Dual pH Research Articles

Dual pH and thermoresponsive alternating polyampholytes in alcohol/water solvent mixtures

Polyampholytes consist of alternating opposite charges were synthesized by alternating RAFT (co)polymerization of cationic and anionic monomers and their pH dependent thermoresponsive behavior in water and alcohol/water solvent mixtures is reported.

Pillar[5]arene-based, dual pH and enzyme responsive supramolecular vesicles for targeted antibiotic delivery against intracellular MRSA.

A rationally designed mannosylated amphiphilic pillar[5]arene (Man@AP5) self-assembles into supramolecular vesicles with encapsulated vancomycin (Man@AP5-Van), which target macrophages, respond to both acid and cathepsin B, and release vancomycin (Van) rapidly inside macrophages. Man@AP5-Van significantly increases the intracellular concentration of Van, enhancing its antibacterial efficacy against intracellular MRSA.

Palladium nanoparticles-anchored dual-responsive SBA-15-PNIPAM/PMAA nanoreactor: a novel heterogeneous catalyst for a green Suzuki-Miyaura cross-coupling reaction.

To develop a sustainable and cost-effective catalyst for cross-coupling reactions, dual (temperature and pH)-responsive poly(N-isopropyl acrylamide-co-methacrylic acid) (PNIPAM/PMAA) functionalised SBA-15 was synthesised via free radical polymerisation using potassium persulfate as an initiator and decorated with palladium nanoparticles (PdNPs-SBA-15-PNIPAM/PMAA). The X-ray photoelectron spectroscopic analysis revealed that the Pd content in the zero oxidation state of the catalyst was 1.21 wt%. The dynamic light scattering studies showed that the catalyst exhibited swelling behaviours at low temperatures (<32 °C) and high pH (>4), but exhibited deswelling behaviours at high temperatures (>32 °C) and low pH (<4). To examine the performance of the catalyst, Suzuki–Miyaura cross-coupling (SMC) reaction was conducted under batch reaction conditions. The reaction conditions were optimised with various parameters using phenylboronic acid and bromobenzene as the model substrates. High conversions (>90%) were realized for the room-temperature SMC reaction in an aqueous medium for various substituted aryl halides, while the conversion was low at relatively high temperatures (>32 °C). The conversion was dependent on the different electronic effects between the electron-releasing and electron-withdrawing groups of the aryl halides. After the experiment, the catalyst was successfully recovered without any loss of heterogeneity and could be reused at least up to the fifth cycle.

Aqueous-based electrospun P(NIPAAm-co-AAc)/RSF medicated fibrous mats for dual temperature- and pH-responsive drug controlled release.

This paper presents a green method for fabricating dual temperature- and pH-responsive electrospun fibrous mats from an aqueous-based blend poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) and regenerated silk fibroin (RSF) by employing electrospinning technique. P(NIPAAm-co-AAc) was synthesized by free radical solution polymerization and its low critical solution temperature (LCST) was in the physiological range (38.8 °C). The P(NIPAAm-co-AAc)/RSF fibers were prepared by electrospinning technology in the presence of the crosslinking agents (EDC·HCl and NHS) with water as solvent. After in situ crosslinking and water-annealing process, the water-stable composite fibrous mats were obtained. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to analyze the crosslinking process. Temperature and pH dual stimuli-responsive swelling-shrinking behavior of the fibrous mats were observed when the temperature was below and above the LCST of the copolymer at different pHs. In addition, rhodamine B-loaded the fibrous mats also showed dual temperature and pH controlled release behavior, demonstrating the potential use of the fibrous mats for “smart” controlled drug delivery applications.

