Responsive Stimuli-Sensitive Polymers

Easy to mold and modify the SEirface with cell adhesion ligands Increased patient compliance  

Maintain stability and therapeutic window of the bioactive(s) Simple manufacturing and formEilation  

Better nutrients transport to cells and products from cell  

The presence of ionizable group of polymer with corresponding pKa. Therefore, the proper selection between polyacid and polybase should be considered for the desired application. 

The incorporation of hydrophobic moieties into the polymer backbone and controlling their nature, extent and distribution. When hydrophobic interactions dominate, ionizable groups become neutral nunionized state and electrostatic repulsion forces disappear within the polymer network. More hydrophobic groups incorporation can offer a more condensed structure in the uncharged state and a more accused phase transition. 

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As a model to understand and to describe the processes during the response of a smart gel on changes of enviromnental properties, a two-step mechanism can be assumed (Fig. 8). In a first step, the stimulus which triggers the swelling/shrinking must permeate the gel. Heat transfer for temperature-sensitive polymers or mass transfer (ions, organic solvents) determine the rate of the first step. 

In the last two decades, the development of poljoners which change their structures and properties in response to environmental stimuli such as pH, temperature, and light has attracted a great deal of attention (1-3). Such polymers have been called smart polymers, intelligent polymers, stimulus-sensitive pol3uners, or responsive polymers. They have been used in many applications, ranging from bioactive agent delivery to separation (4,5). Various delivery systems based on the smart polymers have been proposed because of their... 

Due to the relative ease of control, temperature is one of the most widely used external stimuli for the synthesis of stimulus-responsive bmshes. In this case, thermoresponsive polymer bmshes from poly(N-isopropylacrylamide) (PNIPAM) are the most intensively studied responsive bmshes that display a lower critical solution temperature (LOST) in a suitable solvent. Below the critical point, the polymer chains interact preferentially with the solvent and adopt a swollen, extended conformation. Above the critical point, the polymer chains collapse as they become more solvophobic. Jayachandran et reported the synthesis of PNIPAM homopolymer and block copolymer brushes on the surface of latex particles by aqueous ATRP. Urey demonstrated that PNIPAM brushes were sensitive to temperature and salt concentration. Zhu et synthesized Au-NPs stabilized with thiol-terminated PNIPAM via the grafting to approach. These thermosensitive Au-NPs exhibit a sharp, reversible, dear opaque transition in solution between 25 and 30 °C. Shan et al. prepared PNIPAM-coated Au-NPs using both grafting to and graft from approaches. Lv et al. prepared dual-sensitive polymer by reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide from trithiocarbonate groups linked to dextran and sucdnoylation of dextran after polymerization. Such dextran-based dual-sensitive polymer is employed to endow Au-NPs with stability and pH and temperature sensitivity. 

If the liposomes in question are treated with the polymer after their formation, the polymer binds only to the outer surface of the liposomes. If the liposomes are formed from a lipid-polymer mixture, on the other hand, the polymer is present on both sides of the liposome membrane. Such liposomes respond even faster to temperature changes. The change of the liposome surface properties caused by the phase transition of stimulus-responsive polymers in also known to affect their interaction with cells. The phenomenon has been used in an attempt to develop a targeted drug delivery system. Liposomes modified with a pH-sensitive polymer, namely succinylated poly(glycidol), were shown to deliver the dye cacein more efficiently into cultured monkey kidney cells than nonmodified liposomes. ... 

Self-organization of amphiphilic (co)polymers has resulted in assemblies such as micelles, vesicles, fibers, helical superstructures, and macroscopic tubes [174, 175]. These nanoscale to macroscale morphologies are of interest in areas ranging from material science to biology [176]. Stimuli-responsive versions of these assemblies are likely to further enhance their scope as smart materials. Thermo- or pH-sensitive polymer micelles [177] and vesicles [178] have been reported in which the nature of the functionality at the corona changes in response to the stimulus. Some attention has been also paid to realize an environment-dependent switch from a micelle-type assembly with a hydrophilic corona to an inverted micelle-type assembly with a lipophilic corona [179]. 

Stimuli-Responsive (SR) materials, also called smart materials have been attracting great interest within scientific community in the last few decades [1-4], They possess uitique properties that have made this class of materials very promising for several applications in the field of nanoscience. In particular, the smart materials undergo changes in response to small external variations in enviroiunen-tal conditions or to physical or biochenfical stimuli. In addition, there are dual SR materials that simultaneously respond to more than one stimulus [5-7]. For instance, temperature-sensitive polymers may also respond to pH changes [8-11]. 

A sensor is a system that displays a readily detectable response in the presence of a specific analyte. Indeed, stimulus-responsive vesicles have been tailor-made to function as highly specific sensors. The overwhelming majority of vesicle-based sensors are based on a very simple type of amphiphile polydiacetylenes. These polymeric amphiphiles are easily formed from simple diacelylene amphiphiles by in situ photopolymerization of vesicles. If the vesicles are additionally equipped with ligand or receptor groups, the absorbance and fluorescence of the conjugated polymer backbone is highly sensitive to the presence of metal ions, anions, and small as well as large... 

It is worth stressing here that thermal sensitivity is a general phenomenon for polymers in solution the solubility of all polymers in any solvent depends on temperature. For that reason, Allan Hoffman defined intelligent stimuli-responsive polymers as polymers that respond to a small physical or chemical stimulus with large property changes [68-70]. The coil-globule transition is a typical polymer response to a change in its solution temperature. 

Smart polymers Smart polymers include those polymers that act in response to very little change in the surrounding environment or to external stimulus, and thus they are also called environmentally sensitive or stimuli-responsive polymers or intelligent polymers. The unique character which makes these polymers intelligent and smart is their capability to respond even to minor changes in the nearby environment. These responses on one hand are fast and microscopic and on the other hand are reversible, which further enhance the imique character of these polymers. The response can be visualized or measured in terms of change in shape, solubility, sol-gel transition, surface characteristics and formation of complicated assembly of molecules, etc. [12,13]. This class of polymers will be discussed in detail later in the chapter. 

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