Metal organic framework-based polymeric hydrogel: A promising drug delivery vehicle for the treatment of breast cancer.

The constraints associated with current cancer therapies have inspired scientists to develop advanced, precise, and safe drug delivery methods. These delivery systems boost treatment effectiveness, minimize harm to healthy cells, and combat cancer recurrence. To design advanced drug delivery vehicle with these character, in the present manuscript, we have designed a self-healing and injectable hybrid hydrogel through synergistically interacting metal organic framework, CuBTC with the poly(vinyl alcohol) (PVA). This hybrid hydrogel acts as a localized drug delivery system and was used to encapsulate and release the anticancer drug 5-Fluorouracil selectively at the targeted site in response to the physiological pH. The hydrogel was formed through transforming the gaussian coil like matrix of PVA-CuBTC into a three-dimensional network of hydrogel upon the addition of crosslinker; borax. The biocompatible character of the hydrogel was confirmed through cell viability test. The biocompatible hybrid hydrogel then was used to encapsulate and studied for the pH responsive release behavior of the anti-cancer drug, 5-FU. The in vitro cytotoxicity of the drug-loaded hydrogel was evaluated against MCF-7 and HeLa cells. The study confirms that the hybrid hydrogel is effective for targeted and sustained release of anticancer drugs at cancer sites.

Multifunctional Ionic Hydrogel-Based Transdermal Delivery of 5-Fluorouracil for the Breast Cancer Treatment.

Transdermal drug delivery systems (TDDS) are a promising and innovative approach for breast cancer treatment, offering advantages such as noninvasiveness, potential for localized and prolonged drug delivery while minimizing systemic side effects through avoiding first-pass metabolism. Utilizing the distinctive characteristics of hydrogels, such as their biocompatibility, versatility, and higher drug loading capabilities, in the present work, we prepared ionic hydrogels through synergistic interaction between ionic liquids (ILs), choline alanine ([Cho][Ala]), and choline proline ([Cho][Pro]) with oleic acid (OA). ILs used in the study are biocompatible and enhance the solubility of 5-fluorouracil (5-FU), whereas OA is a known chemical penetration enhancer. The concentration-dependent (OA) change in morphological aggregates, that is, from cylindrical micelles to worm-like micelles to hydrogels was formed with both ILs and was characterized by SANS measurement, whereas the interactions involved were confirmed by FTIR spectroscopy. The hydrogels have excellent mechanical properties, which studied by rheology and their morphology through FE-SEM analysis. The in vitro skin permeation study revealed that both hydrogels penetrated 255 times ([Cho][Ala]) and 250 times ([Cho][Pro]) more as compared to PBS after 48 h. Those ionic hydrogels exhibited the capability to change the lipid and keratin arrangements within the skin layer, thereby enhancing the transdermal permeation of the 5-FU. Both ionic hydrogels exhibit excellent biocompatibility with normal cell lines (L-132 cells) as well as cancerous cell lines (MCF-7 cells), demonstrating over 92% cell viability after 48 h in both cell lines. In vitro, the cytotoxicity of the 5-FU-loaded hydrogels was evaluated on MCF-7 and HeLa cell lines. These results indicate that the investigated biocompatible and nontoxic ionic hydrogels enable the transdermal delivery of hydrophilic drugs, making them a viable option for effectively treating breast cancer.

Structural Rearrangement Followed by Entrapment of Subnanometer Building Blocks of Iron Oxyhydroxide in Aqueous Iron Chloride Solutions.

