Stimuli Sensitive Polymers Types and Applications

Stimuli Sensitive Polymers Types and ApplicationsThe stimuli huffy polymers take away proved its applicability in forming hydro- gels 1, drug de experiencery2 and target specificity3. some(prenominal) stimuli irritable polymers occur in nature likeeg, chitosan, cellulose, xyloglucan and many of them are routinely synthesized like, poly(N-isopropylacrylamide) (PNIPAAm) and co-polymers of PNIPAAm4. Nature has designed entangled structures in repartee to various external stimuli. For example, the nano-composite structure of collagen fibrils in sea cucumber alters stiffness of its informal dermis5. This alteration of connective tissue is reversible, which acts as a defense mechanism6, 7.Capadona etal.,synthesized a chemo-responsive polymeric nano-composite structure, which mimics the solvent of collagen fibrils when overt to similar physiological conditions. This polymeric nano-composite is based on ethylene oxide-epichlorohydrin copolymer on to which rigid nanofiber ne 2rk of cellulose was assimilated 8. mental synthesis of cellulose whiskers, ethylene oxide-epichlorohydrin and polyvinyl acetate matrix polymer. Cellulose whiskers was isolated from tunicate cellulose pulp by sulfuric social disease hydrolysis9.Study of nanocompositeisbased on a rubber like ethylene oxideepichlorohydrin (11) copolymer (EO-EPI) into which arigid cellulose nanofiber network was assimilated 9.Naturally derived stimuli in the altogether polymers have intact properties like biocompatibility, efficient degradation of byproducts and specific biological moveions, these polymers have limitations like limited availability, jalopy to batch variation resulting in composition, poor mechanical strength as compa deprivation to synthetic stimuli sensitive polymers. Naturally derived stimuli sensitive polymers like chitosan, a polysaccharide, which is not stimuli sensitive but could be made stimuli sensitive by miscellanea with glycerophosphate, other examples are cellulose derivativ es like methyl cellulose, hydroxypropylmethyl cellulose10. A list of naturally derived stimuli sensitive polymers along with chemical substance structures is mention in table 1.1.1 Stimuli responsive polymersSynthetic polymers have proved in that respect applicability as therapeutic agent in drug delivery. These polymers showbetter pharmacokinetic property with greater ability for tissue targeting. The synthetic polymershows response when stimulated by external stimuli hence, they are called smart polymer or stimuli responsive polymer 15. The stimuli-responsive polymer works on the regulation of identification, evaluation of external signal and then by changing its structural conformation16.These stimuli are classified as physical (temperature, light, electrical field), chemical (pH,ion, tearingox)17, and biological responses.This results in change in a conformation, alteration in partition coefficient or solubility, drug release or more than one change at kindred time18.Physica l responsive polymersSome polymers respond to physical stimuli like temperature, light, electrical field, magnetic field,etc.Polymers which become non-water-soluble on heating, have lower critical solution temperature (LCST) like, PNIPAM 19, and those which become soluble on heating have upper critical solution temperature (UCST) like, poly (2-phenyl-2-oxazoline) (PPhOx) 20.Temperature sensitive polymersThermo-responsive polymers utilize bitty changein temperature to cause macroscopic alteration in polymer material 21. Various types of thermo-responsive fluorescent polymers like a) PNIPAAmb) PNIPAAm-fluorescent labeled c)PNIPAAm-co-butyl methacrylate-fluorescent labeled, a hydrophobic co-polymer butyl methacrylate (BMA) was used to lower LCST to a precise temperature d) PNIPAAm-co-DMAPAAm-fluorescent labeled (Figure. 