Functionalization of Si-C Using TEOS (Tetra Ethyl Ortho Silica) as Precursor and Organic Catalyst

Silica network was tailored configuring siloxane (Si-O-Si) and silanol (Si-OH) groups which are essential to produce porous-structured materials. As silanols are hydrophilic, react with water to form fouling. This research address to actualize strategy for synthesizing highly functionalized silica carbon (Si-C) using hybrid organic-inorganic structures as the primary method for improving hydro-stability by employing precursor TEOS and organic catalyst through a sol-gel process. Catalysis employs citric acid or citric acid-ammonia whereas carbon templated into silica network. The synthesis scheme involves: a) sol-gel process at 0°C and b) calcination. Silica sol dried into xerogels were prepared and calcined at 200°C and 250°C. Characterization of xerogels showed the infrared band areas of the organic groups to evaluate the thermal stability. For xerogel employed single (pH 5.5) and dual (pH 7.65) catalyst, infrared spectra showed mostly look similar Si-C area at similar wavelength. Silica xerogel is more effectively prepared from TEOS with one-step single acid catalyst including calcination.

Fission yeast Opy1 is an endogenous PI(4,5)P2 sensor that binds to the phosphatidylinositol 4-phosphate 5-kinase Its3.

Phosphoinositides (PIPs) are a dynamic family of lipids that execute diverse roles in cell biology. PIP levels are regulated by numerous enzymes, but our understanding of how these enzymes are controlled in space and time is incomplete. One role of the PIP phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is to anchor the cytokinetic ring (CR) to the plasma membrane (PM) in Schizosaccharomyces pombe While examining potential PI(4,5)P2-binding proteins for roles in CR anchoring, we identified the dual pleckstrin homology (PH) domain-containing protein Opy1. Although related proteins are implicated in PIP regulation, we found no role for S. pombe Opy1 in CR anchoring, which would be expected if it modulated PM PI(4,5)P2 levels. Our data indicate that although Opy1 senses PM PI(4,5)P2 levels and binds to the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, Opy1 does not regulate Its3 kinase activity or PM PI(4,5)P2 levels, a striking difference from its Saccharomyces cerevisiae homolog. However, overexpression of Opy1 resulted in cytokinesis defects, as might be expected if it sequestered PI(4,5)P2 Our results highlight the evolutionary divergence of dual PH domain-containing proteins and the need for caution when interpreting results based on their overexpression.This article has an associated First Person interview with the first author of the paper.

In vitro exploration of the synergistic effect of alternating magnetic field mediated thermo-chemotherapy with doxorubicin loaded dual pH- and thermo-responsive magnetic nanocomposite carriers.

Nanoparticle induced hyperthermia has been considered as a promising approach for cancer treatment for decades. The local heating ability and drug delivery potential highlight a diversified possibility in clinical application, therefore a variety of nanoparticles has been developed accordingly. However, currently, only a few of them are translated into the clinical stage indicating a 'medically underexplored nanoparticles' situation, which encourages their comprehensive biomedical exploration. This study presents a thorough biological evaluation of previous well-developed dual pH- and thermo-responsive magnetic doxorubicin-nanocarriers (MNC-DOX) in multiple cancer cell lines. The cytotoxicity of the nanocomposites has been determined by the MTT assay on primary cell lines. Histology and fluorescence microscopy imaging revealed the efficiency of cellular uptake of nanocarriers in different cell lines. The IC50 of MNC-DOX is significantly higher than that of free DOX without an alternating magnetic field (AMF), which implied the potential to lower the systemic cytotoxicity in clinical research. The concurrent thermo-chemotherapy generated by this platform has been successfully achieved under an AMF. Promising effective synergistic results have been demonstrated through in vitro study in multi-model cancer cell lines via both trypan blue exclusion and bioluminescence imaging methods. Furthermore, the two most used magnetic hyperthermia modalities, namely intracellular and extracellular treatments, have been compared on the same nanocarriers in all 3 cell lines, which showed that treatment after internalization is not required but preferable. These results lead to the conclusion that this dual responsive nanocarrier has extraordinary potential to serve as a novel broad-spectrum anticancer drug and worth pursuing for potential clinical applications.

Does the Reflux Symptom Index Predict Increased Pharyngeal Events on HEMII-pH Testing and Correlate with General Quality of Life?

