How does the addition of shape distinct gold nanoparticles influence on the conformational transition of poly(N-isopropylacrylamide)?

HYPOTHESIS: The subject of nanomaterials has created immense interest and expectations in the field of science and nanotechnology. Plentiful aspects proposed by gold nanoparticles (AuNPs) and their capability to affect macromolecular transition is the main driving force to execute the current study. A thermo-responsive polymer poly(N-isopropylacrylamide) (pNIPAM) is studied in presence of nanoparticles, particularly gold nanorods and nanospheres to elucidate completely the effect of their shape, surface area and structural morphology on the conformation of pNIPAM. EXPERIMENTS: In this respect, several biophysical techniques such as fluorescence spectroscopy, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) are utilized to examine the interaction of Au nanospheres/nanorods with pNIPAM. For a better understanding of Au nanoparticles morphology, transmission electron microscopy (TEM) is also employed. FINDINGS: Introducing gold nanoparticles with the polymeric solution promotes the polymer to stay in the coil conformation at a higher temperature than the LCST of aqueous pNIPAM. A shift of 2 and 25.5 °C in the LCST of pNIPAM is observed along with Au nanospheres and nanorods, respectively. The current study provides a better impact in the field of biomedical science specifically drug delivery and tissue engineering as the LCST approaches human body temperature.

The role of osmolytes in the temperature-triggered conformational transition of poly(N-vinylcaprolactam): an experimental and computational study.

Biomedical industries are widely exploring the use of thermo-responsive polymers (TRPs) in the advanced development of drug delivery and in many other pharmaceutical applications. There is a great need to investigate the use of less toxic and more (bio-)compatible TRPs employing several additives, which could modify the conformational transition behavior of TRPs in aqueous solution. To move forward in this aspect, we have chosen the less toxic bio-based polymer poly(N-vinylcaprolactam) (PVCL) and three different methylamine-based osmolytes, trimethylamine N-oxide (TMAO), betaine and sarcosine, in order to investigate their particular interactions with the polymer segments in PVCL and therefore the corresponding changes in the thermo-responsive conformational behavior. Several biophysical techniques, UV-visible spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS) and laser Raman spectroscopy, as well as classical computer simulation methods such as molecular dynamics are employed in the current work. All the studied methylamines are found to favor the hydrophobic collapse of the polymer thus stabilizing the globular state of PVCL. Sarcosine is observed to cause the maximum decrease in lower critical solution temperature (LCST) of PVCL followed by TMAO and then betaine. The differences observed in the LCST values of PVCL in the presence of these molecules can be attributed to the different polymer-osmolyte interactions. The less sterically hindered N atom in the case of sarcosine causes a significant difference in the phase transition temperature values of PVCL compared to betaine and TMAO, where the nitrogen atom is buried by three methyl groups attached to it.

Efficacy of several additives to modulate the phase behavior of biomedical polymers: A comprehensive and comparative outlook.

Several new classes of polymeric materials are being introduced with unique properties. Thermoresponsive polymers (TRPs) are one of the most fascinating and emerging class of biomaterials in biomedical research. The design of TRPs with good response to temperature and its ability to exhibit coil to globular transition behavior near to physiological temperature made them more promising materials in the field of biomaterials and biomedicines. Instead of numerous studies on TRPs, the mechanistic interplay among several additives and TRPs is still not understood clearly and completely. The lack of complete understanding of biomolecular interactions of various additives with TRPs is limiting their applications in interdisciplinary science as well as pharmaceutical industry. There is a great need to provide a collective and comprehensive information of various additives and their behavior on widely accepted biopolymers, TRPs such as poly(N-isopropylacrylamide) (PNIPAM), poly(vinyl methyl ether) (PVME), poly(N-vinylcaprolactum) (PVCL) and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG) in aqueous solution. Obviously, as the literature on the influence of various additives on TRPs is very vast, therefore we focus our review only on these four selected TRPs. Additives such as polyols, methylamines, surfactants and denaturants basically made the significant changes in water structure associated to polymer via their entropy variation which is the direct influence of their directly or indirectly binding abilities. Eventually, this review addresses a brief overview of the most recent literature of applications based phase behavior of four selected TRPs in response to external stimuli. The work enhances the knowledge for use of TRPs in the advanced development of drug delivery system and in many more pharmaceutical applications. These kinds of studies provide powerful impact in exploring the utility range of polymeric materials in various field of science.

Scrutinizing the effect of various nitrogen containing additives on the micellization behavior of a triblock copolymer.