Iron oxyhydroxide, a natural nanophase of iron found in the environment, plays a crucial role in regulating surface and groundwater composition. Recent research proposes that within the nonclassical prenucleation cluster growth model, subnanometer-sized clusters (olation clusters/Fe13 δ-Keggin oxolation clusters) might act as the prenucleation clusters (PNCs) of ferrihydrite or iron oxyhydroxide solid phase. However, these clusters are difficult to characterize as they are only observable momentarily in low-pH, high-Fe concentration solutions before agglomerating into extended solids, keeping the controversy over the true nature of the PNCs alive. In this study, we introduce large quantities of zinc acetate salt (ZA) into iron chloride solutions at the olation-oxolation boundary (3.6 mM Fe3+ at pH ∼2.6). Remarkably, this manipulation is found to alter the structural arrangement of these subnanometer clusters before blocking them in isolation for hours, even at pH 6, where extended iron oxyhydroxide phases typically precipitate. On the other hand, controlled addition of ZA allows partial unblocking, leading to anisotropic agglomeration into cylindrical rod-like structures. Experimental techniques such as synchrotron-based small-angle X-ray scattering, X-ray absorption spectroscopy, high-resolution transmission electron microscopy (TEM), and cryo-TEM, along with density functional theory (DFT) calculations, reveal the nature of the structural rearrangement and the crucial role of Zn2+ ions in cluster stabilization.

Additive-anchored thermoresponsive nanoscale self-assembly generation in normal and reverse Tetronics®.

Self-assembly of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers (BCPs) in the presence of different kinds of additives is investigated in an aqueous solution environment. Commercially available four-armed BCPs, namely Tetronics® (normal: T904 with EO as the terminal end block; and reverse: T90R4 with PO as the terminal end block), each with 40%EO, are used. The effect of various additives such as electrolytes (NaCl and Na2SO4), nonelectrolyte polyols (glucose and sorbitol), and ionic surfactants (viz. anionic-sodium dodecyl sulfate (SDS), cationic-dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecyldimethylammonium propane sulfonate (C12PS)) on these BCPs is examined to observe their influence on micellization behaviour. The presence of salts and polyols displayed interesting phase behaviour, i.e., the cloud point (CP) was decreased, the water structure was affected and the micelles were dehydrated by expelling water molecules, and thus they were likely to promote micelle formation/growth. In contrast, ionic surfactants in small amounts interacted with the BCPs and showed an increase in CPs thereby forming mixed micelles with increasing charges and decreasing micellar sizes, finally transforming to small surfactant-rich mixed micelles. Molecular interactions such as electrostatic and hydrogen bonding involved within the examined entities are put forth employing a computational simulation approach using the Gaussian 09 window for calculation along with the GaussView 5.0.9 programming software using the (DFT)/B3LYP method and 3-21G basis set. The hydrodynamic diameter (Dh) of the micelles is examined using dynamic light scattering (DLS), while the various micellar parameters inferring the shape/geometry are obtained using small-angle neutron scattering (SANS) by the best fitting of the structure factors. It is observed that 10 w/v% T904 remains as spherical micelles with some micellar growth under physiological conditions (37 °C), while 10 w/v% T90R4 remains as unimers and forms spherical micelles in the presence of additives at 37 °C. Furthermore, the additive-induced micellar systems are tested as developing nanovehicles for anticancer (curcumin, Cur) drug solubilization using UV-vis spectroscopy, which shows a prominent increase in absorbance with enhanced solubilization capacity. Additionally, the cytotoxic effect of Cur loaded on the BCP micelles in HeLa cells is studied through confocal microscopy by capturing fluorescence images that depict HeLa cell growth inhibition under the influence of additive-induced micellar systems.

Molecular insights into the aggregation and solubilizing behavior of biocompatible amphiphiles Gelucire® 48/16 and Tetronics® 1304 in aqueous media.

A comparative analysis of the micellar and solubilizing properties of two polyethylene glycol (PEG)-based amphiphilic biocompatible excipients: Gelucire® 48/16 (Ge 48/16) and Tetronics® 1304 (T1304), in the presence and absence of salt, was conducted. As there is a dearth of research in this area, the study aims to shed light on the behavior of these two nonionic surfactants and their potential as nanocarriers for solubilizing pharmaceuticals. Various techniques such as cloud point (CP), dynamic light scattering (DLS), small-angle neutron scattering (SANS), Fourier transform infrared spectroscopy (FT-IR), UV spectrophotometry, and high-performance liquid chromatography (HPLC) were employed. The solubility of quercetin (QCT), a flavonoid with anti-inflammatory, antioxidant, and anti-cancer properties, was evaluated and the interaction between QCT and the micellar system was examined. The analysis revealed the occurrence of strong interactions between QCT and surfactant molecules, resulting in enhanced solubility. It was observed that the micellar size and solubilizing ability were significantly improved in the presence of salt, while the CP decreased. Ge 48/16 exhibited superior performance, with a remarkable increase in the solubility of QCT in the presence of salt, suggesting its potential as an effective nanocarrier for a range of pharmaceutics, and yielding better therapeutic outcomes.