To determine the ability of the reflux symptom index (RSI) to predict objective impedance and pH-probe testing, and to examine the relationship between disease-specific and general health status in patients diagnosed with laryngopharyngeal reflux (LPR). Adults presenting to a tertiary care academic center with a primary voice complaint completed the RSI and the Patient-Reported Outcomes Measurement Information System 10-item global health instrument (PROMIS). An RSI score ≥13 was considered abnormal. Objective testing for LPR was performed using hypopharyngeal-esophageal multichannel intraluminal impedance catheter with dual pH (HEMII-pH) testing; a positive test was defined as more than one pharyngeal impedance events over 24 hours. Spearman rho analyses were applied, and the sensitivity and specificity of the RSI to detect HEMII-pH findings were determined. One hundred four patients underwent HEMII-pH testing. Mean scores were 16.7 (95%CI 15.1-18.3) for RSI. Sixty-three (60.6%) patients were diagnosed with LPR by HEMII-pH testing. RSI scores were moderately correlated with PROMIS physical (Spearman rho 0.43, P < 0.0001), social (Spearman rho 0.33, P < 0.0001) and mental health (Spearman rho 0.33, P < 0.0001) scores. The RSI has a sensitivity and specificity of 66.7% and 31.7%, respectively, for detecting pharyngeal events on HEMII-pH testing. There is moderate sensitivity and lack of specificity of the RSI for detecting increased pharyngeal reflux events. Reflux-specific and general health status instruments are correlated. Further investigation could assess the diagnostic ability of RSI compared proximal reflux events on HEMII-pH, as well as whether health status instruments can be used to detect clinically meaningful change in the LPR population.

Preparation of macroporous polyvinyl alcohol formaldehyde based hydrogels and their dual thermo- and pH-responsive behavior

Dual thermo- and pH-responsive polymer hydrogels have broad potential applications due to their unique responsive behavior to environmental stimuliregulatedby more than one mechanism. Herein, the dual thermo- and pH-responsive polyvinyl alcohol formaldehyde (PVF) based hydrogels were successfully prepared via redox grafting polymerization by incorporating respectively poly(N-isopropylacrylamide) (PNIPAM) and poly(acrylic acid) (PAA) moieties onto PVF backbone. These hydrogels retain an interconnected macroporous structure with high porosity (~83.0%), facilitating rapid penetration and diffusion of water molecules. The sizes of pore and pore walls are in micrometer scale, significantly reducing the characteristic time of swelling or deswelling. Besides, these hydrogels possess the thermo-responsiveness even in high grafting percentage of PAA (60.8%), overcoming the inhibition effect of PAA moieties in a high content on thermal sensitivity of traditional poly(NIPAM-co-AA) copolymers. Their pH-responsiveness and excellent repeated absorption performance are determined by measuring the absorption capacities of hydrogels in water and different buffer solutions. Moreover, these hydrogels exhibit rapid deswelling kinetics on the minute time scale by detecting water retention in pH 3 buffer solution at 50 °C. In addition, the deswelling behavior leads to the noticeable changes of macroscopic dimensions of hydrogels; we anticipate potential applications in dual thermal and pH sensors.

Development of photo-magnetic drug delivery system by facile-designed dual stimuli-responsive modified biopolymeric chitosan capped nano-vesicle to improve efficiency in the anesthetic effect and its biological investigations

Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency anesthetic drug delivery system. Chitosan is a unique class of biomaterials that is widely used in medical devices. The surface engineering of ZnFe2O4 nanoparticles was performed by coating with chitosan using simple precipitation method. Then, multi-active anesthetic drug (Lidocaine) was loaded into nano-ferrite to form a drug delivery vehicle. The prepared drug-vesicle was characterized by using XRD, FTIR, SEM, XPS and TGA analysis. XRD analysis proved the face center cubic structure of zinc nanoferrite. The sustained delivery of Lidocaine (LDC) from CS coated nanoferrite (CS/ZnFe2O4) was stimulated by pH and temperature responsive characteristics of vesicles. The in vitro cytotoxicity of the CS/ZnFe2O4 particles towards fibroblast cells was analyzed by using MTT assay. The drug loaded CS/ZnFe2O4 particles exhibit high biocompatibility and sustained drug release in the physiological pH environment (4.8, 5.5 and 7.4) and temperature responsive (25 and 37 °C) of normal tissues and also drug loading efficiency was measured.