2), N,N-dimethylaminopropylacrylamide(DMAPAAm) causes increase in LCST throughhydrophilization of polymeric chain,where synthesized, which shows thermo selective cell ular inspiration, enables determination of normal and pathological cell21. miniature sensitive polymersThe light sensitive polymers undergo photochromism, in which, an reversible chemical transformation occurs between two isomeric forms of same structure after preoccupation of light22. Absorption of light leads to photochromism which results alteration in submergence spectra23. Pericyclic reaction, dissociation process, cis-trans isomerization, electron transfer(oxidation-reduction) and intramolecular hydrogen transfer or pigeonholing transfer are the mechanisms involved in it24. A reversible contraction and expansions in shape and volumes of photochromic light crystal elastomers (LCE) in response to light stimulation.These LCE filmscontainpoly(siloxane) as main chain and cross-linkedchromo-thermicazobenzene, this film was placed on solid support, which helps maintaining temperature to 85c.1.1.2 chemic responsive polymersPolymer which exhibits change in configuration or which r esponds to chemical stimuli like pH, ion and other stimuli are know as chemical responsive polymers like, poly(methylacrylate)25.1.1.2.1 pH responsive polymerspH responsive polymers contain pendant antiphonal groups which when are cross-linked with other polymer forming hydrogel shows response to stimulus like pH 25. In recent years, muchwork has been exploredon co-polymerization of pH and temperature sensitive monomers17, 26. Graft co-polymers were synthesized to show temperature and pH sensitivity. A side chain temperature sensitive polymer (Figure 4.), the amino terminal ofNIPAAm was graftedon a carboxyl group of pH sensitive backbone polymer, like poly(acetic back breaker) (PAAc), in the presence of dicyclohexylcarbodiimide (DCC) and methanol by utilise trades union method26.Stimuli sensitive polymer- spot conjugationDyes or indicatorsare used to sense or react to particular stimuli like pH and temperature 27. Some indicator changes color in H+ and OH ion solution due to whic h they are use as pH sensitive dyes and those which changes color by deflection in temperature are use as temperature sensitive dyes 27. A list of thermo-chromic polymer-dye conjugations are shown in table 2.The novel chromogenic polymer gel network was synthesized by alloy poly(alkoxy) derivative with bromothymol blue, which yields transparent green gel (Figure 5.), at 33c, green gel turns intolight yellow gel with gradual increase in temperature29. In table 2, list of different chromogenic polymer gel networks arementioned.Poly(alkoxy) gel network was used to form interlinking with other dyes like, nitrazin yellow, where, color of gel network changes from blue to green. Similarly, for chlorophenol red, where color changes from red to yellow PVA-borax-cresol, phenol substituted dye (cresol) was conjugated with PVA-borax complex to obtain thermochromic hydrogel. Other example, PVA-borax-2,6-diphenyl-4-(2,4,6-triphenylpyridinio)phenolate (DTPP) forms reversible thermochromic hydro gel.Such brass shows color change and increase in absorption by a gradual increase of temperature. The absorption spectrum of DTPP explains dependency of absorbance on temperature causes bathochromic shift of absorption maximum 28.InBorax-PVA-DTPP network,DTPP was embedded in PVA-borax gel matrix, boric acid is cross linked to PVA polymer that is, borate ions reacts with hydroxyl group present on PVA to form monodiol-borate complex and didiol-borate complex 30.Another example of gel containing dye composed of two polymers (PVA and polyether) includes addition of zwitterionicsurfactant, which is a dipolar surfactant,was selected to avoid strong ionic interaction with anionic dye. This surfactant, like, sulfobetain forms aggregates above its critical micelle concentration therefore, it can determine U.V-absorption spectra of a water soluble dye like phenol red as shown in 31.The dye can also be conjugated with dendrimer to enhance imaging applications and for metal ion probing32. Fo r example, generation 5 poly(amidoamine) G5(PAMAM) dendrimercontaining 128 clear sites which can incorporate 0 to7 dyes like, 6-carboxytetramethylrhodamine succinimdyl ester (TAMRA), fluorescein. Acetylation yields complete conjugate of dendrimer and dye 33.nano sized stimuli sensitive polymers have been proved to show response to external signaling 34. pH sensitive trunk was prepared by the cabal of two modified pH sensitive indicator dyes like, N-fluoresceinylacrylamide (FA), and N-acrylamide-N-rhodamine B thiourea (Rh B) (Figure. 