Synthesis of chitosan‐based thermo‐ and pH‐responsive porous nanoparticles by temperature‐dependent self‐assembly method and their application in drug release

Abstract

In this research, thermo‐ and pH‐responsive chitosan‐based porous nanoparticles were prepared by the temperature‐dependent self assembly method. The chitosan‐graft‐poly(N‐isopropylacrylamide) (CS‐g‐PNIPAAm) copolymer solution was prepared through polymerization of N‐isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using cerium ammounium nitrate as the initiator. Then, CS‐g‐PNIPAAm solution was diluted by deionized water and heated to 40 °C for CS‐g‐PNIPAAm self‐assembly. After that, CS‐g‐PNIPAAm assembled to form micelles in which shell layer was CS. Crosslinking agent was used to reinforce the micelle structure to form nanoparticle. The molar ratio of CS/NIPAAm in the feed mixture was changed to investigate its effect on structure, morphology, thermal‐ and pH‐responsive properties of the nanoparticles. TEM images showed that a porous structure of nanoparticles was developed. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli‐responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in‐vitro release experiment. These porous particles with environmentally sensitive properties are expected to be utilized in hydrophilic drug delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5126–5136, 2009

Stimulus-responsive polymeric nanoparticles for biomedical applications

“…Because pH and temperature are the predominant stimulus signals, pH-and thermo-responsive nanoparticles containing both pH-and thermo-responsive units have been extensively studied [12,46,[68][69][70][71][72][73][74][75][76][77][78]. For pH/thermal stimulusresponsive systems, the most commonly used thermosensitive and pH-sensitive segments are poly(N-isopropylacrylamide) (PNIPPAm) and poly(acrylic acid) (PAA), respectively [4,27,69,79].…”

“…Researchers used free radicals, which were produced during oxidizing the pyranose ring of polysaccharide, to initiate the polymerization of NIPAAm monomer to obtain pH-/thermo-sensitive copolymers [78] with pH-and thermo-sensitive properties due to the existence of amino groups in chitosan chains and PNIPAAm segments, respectively. Upon heating to the LCST (35 °C), the double responsive polymers could form nanoparticles with chitosan shells and PNIPAAm cores.…”

Pharmakotherapie mittels Nanomedizin

“…So unterscheidet sich zum Beispiel entzündetes von gesundem Ge webe unter anderem durch einen nied rigeren pHWert, eine erhöhte Tempera tur oder eine erhöhte Gefäßpermeabilität [38]. Diese Eigenschaften kann man sich zum Beispiel beim "Targeting" mit Tem peratur und pHsensitiven Nanoparti keln zunutze machen [39,40].…”

“…In Verbindung mit Polymeren, die andere Bedingungen für eine Konformationsänderung aufweisen, können so definierte Freisetzungseigen schaften arrangiert werden. Aufgrund der Multivalenz des umgebenden Polymerge rüstes werden sowohl eine Temperatur als auch pHEmpfindlichkeit der Freiset zungssysteme beobachtet [40,43] Unter Berücksichtung dieser Aspekte und der anfangs erwähnten steigenden Zahl an Tumorerkrankungen weist der vorhandene Markt ein sehr großes Po tenzial auf. Hier wird die Nanotechno logie beziehungsweise die Nanomedizin gerade im DrugDeliveryBereich als ei ne der erfolgversprechendsten Anwen dungen der nächsten 20 Jahre angesehen.…”

Hybrid vesicles co-assembled from anionic graft copolymer and metal ions for controlled drug release

“…The sensitivity of vesicles was achieved usually by modifying the surfaces with temperature or pH-sensitive polymers, or by including ionizable lipids in the bilayers of vesicles. Poly(N-isopropylacrylamide) (PNIPAM), which exhibits a lower critical solution temperature (LCST) in water at about 32°C, is one of the most studied thermo-sensitive polymers to prepare smart materials [21,22]. As a result of containing weakly ionizable groups and exhibiting a reversible swelling-collapse transition when the net charge decreases, sodium alginate and other natural polyions are natural pH-sensitive polymers [23,24].…”