Role of Gemini Surfactants with Variable Spacers and SiO2 Nanoparticles in ct-DNA Compaction and Applications toward In Vitro/In Vivo Gene Delivery.

Compaction of calf thymus DNA (ct-DNA) by two cationic gemini surfactants, 12-4-12 and 12-8-12, in the absence and presence of negatively charged SiO2 nanoparticles (NPs) (∼100 nm) has been explored using various techniques. 12-8-12 having a longer hydrophobic spacer induces a greater extent of ct-DNA compaction than 12-4-12, which becomes more efficient with SiO2 NPs. While 50% ct-DNA compaction in the presence of SiO2 NPs occurs at ∼77 nM of 12-8-12 and ∼130 nM of 12-4-12, but a conventional counterpart surfactant, DTAB, does it at its concentration as high as ∼7 µM. Time-resolved fluorescence anisotropy measurements show changes in the rotational dynamics of a fluorescent probe, DAPI, and helix segments in the condensed DNA. Fluorescence lifetime data and ethidium bromide exclusion assays reveal the binding sites of surfactants to ct-DNA. 12-8-12 with SiO2 NPs has shown the highest cell viability (≥90%) and least cell death in the human embryonic kidney (HEK) 293 cell lines in contrast to the cell viability of ≤80% for DTAB. These results show that 12-8-12 with SiO2 NPs has the highest time and dose-dependent cytotoxicity compared to 12-8-12 and 12-4-12 in the murine breast cancer 4T1 cell line. Fluorescence microscopy and flow cytometry are performed for in vitro cellular uptake of YOYO-1-labeled ct-DNA with surfactants and SiO2 NPs using 4T1 cells after 3 and 6 h incubations. The in vivo tumor accumulation studies are carried out using a real-time in vivo imaging system after intravenous injection of the samples into 4T1 tumor-bearing mice. 12-8-12 with SiO2 has delivered the highest amount of ct-DNA in cells and tumors in a time-dependent manner. Thus, the application of a gemini surfactant with a hydrophobic spacer and SiO2 NPs in compacting and delivering ct-DNA to the tumor is proven, warranting its further exploration in nucleic acid therapy for cancer treatment.

Aggregation Behavior of Nitrilotriacetamide (NTAmide) Ligands in Thorium(IV) Extraction from Acidic Medium: Small-Angle Neutron Scattering, Fourier Transform Infrared, and Theoretical Studies.

Two tripodal amides obtained from nitrilotriacetic acid with n-butyl and n-octyl alkyl chains (HBNTA(LI) and HONTA(LII), respectively) were studied for the extraction of Th(IV) ions from nitric acid medium. The effect of the diluent medium, i.e., n-dodecane alone and a mixture of n-dodecane and 1-decanol, onto aggregate formation were investigated using small angle neutron scattering (SANS) studies. In addition, the influence of the ligand structure, nitric acid, and Th(IV) loading onto ligand aggregation and third-phase formation tendency was discussed.The LI/LII exist as monomers (aggregarte radius for LI: 6.0 Å; LII:7.4 Å) in the presence of 1-decanol, whereas LII forms dimers (aggregarte radius for LII:9.3 Å; LI does not dissolve in n-dodecane) in the absence of 1-decanol. The aggregation number increases for both the ligands after HNO3 and Th(IV) loading. The maximum organic concentration (0.050 ± 0.004 M) of Th(IV) was reached without third-phase formation for 0.1 M LI/LII dissolved in 20% isodecanol +80% n-dodecane. The interaction of 1-decanol with LII and HNO3/Th(IV) with amidic oxygens of LI/LII results in shift of carbonyl stretching frequency, as shown by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies. The structural and bonding information of the Th-LI/LII complex were derived from the density functional theoretical (DFT) studies. The molecular dynamics (MD) simulations suggested that the aggregation behavior of the ligand in the present system is governed by the population of hydrogen bonds by phase modifier around the ligand molecules. Although the theoretical studies suggested higher Gibbs free energy of complexation for Th4+ ions with LI than LII, the extraction was found to be higher with the latter, possibly due to the higher lipophilicity and solubility of the Th-LII aggregate in the nonpolar media.