HYPOTHESIS: PEG-PPG-PEG contains hydrophobic (PPG) as well as hydrophilic (PEG) blocks have gained popularity due to their different physiochemical properties that make them useful in several scientific areas and industrial applications such as detergency, stabilizers for dispersion, foaming and many more. Scientific communities reported that additives have ability to tune the micellization/demicellization tendency of PEG-PPG-PEG which we further extended by the use of several N-containing additives. Especially, chemists and biochemists are interested to extend the potential role of PEG-PPG-PEG copolymer in biomedical sensing applications, that is why triblock copolymer is chosen with various additives in the present study. EXPERIMENTS: The work reports the results obtained through different kinds of interactions induced among the poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) and additives containing different structural moieties. In order to tune micellization tendency of PEG-PPG-PEG, several additives such as trimethylamine-N-oxide (TMAO), betaine, sarcosine, guanidinium hydrochloride (GdnHCl) and urea are introduced in the current part of work and studied using UV-visible and fluorescence spectroscopy, dynamic light scattering (DLS), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy. FINDINGS: The methylamines facilitate the micellization to higher extent in comparison to that in aqueous PEG-PPG-PEG system, thereby decreasing the critical micellization temperature (CMT) values of PEG-PPG-PEG. Among studied methylamines, sarcosine has the highest efficacy in inducing the micellization followed by TMAO and betaine to the least extent. Direct interactions among polymeric segments and sarcosine is thought to be the main driving force for micellization of PEG-PPG-PEG. This is not possible for the case of betaine and TMAO due to the presence of the sterically hindered N atom. In contrast to these methylamines, GdnHCl and urea provided favorable binding sites for bridging interactions among polymer segments and thus lead to higher temperature values for CMT of PEG-PPG-PEG.

An efficient study to reach physiological temperature with poly(N-isopropylacrylamide) in presence of two differently behaving additives.

HYPOTHESIS: The new findings in the field of polymeric materials expanding their applications in improving the quality of health care are of primary concern. Undoubtedly, the alteration in surface properties of polymeric materials on addition of different additives may provide a step forward towards their better implications in many areas of science. In this regard, the interactions of poly(N-isopropylacrylamide) (PNIPAM) with two differently behaving additives may lead to a new method to carry the phase transition temperature of PNIPAM more near to body temperature so that it can be easily used in drug delivery through intravenous or oral insertion. EXPERIMENTS: Individually, the addition of sodium dodceylsulfate (SDS) and trimethylamine N-oxide (TMAO) is increasing and decreasing the lower critical solution temperature (LCST) of PNIPAM as compared to classical LCST of PNIPAM in aqueous solution, respectively. In the present study, we try to emphasis the role of mixed SDS and TMAO environment in varying ratios on the phase transition behaviour of PNIPAM. Many biophysical techniques are employed such as UV-visible spectroscopy, fluorescence spectroscopy and dynamic light scattering (DLS), Laser Raman spectroscopy technique and Field emission scanning electron Microscopy (FESEM) for this part of work. FINDINGS: The SDS is observed to form globules with PNIPAM segments and do not lead to turbidity of solution for the concentration greater than 10 µM. The negatively charged SDS bound PNIPAM globules that do not allow PNIPAM to associate, however; TMAO leads to turbid solution resulted from the hydrophobic association of PNIPAM. SDS is found to be very effective in increasing the LCST up to 62.8 °C even at very low (7.5 mM) concentration as compared to decreasing efficiency of TMAO where LCST reaches up to 29.4 °C for 0.75 M however, their mixture in specified concentration (1 mM SDS and 0.1 M TMAO) can bring the LCST of PNIPAM very near to body temperature (i.e. ∼36 °C) that is quiet promising for its use in target delivery engineering. TMAO ability to counteract the adverse effect of SDS is the main core reason in getting LCST near to body temperature.

An unexplored remarkable PNIPAM-osmolyte interaction study: An integrated experimental and simulation approach.

We investigate the aggregation and collapse of water soluble amphiphilic polymer, poly(N-isopropylacrylamide) (PNIPAM), in aqueous solution containing variable amount of trehalose, sucrose and sorbitol. The effect of these osmolytes on the coil to globular transition of the PNIPAM is studied by the use of comprehensive biophysical techniques like UV-visible spectroscopy, fluorescence spectroscopy, dynamic light scattering and Fourier transform infrared spectroscopy (FTIR). The polarization induced by these additives promotes the collapsed state of PNIPAM at much lower temperature as compared to the pure PNIPAM in aqueous solution. The decrease in the lower critical solution temperature (LCST) of the polymer with increase in the concentration of osmolyte is due to the significant changes in the interactions among polymer, osmolyte and water. The high affinity of these additives toward water destabilize the hydrated macromolecular structure via preferential interactions. To investigate the molecular mechanism behind the decrease in the LCST of the polymer in presence of the osmolytes, a molecular dynamics (MD) study was performed. The MD simulation has clearly shown the reduction in hydration shell of the polymer after interacting with the osmolyte. MD study revealed significant changes in polymer conformation because of osmolyte interaction and strongly supports the experimental observation of polymer phase transition at temperature lower than typical LCST. The driving force for concomitant sharp configurational transition has been attributed to the rupture of hydrogen bonds between water and polymer and to the hydrophobic association of the polymer. The results of the present study can be used in the bioresponsive smart PNIPAM-based devices as its LCST is close to body temperature. This study provides an alternative method to tune the LCST of the widely accepted model PNIPAM polymer.