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  • Title: Development of stimuli-responsive lyotropic liquid crystalline nanoparticles targeting lysosomes: Physicochemical, morphological and drug release studies.
    Author: Chountoulesi M, Perinelli DR, Forys A, Chrysostomou V, Kaminari A, Bonacucina G, Trzebicka B, Pispas S, Demetzos C.
    Journal: Int J Pharm; 2023 Jan 05; 630():122440. PubMed ID: 36436746.
    Abstract:
    The abilities of sub-cellular targeting and stimuli-responsiveness are critical challenges in pharmaceutical nanotechnology. In the present study, glyceryl monooleate (GMO)-based non-lamellar lyotropic liquid crystalline nanoparticles were stabilized by the poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), either used alone or in combination with other polymers as co-stabilizers. The systems were designed to perform simultaneously sub-cellular targeting, stimuli-responsiveness and to exhibit stealthiness. The physicochemical characteristics and fractal dimensions of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. The analyzed properties, including the responsiveness to pH and temperature, were found to be dependent on the combination of the polymeric stabilizers. The subcellular localization was monitored by confocal microscopy, revealing targeting to lysosomes. Subsequently, resveratrol was loaded into the nanosystems, the entrapment efficiency was investigated and in vitro release studies were carried out at different conditions, in which a stimuli-triggered drug release profile was achieved. In conclusion, the proposed multi-functional nanosystems can be considered as potentially stealth, stimuli-responsive drug delivery nanocarriers, with targeting ability to lysosomes and presenting a stimuli-triggered drug release profile.
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