.2017 Mar 4;15(3):64.

doi: 10.3390/md15030064.

Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes

Toril Andersen¹, Ekaterina Mishchenko², Gøril Eide Flaten³, Johanna U Ericson Sollid⁴, Sofia Mattsson⁵, Ingunn Tho⁶, Nataša Škalko-Basnet⁷

Affiliations

¹ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. toril_andersen@hotmail.com.
² Host Microbe Interactions Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. ekaterina.mishchenko@uit.no.
³ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. goril.flaten@uit.no.
⁴ Host Microbe Interactions Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. johanna.e.sollid@uit.no.
⁵ Department of Pharmacology and Clinical Neuroscience, Division of Clinical Pharmacology, Umeå University, SE-90187 Umeå, Sweden. sofia.mattsson@pharm.umu.se.
⁶ Personalized Dosage Form Design Research Group, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway. ingunn.tho@farmasi.uio.no.
⁷ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. natasa.skalko-basnet@uit.no.

PMID:28273850
PMCID: PMC5367021
DOI: 10.3390/md15030064

Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes

Toril Andersen et al. Mar Drugs.2017.

.2017 Mar 4;15(3):64.

doi: 10.3390/md15030064.

Authors

Toril Andersen¹, Ekaterina Mishchenko², Gøril Eide Flaten³, Johanna U Ericson Sollid⁴, Sofia Mattsson⁵, Ingunn Tho⁶, Nataša Škalko-Basnet⁷

Affiliations

¹ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. toril_andersen@hotmail.com.
² Host Microbe Interactions Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. ekaterina.mishchenko@uit.no.
³ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. goril.flaten@uit.no.
⁴ Host Microbe Interactions Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. johanna.e.sollid@uit.no.
⁵ Department of Pharmacology and Clinical Neuroscience, Division of Clinical Pharmacology, Umeå University, SE-90187 Umeå, Sweden. sofia.mattsson@pharm.umu.se.
⁶ Personalized Dosage Form Design Research Group, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway. ingunn.tho@farmasi.uio.no.
⁷ Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø The Arctic University of Norway, 9037 Tromsø, Norway. natasa.skalko-basnet@uit.no.

PMID:28273850
PMCID: PMC5367021
DOI: 10.3390/md15030064

Abstract

Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great improvement in vaginal therapy; the chitosan-based nanosystem could both provide antifungal effects and simultaneously deliver antibacterial drugs. We prepared chitosan-containing liposomes, chitosomes, where chitosan is both embedded in liposomes and surface-available as a coating layer. For antimicrobial activity, we entrapped metronidazole as a model drug. To prove that mucoadhesivness alone is not sufficient for successful delivery, we used Carbopol-containing liposomes as a control. All vesicles were characterized for their size, zeta potential, entrapment efficiency, and in vitro drug release. Chitosan-containing liposomes were able to assure the prolonged release of metronidazole. Their antifungal activity was evaluated in aC. albicans model; chitosan-containing liposomes exhibited a potent ability to inhibit the growth ofC. albicans. The presence of chitosan was crucial for the system's antifungal activity. The antifungal efficacy of chitosomes combined with antibacterial potential of the entrapped metronidazole could offer improved efficacy in the treatment of mixed/complex vaginal infections.

Keywords: Candida albicans; chitosan; drug delivery; liposomes; metronidazole; vaginal therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure A1**
Schematic presentation of the preparation method.

**Figure 1**
Entrapment efficiency of metronidazole in chitosan-containing liposomes, Carbopol-containing liposomes, and plain liposomes. All liposomes were sonicated for one minute, unless stated differently. All values represent the mean ± SD (n = 3).

**Figure 2**
Cumulative release of metronidazole from different types of liposomes at pH 7. All liposomes were sonicated for one minute unless stated differently. The values represent the mean ± SD (n = 3).

**Figure 3**
Representative photographs of theC. albicans growth on agar plates in the presence of different liposomal formulations; (A) Chitosan-containing liposomes (no drug); (B) Chitosan-containing liposomes (MTZ); (C) Carbopol-containing liposomes (MTZ); (D) plain liposomes (MTZ). Each sector contains an aliquot from a test well with a dilution of a formulation; aliquots were inoculated anticlockwise, i.e., from the highest concentration in sector 1 to the lowest concentration in sector 8. White spots represent the ‘lawn’ growth ofC. albicans. The inhibition ofC. albicans growth is indicated by the absence of white spots.

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Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes

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Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes

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