Glucose-induced self-assembly and phase separation in hydrophilic triblock copolymers and the governing mechanism.

Poly(ethylene oxide, EO)-poly(propylene oxide, PO)-poly(ethylene oxide, EO)-based triblock copolymers (BCPs) with 80% hydrophilicity stay molecularly dissolved as Gaussian chains at ambient temperature, even at fairly high concentrations (>5 %w/v). This study presents the plausible micellization behaviour of such very-hydrophilic Pluronics® - F38, F68, F88, F98, and F108 - incited upon the addition of glucose at low concentrations and temperatures. The outcomes obtained from phase behaviour and scattering studies are described. At temperatures near to ambient temperature, these BCPs form micelles with a central core made of a PO block, surrounded by a corona of highly hydrated EO chains. The phase transitions in these hydrophilic Pluronics® in the presence of glucose are demonstrated via the dehydration of the copolymer coil, leading to a decrease in the I1/I3 ratio, as determined using fluorescence spectroscopy. The temperature-dependent cloud point (CP) showed a marked decrease with an increase in the PO molecular weight and also in the presence of glucose. The change in solution relative viscosity (ηrel) caused by glucose is due to the enhanced dehydration of the EO block of the BCP amphiphile. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) investigations suggested that the dimensions of the hydrophobic core increase during the dehydration of the EO-PO blocks upon a temperature increase or after adding varying concentrations of glucose, thereby resulting in a micellar shape transition. It has been observed that added glucose influences the phase behaviour of BCPs in an analogous way to the influence of temperature. Also, plausible interactions between the EO-PO blocks and glucose were suggested based on the evaluated optimized descriptors obtained from a computational simulation approach. In addition, the core-shell blended micelles obtained using these BCPs are successfully utilized for drug (curcumin, Cur) solubilization based on the observed peak intensities from UV-visible spectroscopy. The loading of Cur into glucose-containing and glucose-free hydrophilic Pluronic® micelles shows how the radius of the micellar core (Rc) increases in the presence of glucose, thereby indicating Cur solubility enhancement for the Pluronic® micelles. Various kinetics models were employed, demonstrating a drug release profile that enables this approach to be used as an ideal platform for drug delivery.

Micellar assembly leading to structural growth/transition in normal and reverse Tetronics® in single and mixed solution environment.

This study scrutinizes the self-association of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers as normal Tetronic® (T904) and reverse Tetronic® R (T90R4) with varying molecular characteristics and different hydrophilic-hydrophobic ratios in an aqueous solution environment. These thermo-responsive solutions appear clear, transparent or bluish up to 10%w/v, which anticipated the probable transition of unimers to spherical or ellipsoidal micelles which is complemented by scattering experiments. In a single-solution environment, 10%w/v T904 formed star-shaped micelles at ambient temperature and exhibited a micellar growth/transition with temperature ageing. While 10%w/v T90R4 exists as unimers or a Gaussian coil over a wide range of temperature. Very interestingly, close to the cloud point (CP) flower-shaped spherical and ellipsoidal micelles were formed. A similar proposed micellar scheme was also examined for mixed systems T904 : T90R4 in varying ratios (1 : 0, 3 : 1, 1 : 1, 1 : 3 and 0 : 1) giving an account to the solution behavior of the mixtures. An amalgamation of dynamic light scattering (DLS) and small-angle neutron scattering (SANS) techniques achieved the thorough extraction of the structural parameters of the micellar system. The hydrodynamic diameter (Dh) of the micelles with temperature variation was evaluated from dynamic light scattering (DLS) while the structure factor of the micelles was found by employing small-angle neutron scattering (SANS). Furthermore, the single and mixed micellar systems were quantitatively and qualitatively examined for anticancer drug solubilization using UV-vis spectroscopy for their superior use as potential nanocargos.

