Temperature-sensitive poly(N-(2-hydroxypropyl)methacrylamide mono/dilactate)-coated liposomes for triggered contents release.
We prepared thermosensitive poly( N-(2-hydroxypropyl)methacrylamide mono/dilactate) (pHPMA mono/dilactate) polymer and studied temperature-triggered contents release from polymer-coated liposomes. HPMA mono/dilactate polymer was synthesized with a cholesterol anchor suitable for incorporation in the liposomal bilayers and with a cloud point (CP) temperature of the polymer slightly above normal body temperature (42 degrees C). Dynamic light scattering (DLS) measurements showed that whereas the size of noncoated liposomes remained stable upon raising the temperature from 25 to 46 degrees C, polymer-coated liposomes aggregated around 43 degrees C. Also, noncoated liposomes loaded with calcein showed hardly any leakage of the fluorescent marker when heated to 46 degrees C. However, polymer-coated liposomes showed a high degree of temperature-triggered calcein release above the CP of the polymer. Likely, liposome aggregation and bilayer destabilization are triggered because of the precipitation of the thermosensitive polymer above its CP onto the liposomal bilayers, followed by permeabilization of the liposomal membrane. This study demonstrates that liposomes surface-modified with HPMA mono/dilactate copolymer are attractive systems for achieving temperature-triggered contents release.
Paasonen
Lauri
L
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands. Lauri.Paasonen@helsinki.fi
Romberg
Birgit
B
Storm
Gert
G
Yliperttula
Marjo
M
Urtti
Arto
A
Hennink
Wim E
WE
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D005452:Fluoresceins; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013696:Temperature
D000178:Acrylamides; D005452:Fluoresceins; D007773:Lactates; D008081:Liposomes; D011109:Polymethacrylic Acids; C509680:poly(N-(2-hydroxypropyl) methacrylamide lactate); C525969:poly(N-(2-hydroxypropyl)methacrylamide dilactate); D002784:Cholesterol; C007740:fluorexon