Supervisors info:
Κωνσταντίνος Δεμέτζος, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Μαριλένα Βλάχου-Κωνσταντινίδου, Επίκουρη Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Αστέριος Πίσπας, Διευθυντής Ερευνών - Ερευνητής Ά, Ινστιτούτο Θεωρητικής και Φυσικής Χημείας, Εθνικό Ίδρυμα Ερευνών (ΕΙΕ)
Summary:
Liposomes are considered to be one of the most interesting drug delivery nano systems that provide the proper amount of the drug to the proper site in the body (pathological tissues). However, conventional liposomes present some disadvantages that reduce their therapeutic efficiency and therefore stimuli-sensitive, advanced forms of liposomes, such as pH-sensitive liposomes, have been developed, in order to overcome these disadvantages. More specifically, the combination of phospholipids and pH-responsive polymers leads to chimeric advanced drug delivery nanosystems, providing pH-sensitive liposomes. Analytically, pH-sensitive liposomes remain stable at physiological pH (7.4), but destabilize in response to environmental pH alteration, changing dramatically their conformation and eventually releasing their content. pH-sensitive liposomes exhibit increased plasma half-live, as well as increased targeting to pathological tissues, because there are many pathological states, such as tumors, presenting different pH profiles from that of normal tissues and so being novel targets of the pH-sensitive liposomes.
The aim of this study was to develop chimeric pH-sensitive liposomes, composed of hydrogenated soybean phosphatidylcholine (HSPC) phospholipid, incorporating the block copolymer poly(n-butylacrylate)-poly(acrylic acid) (PnBA-b-PAA) and the active novel anticancer agent dimethoxycurcumin (DMC), in order to improve major problems of DMC, such as rapid metabolism and poor bioavailability. PAA block exhibits pH-responsiveness, because of its regulative carboxyl group, which remains protonated under acidic pH, but is ionized under basic or neutral pH.
First, chimeric bilayers were prepared at varying ratios and pH values, where Differential Scanning Calorimetry (DSC) revealed alterations of their thermotropic properties. Subsequently, chimeric liposomes were prepared at different molar ratios and physicochemically characterized (size, size distribution, ζ-potential) at two different pH values (4.0 and 7.4), using Dynamic and Electophoretic Light Scattering (DLS/ELS) methods. Chimeric liposomes were found to retain their physicochemical characteristics over time at pH=7.4, but destabilized at acidic pH. Moreover, incorporation and release properties of DMC were also investigated. The incorporation efficiency of DMC was found to be strongly dependent on polymer presence. Release study was also carried out at pH 4.0 and 7.4, where the prepared liposomes exhibited quite different behavior. In conclusion, results indicate that the incorporation of the appropriate amount of the PnBA-b-PAA block copolymer alters the thermotropic behavior, contributes to the physicochemical stability of the liposomes over time, provides pH-sensitivity and modulates the incorporation efficiency, as well as the release of DMC.
Keywords:
nanosystems, liposomes, pH-sensitive, polymers, dimethoxycurcumin
