Temperature-dependent drug release from DPPC:C12H25-PNIPAM-COOH liposomes: control of the drug loading/release by modulation of the nanocarriers' components

Abstract

Novel polymer-modified thermosensitive liposomes were developed for the delivery of indomethacin in order to control its release profile. When attached to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, the end functionalized C12H25-poly(N-isopropylacrylamide)-COOH (C12H25-PNIPAM-COOH) polymer was membrane-disruptive in a temperature-dependent manner. The interest for this polymer is driven by its famous lower critical solution temperature (LCST) behavior, where heating an aqueous solution of PNIPAM above 32°C induces nanophase separation and polymer chain aggregation. The physicochemical/structural behavior of these polymer-modified thermosensitive liposomes was found to depend on the PNIPAM:lipid molar ratio and the composition of the polymeric guest. The incorporation of PNIPAM has caused alterations in the thermotropic behavior of DPPC liposomes, as the differential scanning calorimetry (DSC) experiments revealed. The drug loading and the release were found to be strongly dependent on the thermotropic characteristics of the PNIPAM grafted DPPC liposomes. Namely, the in vitro release is immediate at 37°C (>LCST) ("burst" effect), while the prepared mixed nanocarriers did not release the encapsulated bioactive substance at <32°C (<LCST). Thus, the thermosensitivity and the drug loading/release properties of the prepared formulations can be modulated by varying the ratio of DPPC/PNIPAM components, as well as the molecular characteristics of the polymeric guest.

Keywords: Burst “effect”; Differential scanning calorimetry; Drug release; Poly(N-isopropylacrylamide); Thermosensitive liposomes.