Thermo PNIPAM

Kim et al. used the exchange reaction to synthesize cross-linked AuNP-PNIPAM core-shell hybrid structures, as well as a brush-type AuNP/PNIPAM hybrid through surface-initiated ATRP in an aqueous medium. The disulfide initiators, [BrC (CH3)2COO(CH2)iiS]2, were bound to AuNPs synthesized by citrate reduction. They have studied the effect of cross-linking on the thermo-responsiveness of the AuN / PNIPAM hybrids for potential use as a stimuli responsive optical device, such as surface plasmon resonance-based sensing materials [91]. 

Au NPs protected with a thermo-responsive polymer such as PNIPAM by the covalent grafting to technique with different end-functional PNIPAMs and various ratios between PNIPAM and HAuC14 has been studied. PNIPAM samples were synthesized through either conventional radical polymerization or living/controlled radical polymerization. With this approach, very small and quite monodisperse Au NPs are obtained with diameters ranging from 1.5 to 2.3 nm [94]. 

Qin et al. [229] produced a thermo-responsive PEO-fe-PNIPAM block copolymer that forms vesicles above the LCST of 32°C. The PEO-b-PNIPAm vesicles are shown to be stable at body temperature and to encapsulate both hydrophilic drugs (e.g., Doxorubicin) and hydrophobic molecules into their membranes (e.g., PKH 26). Temperature-controlled quick release of both types of compounds below 32°C was possible. 

Recently, Liu s group also reported the fabrication of thermoresponsive cross-linked hollow poly(A-isopropylacrylamide) (PNIPAM) nanocapsules with controlled shell thickness via the combination of surface-initiated atom transfer radical polymerization (ATRP) and click cross-linking. Cross-linked PNIPAM nanocapsules were fabricated by the click cross-linking of PNIPAM shell layer with a tri-functional molecule, l,l,l-fm(4-(2-propynyloxy) phenyl)ethane. Due to the thermo-responsiveness of PNIPAM, cross-linked PNIPAM nanocapsules exhibit thermo-induced collapse/swelling transitions that make it possible to classify them as nanogels. 

Due to its high stability, the membrane of polymersomes has low fluidity, which leads to a very limited ttansport through the membrane. Thus, in order to allow for transmembrane transport, specific efforts are necessary. One option is the use of responsive polymer blocks, which allow a switching of the block from hydrophilic to hydrophobic, or vice versa. This can be achieved with thermo-responsive poly(Af-isopropylacrylamide) (PNIPAM), pH-sensitive amino-functionalized methacryl derivatives (e.g., poly(diethylaminoethyl methacrylate) (PDEAEM)), or the redox-sensitive poly(propylene sulfide) (PPS). 

Figure 21 Schematic illustrations for pH- and thermo-induced supramolecular self-assembly of (PEO)(PDEAEMA)(PNIPAM) ABC miktoarm star terpolymers into two types of micellar aggregates possessing hybrid coronas in aqueous solution. Reprinted from Zhang, Y. Liu, H. Hu, J. et at.

Another attempt to incorporate PNIPAM segments into the ABA architecture has been completed through the RAFT mechanism. PDMA-PNIPAM-PDMA copolymers were synthesized at room temperature in water using a novel water-soluble trithiocarbonate RAFT agent. Thermo sensitive reversible micelles are obtained at temperatures above the LCST of PNIPAM by hydrophobic association showing that these triblocks are promising candidates for drug delivery applications. 

These precursor polymers lead to hydrophilic thermo-sensitive block copolymers, which form at room temperature (RT) transparent solutions which convert during heating into electrosterically stabilized PSS-PNIPAm, PAA-PNIPAm, PDADMAC-PNIPAm, and PDEAMEMA-PNIPAm block copolymer particles. 

The system MPEG53-fe-PNIPAMn3 (MPEG is PEO with a methyl endgroup) was studied by Pamies et al. [111]. SDS was used as surfactant component in this work too. Related to the thermo-responsive character of the PNIPAM block, this type of BCP exhibits an interesting self-assembly behavior. SDS has a strong influence on this behavior, and the Anally obtained structure depends on the temperature and the SDS concentration. The results are summarized by the authors... 

Although most polymers tend to accumulate at the fluid interface, reports involving the transfer of polymeric micelles (micellar shuttle) between two immiscible phases have been pubHshed. Poly(N-isopropylacrylamide) (PNIPAM), a thermally responsive polymer, is insoluble and can undergo a conformation change above its lower critical solution temperature of 32 ° C. The thermo reversible miceUization—demicellization process and micellar shuttle of PNIPAM-PEO diblock copolymer at a water-IL interface were investigated by dissipative particle dynamics (DPD) simulations (Soto-Figueroa et al, 2012). Simulation results confirm that the phase transfer behavior of polymeric micelles is controlled by the temperature effect that changes the diblock copolymer from hydrophilic to hydrophobic (as shown in Fig. 33). 

However, the development of in vivo applications for PNIPAM is limited by its non-biodegradability and the presence of amide moieties that reduce its biocompatibility. For this reason, other thermo-responsive polymers have been investigated in recent years. Poly(N-vinylcaprolactam) is a promising alternative. This polymer has a LCST between 35 and 38°C, again close to the temperature of the human body, and is characterized by high biocompatibility and low toxicity (Konak et al, 2007 Medeiros et al, 2010 Shtanko et al, 2003 Yanul et al, 2001). Additionally, amphiphilic copolymers such as Pluronics and Tetronics have been developed, based on copolymers of polyethylene oxide and polypropylene oxide. These copolymer systems exhibit a solution-gel transition at close to human body temperature that permits their application as injectable implants (Samchenko et ai,2011). 

Physical adsorption Block copolymers PNIPAM-b-poly(L-glutamic acid) Thermo-responsive glycomicelles pH-responsive nanogels from block copolymers with controlled structures Temperature and pH-responsive copolymers based on poly(ethylene oxide) and poly(methacrylic acid) Theato, 2008 Chen et al., 2009 Yusa et al., 2009 Jiang and Zhao, 2008... 

Purushotham and Ramanujan (2010) presented a case study in which iron oxide (Fej04) mNPs were coated with a thermo-sensitive polymer, PNIPAM, and used for simultaneous magnetic hyperthermia and controlled... 

Amphiphilic star-shaped copolymers with a cholic acid core comprising PCL tethered on the OH sites and linear PEO or PNIPAM tethered on the COOH site have been prepared by combination of ROP and COOH-NH2 coupling reaction (Scheme 19) [127, 129]. The polymerization of s-caprolactone in these cases was catalyzed by Sn(Oct)2. The star-shaped amphiphilic or thermo-responsive copolymers were studied to assess their micellization behavior and degradation rate, for potential use as smart drug-release systems. 

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