Multimodal Applications of Zinc Gallate-Based Persistent Luminescent Nanoparticles in Cancer Treatment: Tumor Margining, Diagnosis, and Boron Neutron Capture Therapy.

On the basis of the boron neutron capture therapy (BNCT) modality, we have designed and synthesized a zinc gallate (ZnGa2O4)-based nanoformulation for developing an innovative theranostic approach for cancer treatment. Initially, the (ZnGa1.995Cr0.005O4 or ZnGa2O4:(0.5%)Cr persistent luminescence nanoparticles (PLNPs) embedded on silica matrix were synthesized. Their surface functionalization was performed using organic synthesis strategies to attach the amine functional moieties which were further coupled with poly(vicinal diol). These diols were helpful for conjugation with 10B(OH)3, which subsequently served to couple with an in-house-synthesized variant of pH-(low)-insertion peptide (pHLIP) finally giving a tumor-targeting nanoformulation. Most importantly, the polymeric diols helped in conjugation of a substantial number of 10B to provide the therapeutic dose required for effective BNCT. This nanoformulation internalized substantially (∼80%) to WEHI-164 cancer cells within 6 h. Tumor homing studies indicated that the accumulation of this formulation at the acidic tumor site was within 2 h. The in vitro evaluation of the formulation against WEHI-164 cancer cells followed by neutron irradiation revealed its potent cytotoxicity with IC50 ∼ 25 µM. In the case of studies on animal models, the melanoma-induced C57BL/6 and fibrosarcoma-induced BALB/c mice were treated with formulations through intratumoral and intravenous injections, respectively, followed by neutron irradiation, leading to a significant killing of the cancer cells, which was evidenced by a reduction in tumor volume (75-80%) as compared with a control tumor. Furthermore, the histopathological studies confirmed a damaging effect only on tumor cells, while there was no sign of damage to the vital organs in treated mice as well as in controls.

Formulation, Solubilization, and In Vitro Characterization of Quercetin-Incorporated Mixed Micelles of PEO-PPO-PEO Block Copolymers.

Quercetin (QCN) is a plant polyphenol with a variety of medicinal effects. Poor water solubility, on the other hand, restricts its therapeutic effectiveness. The purpose of this study was to develop mixed micellar systems using two biocompatible amphiphilic PEO-PPO-PEO triblock copolymers, Pluronic P123 (EO20-PO70-EO20) and Pluronic F88 (EO104-PO39-EO104), in order to enhance the aqueous solubility and oral bioavailability of QCN drug. The critical micelle concentrations (CMCs) of mixed P123/F88 micellar solutions were investigated using UV-visible spectroscopy with pyrene as a probe. Mixed P123/F88 micelles have low CMCs, indicating that they have a stable micelle structure even when diluted. The solubility of QCN in aqueous mixed P123/F88 micellar solutions at different temperatures was investigated to better understand drug entrapment. The QCN solubility increased with increasing temperature in the mixed P123/F88 micellar system. The QCN-incorporated mixed P123/F88 micelles were prepared using the thin-film hydration method and were well characterized in terms of size and morphology, compatibility, in vitro release and antioxidant profile. In addition, the cell proliferation activity of the mixed micelles was evaluated in the MCF-7 cell line. The QCN-incorporated mixed P123/F88 micelles had a small particle size (< 25 nm) and a negative zeta potential with a spherical shape. The in vitro release behaviour of QCN from a mixed P123/F88 micellar system was slower and more sustained at physiological conditions. The oxidation resistance of QCN-incorporating mixed P123/F88 micelles was shown to be considerably higher than that of pure QCN. An in vitro cell proliferation study revealed that QCN-incorporated mixed micells were effective in inhibiting tumour cell growth. In conclusion, the QCN-incorporated mixed P123/F88 micelle may be a promising approach to increase QCN oral bioavailability, antioxidant activity, and cell viability.