11).These two functional monomeric dyes were copolymerized with acrylamide and methylenebis(acrylamide) in w/o micro-emulsion to form dye conjugated poly(acrylamide nano elements 35. Synthesis ofN-fluoresceinylacrylamide- N-acrylamide-N-rhodamine B thiourea (FA-Rh B)copolymerized nanoparticles. The two functional monomeric dyes FA and Rh Bwere co-polymerized with acrylamide and methylenebis acrylamide in w/o micro-emulsion 35.Fluorescence emission spe ctra of polyacrylamide nanoparticle conjugated with fluorescein and rhodamine dye. The fluorescence emission intensity of Rh B be unchanged with increasing pH whereas that of FA increases.An amine functionalized RAFT co-polymer poly N-(2-hydroxypropyl) methacrylamide-bN-3-(dimethylamino)propyl methacrylate poly (HPMA258b-DMAPMA13) was labeled by fluorescent dye like, 6-(fluorescein-5-carboxamido)hexanoic acid, succinimidyl ester (5-SFX) using anhydrous DMF along with triethanolamine which catalysis the reaction 36. The primary amine of poly(HPMA258-b-DMAPMA13) is more reactive than tertiary thiol group this allows conjugation of 5-SFX with poly(HPMA258-b-DMAPMA13).-cyclodextrinis cyclic oligosaccharide 37, which has been proved for large number of applications like, increasing solubility 38, detection of compounds 39, immobilization of nephrotoxic compounds 40, drug release 41 etc. Some dyes were conjugated in complexing agent like an azo dye inside -cyclodextrincavity.Azo dye lik e methyl red indicator shows color change from yellow to red as pH decreases, this is because of the protonation of azo group (Figure 14.). Methyl red (MR) shows yellow color when complexes with -CD even in acidic pH 4.The complex was formed in dimethylacetoamide by using an condensing agent like, dicyclohexylcarbodiimide, it becomes multipurpose in detection of neutral species which go away act as guest inside MR--CD complex and will replace MR, which changes its color to red 42.Role of polymer-dye conjugation in cellular uptakeCellular uptake consist of endocytosis process in which extracellular compounds are captured by plasma membrane forming vesicles. Along with endocytosis there are other methods like, receptor mediated pathway, phagocytosis and micro-pinocytosis43.The plasma membrane of a eukaryotic cell has a barrier which allows small and uncharged molecules to pass through it44.The nano sized polymers, despiteplasma membrane barrier, can irreversibly interact with lipid membraneby insertion of dangling side chains into the hydrophobic region of cell, which can be explained by molecular dynamics45.Polymer like 2-methcryloyloxyethyl phosphorylcholine (MPC) was copolymerized with n-butyl methacrylate (BMA) forming poly(MPC-co-BMA)46,thecovalentlylabeledrhodamine Btopoly(MPC-co-BMA) (rhoPMB)was synthesized using free radical polymerization method with perbutyl-ND as an initiator.RhoPMB30 was distributed inside live HepG2 cell (a human hepatocellular liver carcinoma cell line).Natural polymer is applicable in biomedical, environmental science and rural field like, hydrophobically modified glycol chitosan (HGC) that can form stable nanoparticles. HGC shows prolonged blood circulation period when the particle size is controlled. It accumulates selectively inside tumor cell when administered systemically 47 and applicable in delivering various therapeutic agents like, peptides, genes and small anticancer drugs 43.The polymer conjugate probes are applicabl e for penetration inside the membrane of tumor cell for treatment48, detection49 or diagnosis50, 51.Further study for the conjugation ofpolymer and pH sensitive dye to form a reusable system which will sense or exhibit color change at different pH ranges.