Development of innovative delivery systems to counteract vaginal infections

Giordani, Barbara (2020) Development of innovative delivery systems to counteract vaginal infections, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze biotecnologiche e farmaceutiche, 32 Ciclo. DOI 10.6092/unibo/amsdottorato/9390.
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Abstract

The present thesis aimed to overcome some drawbacks associated with the currently available therapies for vaginal dysbiosis and with the use of conventional dosage forms. Formulations based on well-established drugs (chlorhexidine and econazole nitrate) delivered in innovative systems and formulations containing alternative active agents (probiotics cells and polyphenols) have been taken into account. In paper 1 Bifidobacterium breve BC204 was isolated and indagated for its probiotic potential. B. breve was subsequently protected by spray-drying encapsulation and formulated inside orally time-dependent erodible lipid tablets, with the aim to exert beneficial effects both at intestinal and vaginal level. The final dosage forms provided high loading and survival of B. breve BC204, as well as a delayed release and mucoadhesive abilities. In paper 2 chlorhexidine was first complexed with different polyanion polymers, then freeze-dried matrices containing either the isolated complex or the complex along with free drug and polymers were prepared. Hyaluronate-based matrix showed a flexible structure, the best hydration and mucoadhesive properties, the best profile of drug release and excellent antimicrobial properties. In paper 3 econazole was vaginally delivered in phosphatidylcholine vesicles containing a biosurfactant, selected as “green” alternative surfactant, isolated from a vaginal probiotic strain. The biosurfactant revealed a peptide-like structure and good surfactant and emulsifying properties. Mixed vesicles presented optimal diameter range for vaginal administration, high encapsulation efficiency and mucoadhesion ability, as well as a sustained drug release. They also significantly improved the ability of econazole to eradicate Candida biofilm. In paper 4 vaginally delivered liposomes containing two polyphenols (quercetin and gallic acid) were proposed as alternative to conventional antifungals to overcome the problem of azole resistance. They showed good entrapment efficiencies and better release profiles compared with formulations containing only one polyphenol. Moreover, liposomes displayed strong anti-oxidant and anti-inflammatory activities, resulted not cytotoxic to cells and inhibited Candida proliferation.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Giordani, Barbara
Supervisore
Dottorato di ricerca
Ciclo
32
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
vaginal delivery; urogenital infections; probiotics; microencapsulation; spray-drying; chlorexidine; freeze-drying; mucoadhesion; polymeric matrices; biosurfactant; econazole; liposomes; Candida; quercetin; gallic acid
URN:NBN
DOI
10.6092/unibo/amsdottorato/9390
Data di discussione
3 Aprile 2020
URI

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