Interaction of a bovine serum albumin (BSA) protein with mixed anionic-cationic surfactants and the resultant structure.

The interaction of a bovine serum albumin (BSA) protein with the mixture of anionic sodium dodecyl sulfate (SDS) and cationic dodecyltrimethylammonium bromide (DTAB) has been investigated by small-angle neutron scattering (SANS) and dynamic light scattering (DLS). Both SDS and DTAB as individuals interact electrostatically as well as hydrophobically with BSA and form connected protein-decorated micelle like complexes in the aqueous solution, in which the well-defined surfactant micelles are organized along the randomly distributed unfolded polypeptide chain of the protein. The protein-surfactant interaction has been tuned by adding different molar mixtures of SDS and DTAB in BSA aqueous solution. It is found that a lower molar fraction of either surfactant in the protein-mixed surfactant complexes results in the formation of a connected protein-decorated micelle structure similar to those of pure surfactants. As the molar fraction of one of the surfactants in the mixture approaches the equimolar fraction, the structure formed by the protein-mixed surfactant is very different from the connected protein-decorated micelle like structure. Different microstructures of BSA-mixed surfactant complexes are formed, mostly governed by the structure of mixed surfactants arising from the strong electrostatic interaction of oppositely charged components. In this case, unfolded proteins wrap the structures of mixed surfactants around their surface. Along with the connected protein-decorated micelle like structure, rod-like and bilayer vesicles of protein-surfactant complexes are formed at different molar fractions of mixed surfactants.

Mixed Poloxamer Nanomicelles for the Anticonvulsant Lamotrigine Drug: Solubility, Micellar Characterization, and In-Vitro Release Studies.

Recently the applications of Poloxamers in drug development is promising as it facilitated the drug molecule for delivering to the correct place, at the correct time and in the correct amount. Poloxamers can form nanomicelles to encapsulate hydrophobic drugs in order to increase solubility, stability and facilitate delivery at target. In this context, the solubilization of anticonvulsant lamotrigine (LMN) drug in a chain of Poloxamers containing different polyethylene oxide and polypropylene oxide noieties were examined. The results showed better solubilization of LMN in Poloxamers contain low CMTs while poor with Poloxamers having high CMTs. Systematic investigation of two mixed Poloxamer nanomicelles (P407:P403 and P407:P105) for LMN bioavailability at body temperature (37 °C) were investigated. The solubility of LMN was enhanced in mixed P407:P403 nanomicelles with the amount of P403 and reduced in mixed P407:P105 nanomicelles with the amount of P105. LMN encapsulated mixed Poloxamer nanomicelles were found spherical in shape with ~25 nm Dh sizes. The In-Vitro release profiles of mixed Poloxamer nanomicelles demonstrated the biphasic model with initial burst release and then slowly release of LMN. Better biocompatibility of LMN in the mixed P407:P403 nanomicelles was confirmed with stability data. The results of this work were proven the mixed P407:P403 nanomicelles as efficient nanocarriers for LMN.

Self-Association in EO-BO-EO Triblock Copolymers as a Nanocarrier Template for Sustainable Release of Anticancer Drugs.