Effects of slough clearance rates post adult tonsillectomy in patients with laryngopharyngeal reflux disease

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Laryngopharyngeal reflux is known to be associated with multiple disease of the upper aero digestive tract and can cause serious injury to the mucosa long term.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Patients diagnosed with chronic tonsillitis and indicated for surgery were evaluated for laryngopharyngeal reflux using reflux symptom index score. When score greater than 13 was suggestive of laryngopharyngeal reflux (LPR) and counselled for 24 hours ambulatory dual probe pH monitoring. When the reflux event was 7 or more were diagnosed having LPR. Patients were divided into two groups Group A patients with chronic tonsillitis and without LPR and Group B patients with chronic tonsillitis and LPR. Postoperatively there slough percentage was calculated as 25%, 50%, 75%, 100% on the postoperative day (POD) 7, 14 and 21. Slough clearance rates were calculated as 100- slough percentage. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were 40 patients in Group A and 40 patients in Group B. The slough clearance rates of Group A were 46.3, 73.8 and 96.9 on post-operative days 7, 14, 21 respectively. The slough clearance rates of Group B were 30.1, 57.6, 90.1 on POD 7, 14, 21 respectively. The p values comparing slough clearance rates showed 0.00, 0.002, 0.013 on POD 7, 14, 21 which was statistically significant. Group B with laryngopharyngeal reflux had delayed healing than Group A.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Laryngopharyngeal reflux seems to adversely affect healing and complication following tonsillectomy due to lowering of slough clearance rates. Hence we recommend the need for assessment and treatment pre/post operatively of laryngopharyngeal reflux disease in adult patients undergoing tonsillectomy.&lt;/p&gt;

3095 Non-Celiac Gluten Sensitivity (NCGS) Presenting as Laryngopharyngeal Reflux (LPR)

INTRODUCTION: Laryngopharyngeal reflux (LPR) is defined as retrograde passage of stomach contents through the esophagus into the larynx and pharynx. Celiac adhering disease is known to cause more severe reflux, often refractory to anti-secretory medications like proton pump inhibitors (PPI). In those cases, the patient will frequently experience symptom relief by adherence to a gluten free diet (GFD). However, little is known about non-celiac gluten sensitivity (NCGS), and the only commercially available test, Antigliadin (AGA) IgG, is positive in about 60% of patients. We present a case of LPR refractory to anti-secretory medication, low acid diet, and reflux surgery that resolved rapidly on a gluten free diet after diagnosing NCGS. CASE DESCRIPTION/METHODS: A 59 years old woman with PMH of gastric bypass surgery (roux-en-Y), GERD, hypothyroidism, MDD, and migraine presented with symptoms of hoarseness, mucous throat clearing, cough, sour taste, and nocturnal choking/laryngospasm events. Flexible fiberoptic laryngoscopy supported the diagnosis of LPR with classic findings of laryngeal edema, erythema, and inflammatory mucus. Treatment with omeprazole 40 mg BID, ranitidine 300 mg QHS, and aluminum hydroxide/magnesium carbonate failed to resolve her symptoms. Persistent severe acid reflux and strong symptom correlation were confirmed with dual sensor pH impedance while esophageal manometry confirmed hypotonic lower esophageal sphincter pressure. She underwent paraesophageal hernia repair and Dor fundoplication resulting in temporary resolution of symptoms that returned one month postoperatively. Although she was unaware of any gluten intolerance, she was tested for gluten sensitivity. Tissue Transglutaminase (TTG) IgA/IgG and Deamidated Gliadin Peptide (DGP) IgA/IgG were normal, but AGA IgG was elevated (111), suggestive of NCGS. She was instructed to follow a GFD, and within one week, all reflux symptoms had resolved, along with headaches, joint pain, and “foggy” mind. DISCUSSION: The patient had classic signs and symptoms of LPR, responsive to GFD, after NCGS was determined by elevated AGA IgG. NCGS remains the least understood form of gluten sensitivity, unlike its counterparts celiac disease and wheat allergy. By exploring the potential connections between LPR and gluten sensitivity, it becomes apparent that some of these patients have gluten sensitivity as the root cause of their reflux symptoms and laryngeal inflammation. More research is needed to better understand the influential diagnosis of NCGS.

