7. In vitro passive transport of levodopa solution and levodopa loaded liposomal formulations through the PAMPA-BBB model. α, β, γ, η, ι: statistically significant differences between different experimental groups after 24 hours of incubation (p < 0.05), λ, ν: statistically significant differences between different experimental groups after 48 hours of incubation (p < 0.05).
Fig. 8
Fig. 8. Comparison of in vitro passive phospholipid transport of drug loaded liposomes through the PAMPA-BBB model after 48 hours of incubation. α, β, γ, δ, ε: statistically significant differences between different experimental groups after 48 hours of incubation (p < 0.05).
Fig. 9
Fig. 9. a) Corrected fluorescence intensity of the MDCK cells after 3 and 6 hours of treatment with untargeted, (4%) PEG/LUV, and targeted, (0.7%) MD-(4%) PEG/LUV, liposomal formulations. α, β, γ: statistically significant difference between different experimental groups (p < 0.05). LSCM images of the MDCK cells treated with (b and c) Rhodamine labelled untargeted PEGylated liposome, (4%) PEG/LUV, and (d and e) Rhodamine labelled targeted liposome, (0.7%) MD-(4%) PEG/LUV (×40).
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