Ethylene oxide (EO)-butylene oxide (BO)-ethylene oxide (EO)-based triblock copolymers with varying hydrophilic-hydrophobic ratios in arrangement, generally referred to as EBE, were scrutinized in an aqueous environment. Various self-associative (micellization) physicochemical properties of these EBEs were examined at different temperatures unified with a quantum chemical study. The salting-out effect on 5%w/v EBE was examined by observing their aqueous solution behavior where the clear transparent solution/turbidity suggested the probable presence of spherical or ellipsoidal micelles, which was confirmed from the scattering outline. The hydrodynamic radius (Dh) of the formed micellar geometry as a function of temperature and electrolyte (2 M NaCl) was inspected from dynamic light scattering and further supported by small-angle neutron scattering, where the Q-range prototype and scattering parameters were evaluated by the best fitting of the structure factor. Furthermore, these micelles were employed as potential nanocarriers for anticancer (curcumin and quercetin) drugs, where its release profile at a particular time interval was estimated using UV-vis spectroscopy. Different kinetic models were employed to fit the release profile data that enabled this study to act as an ideal platform for drug delivery. Also, the plausible interactions between EO-BO-EO blocks and the anticancer drugs were inferred from the evaluated computational descriptors.

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells.

This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14-20 nm) which remained stable against temperature (ca. 25-45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π-π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.

Colloidal stability of graphene oxide nanosheets in association with triblock copolymers: A neutron scattering analysis.

This study investigates stabilization of graphene oxide (GO) nanosheets in polyethylene oxide-polypropylene oxide (PEO-PPO) block copolymers (P103, P123 and F127). Changes in micellization of copolymers upon GO addition were monitored using dynamic light (DLS) and small angle neutron scattering (SANS). Structural developments at sheet surface were studied with two possibilities; (i) adsorption of PPO block over hydrophobic basal plane allowing the engagement of hydrophilic PEO with aqueous bulk, and (ii) adsorption of micelles mediated via carboxylated groups. Insignificant changes in micellar parameters for P123 and P127 were indicative of their inferior interaction with GO. On the other hand, P103 micelles exhibited high affinity for sheets, noticeable as emergence of mass fractals and more than two-fold enhancement in micelle number density. The latter allowed coverage of entire surface with P103 micelles. Existence of mass fractals was verified by extracting the form and structure factors from the fitted SANS data. Spectroscopic and thermogravimetric analyses illustrated non-covalent adsorption of copolymer aggregates. It was interesting to note that the dispersion remained stable against protein and electrolyte addition. A comprehensive understanding on colloidal stability can be valuable for drug delivery applications of GO sheets.

Nanodiamonds as a state-of-the-art material for enhancing the gamma radiation resistance properties of polymeric membranes.

We report, for the first time, the development of gamma radiation resistant polysulfone (Psf)-nanodiamond (ND) composite membranes with varying concentrations of NDs, ranging up to 2 wt% of Psf. Radiation stability of the synthesized membranes was tested up to a dose of 1000 kGy. To understand the structure-property correlationship of these membranes, multiple characterization techniques were used, including field-emission scanning electron microscopy, atomic force microscopy, drop shape analysis, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, gel permeation chromatography, positron annihilation spectroscopy, and small angle X-ray scattering. All the composite membranes exhibited enhanced radiation resistance properties, with 0.5% loading of NDs as the optimum. Compared to the radiation stability of Psf membranes up to a dose of 100 kGy, the optimum composite membranes are found to be stable up to a radiation dose of 500 kGy, owing to the unique surface chemistry of NDs and interfacial chemistry of Psf-ND composites. Experimental findings along with the Monte Carlo simulation studies confirmed a five times enhanced life-span of the composite membranes in an environment of the intermediate level radioactive waste, compared to the control Psf membrane.

Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro-inflammatory cytokines in human breast adenocarcinoma cells.