Synthesis and Characterisation of Novel Temperature and pH Sensitive Physically Cross-Linked Poly (N-vinylcaprolactam-co-itaconic Acid) Hydrogels for Drug Delivery.

Previous studies involving poly N-vinylcaprolactam (PNVCL) and itaconic acid (IA) have synthesised the hydrogels with the presence of a solvent and a crosslinker, producing chemically crosslinked hydrogel systems. In this study, however, temperature sensitive PNVCL was physically crosslinked with a pH-sensitive comonomer IA through ultraviolet (UV) free-radical polymerization, without the presence of a solvent, to produce hydrogels with dual sensitivity. The attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy indicated successful polymerisation of the hydrogels. The temperature and pH sensitivity of the hydrogels was investigated. The lower critical solution temperature (LCST) of the gels was determined using the UV spectrometry and it was found that the incorporation of IA decreased the LCST. Rheology was conducted to investigate the mechanical and viscoelastic properties of the hydrogels, with results indicating IA that enhances the mechanical properties of the gels. Swelling studies were carried out at ~20 °C and 37 °C in different buffer solutions simulating the gastrointestinal tract (pH 2.2 and pH 6.8). In acidic conditions, the gels showed gradual increase in swelling while remaining structurally intact. While in basic conditions, the gels had a burst in swelling and began to gradually degrade after 30 min. Results were similar for drug release studies. Acetaminophen was incorporated into the hydrogels. Drug dissolution studies were carried out at 37 °C in pH 2.2 and pH 6.8. It was found that <20% of acetaminophen was released from the gels in pH 2.2, whereas the maximum drug released at pH 6.8 was 74%. Cytotoxicity studies also demonstrated the hydrogels to be highly biocompatible. These results indicate that physically crosslinked P(NVCL-IA) gels possess dual pH and temperature sensitive properties, which may be beneficial for biomedical applications such as drug delivery.

Prevalence of laryngopharyngeal reflux in adult population using 24 hours ambulatory dual probe pH monitoring

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Laryngopharyngeal reflux disease is an under diagnosed condition due to unavailability of the diagnostic tool that is dual probe pH monitoring and is on the rise in adult population according to El Serag by 4% every year since 1976.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Adult patients coming to the outpatient department between April 2017 to April 2018 were evaluated using reflux symptom index score (RSI). Score greater than 13 were suggestive of laryngopharyngeal reflux and patients underwent 24 hours ambulatory dual probe pH monitoring. 7 or more reflux events in study period were diagnostic of laryngopharygeal reflux. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 3000 adult patients were screened for RSI and 1756 (58.3%) had scored greater than 13. Among these patients 893 patients had 7 or more reflux events in pH monitoring. We found a prevalence of 29.76% in our study population.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Prevalence laryngopharyngeal reflux disease needs to assess periodically at regular intervals to create more awareness of the disease and patient education thus preventing from causing chronic illnesses.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma.