BACKGROUND: Curcumin is a natural derivative, which exhibits broad spectrum biological activities including anti-oxidant, anti-inflammatory, and anti-cancer. Since ancient times, it has been used for the treatment of various diseases. Many reports highlighted its potential as a chemopreventive and chemotherapeutic agent. Despite its imperative properties, the pharmacological application had been limited due to low solubility in the aqueous medium, limited tissue absorption, and rapid degradation at physiological pH. AIMS: Cytotoxicity of drugs and their undesirable side effects are major obstacles in the regimens of cancer therapy. Therefore, natural plant derivatives-based anti-cancer drug delivery systems are getting more attention as they are less toxic, safer, and effective. In the present study, Pluronic block copolymer encapsulated curcumin was developed as an improved curcumin delivery system with the aim to improve its efficacy and biological response against cancer cells. METHODS AND RESULTS: Pluronic micelles encapsulated curcumin was synthesized, and its characterization was done by particle size analysis, Fourier transform infrared spectroscopy, small-angle neutron scattering analysis, PXRD, and differential scanning calorimetry. Further, its biological activities were corroborated in cancer cells. Results indicate that Pluronic micelles encapsulated curcumin exemplify solubility and stability of curcumin in the aqueous medium. Biophysical characterization indicated that Pluronic F127 forms nanoparticle, and its micellar core radius was increased after incorporation of curcumin. Furthermore, biological studies show that Pluronic micelles encapsulated curcumin inhibits cell proliferation, improves cellular uptake of curcumin, arrests the cell cycle in G0/G1 phase, and inhibits the activation of NF-kB and release of pro-inflammatory cytokines to manifest apoptotic cell death rather than necrotic. This formulation was non-toxic to normal cells. CONCLUSION: This study suggests that Pluronic micelles encapsulated curcumin is stable that can effectively inhibit cell proliferation and release of pro-inflammatory cytokines in cancer cells as compared with the free curcumin. This approach could be applied to improve the therapeutic index of anti-cancer agents.

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery.

In two ABA type amphiphilic block copolymers (P1, P2), the hydrophobic B block consists of a bioreducible segmented poly(disulfide) (PDS), while poly-N-isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether-methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively, leading to the formation of polymersome and micelle, owing to the difference in the packing parameters. Both exhibit comparable doxorubicin (Dox) encapsulation efficiency, but glutathione (GSH) triggered release appears much faster from the polymersome than micelle owing to the complete degradation of the PDS segment in polymersome morphology unlike in micelle. Dox-loaded polymers (P1-Dox and P2-Dox) exhibit minimum toxicity to normal cells like C2C12. By contrast, P1-Dox shows excellent killing efficiency to the HeLa cells (cancer cell) (in which the GSH concentration is significantly higher). However, P2-Dox reveals a rather poor activity even to HeLa cells. Fluorescence microscopy studies show comparable cellular uptake of P1-Dox and P2-Dox. But the polymersome entrapped dye escapes fast from the cargo and reach the nucleus, while the drug-loaded micelle remains trapped in the perinuclear zone explaining the significant difference in the drug delivery performance of polymersome and micelle.

Biodegradable toughened nanohybrid shape memory polymer for smart biomedical applications.

A polyurethane nanohybrid has been prepared through the in situ polymerization of an aliphatic diisocyanate, ester polyol and a chain extender in the presence of two-dimensional platelets. Polymerization within the platelet galleries helps to intercalate, generate diverse nanostructure and improve the nano to macro scale self-assembly, which leads to a significant enhancement in the toughness and thermal stability of the nanohybrid in comparison to pure polyurethane. The extensive interactions, the reason for property enhancement, between nanoplatelets and polymer chains are revealed through spectroscopic measurements and thermal studies. The nanohybrid exhibits significant improvement in the shape memory phenomena (91% recovery) at the physiological temperature, which makes it suitable for many biomedical applications. The structural alteration, studied through temperature dependent small angle neutron scattering and X-ray diffraction, along with unique crystallization behavior have extensively revealed the special shape memory behavior of this nanohybrid and facilitated the understanding of the molecular flipping in the presence of nanoplatelets. Cell line studies and subsequent imaging testify that this nanohybrid is a superior biomaterial that is suitable for use in the biomedical arena. In vivo studies on albino rats exhibit the potential of the shape memory effect of the nanohybrid as a self-tightening suture in keyhole surgery by appropriately closing the lips of the wound through the recovery of the programmed shape at physiological temperature with faster healing of the wound and without the formation of any scar. Further, the improved biodegradable nature along with the rapid self-expanding ability of the nanohybrid at 37 °C make it appropriate for many biomedical applications including a self-expanding stent for occlusion recovery due to its tough and flexible nature.