Shedding of membrane-bound cell surface proteins, where the extracellular domain is released and found in the circulation is a common phenomenon. A prominent example is CEACAM5 (CEA, CD66e), where the shed domain plays a pivotal role in tumor progression and metastasis. For treatment of solid tumors, the presence of the tumor-specific antigen in the plasma can be problematic since tumor-specific antibodies might be intercepted by the soluble antigen before invading their desired tumor target area. To overcome this problem, we developed a generic procedure to generate bispecific antibodies, where one arm binds the antigen in a pH-dependent manner thereby enhancing antigen clearance upon endosomal uptake, while the other arm is able to target tumor cells pH-independently. This was achieved by incorporating pH-sensitive binding modalities in the common light chain IGKV3-15*01 of a CEACAM5 binding heavy chain only antibody. Screening of a histidine-doped light chain library using yeast surface display enabled the isolation of pH-dependent binders. When such a light chain was utilized as a common light chain in a bispecific antibody format, only the respective heavy/light chain combination, identified during selections, displayed pH-responsive binding. In addition, we found that the altered common light chain does not negatively impact the affinity of other heavy chain only binders toward their respective antigen. Our strategy may open new avenues for the generation of bispecifics, where one arm efficiently removes a shed antigen from the circulation while the other arm targets a tumor marker in a pH-independent manner.

Application of single and dual fluorophore-based pH sensors for determination of milk quality and shelf life using a fibre optic spectrophotometer

Milk is a high nutrient value food substance consumed by the entire population in several forms. Spoilage and degradation of milk and its products during transportation, processing and packaging are some of the major losses by dairy industries. The change in milk pH with time is an indicating factor of milk degradation. This research reports a rapid, sensitive and facile fluorescence-based technique to study the time-based milk degradation at room temperature. Fluorescein isothiocyanate (FITC)/ FITC-dextran (FITC-dex) and Tris (2, 2′-bipyridyl) dichloro ruthenium (II) hexahydrate (Ru-bpy) were used to develop solution phase and immobilized phase pH sensors. Immobilized phase sensors constituted of alginate microspheres (5 ± 3 μm) produced using an air driven atomizer. The pH sensor works in a linear range of 3–8 pH units with a quick response time of 30 s. The percentage recovery of the system lay in the range of 89.23%–101.28% for detection of milk pH. Accurate detection was possible during entire shelf life of milk (˜24 h) and Inter-sample and inter-day reproducibility was checked over 10 days duration. The results clearly indicate that both single and dual fluorophore-based assay in solution phase and immobilized phases can predict milk pH with good accuracy.

Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes.

Every year, approximately 1.2 million cases of colorectal carcinoma (CRC) are newly diagnosed worldwide. Although metastases to distant organs are often fatal complications of CRC, little information is known as to how such metastatic lesions are formed. To reveal the genetic profiles for CRC metastasis, we conducted whole‐exome RNA sequencing on CRC tumors with liver metastasis (LM) (group A, n = 12) and clinical stage‐matched larger tumors without LM (group B, n = 16). While the somatic mutation profiles were similar among the primary tumors and LM lesions in group A and the tumors in group B, the A‐to‐C nucleotide change in the context of “AAG” was only enriched in the LM regions in group A, suggesting the presence of a DNA damage process specific to metastasis. Genes already known to be associated with CRC were mutated in all groups at a similar frequency, but we detected somatic nonsynonymous mutations in a total of 707 genes in the LM regions, but not in the tumors without LM. Signaling pathways linked to such “LM‐associated” genes were overrepresented for extracellular matrix‐receptor interaction or focal adhesion. Further, fusions of the ADAP1 (ArfGAP with dual PH domain 1) were newly identified in our cohort (3 out of 28 patients), which activated ARF6, an ADAP1‐substrate. Infrequently, mutated genes may play an important role in metastasis formation of CRC. Additionally, recurrent ADAP1 fusion genes were unexpectedly discovered. As these fusions activate small GTPase, further experiments are warranted to examine their contribution to CRC carcinogenesis.

Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs

In this study, chitosan oligosaccharide (COS)-vanillin imine (COS-Vani Imine)-based dual pH responsive nano-micelles (DPRNs) were synthesized. The resultant DPRNs were used for encapsulating genistein and its ultimate release upon pH change. The overall concept of DPRNs for the targeted delivery of hydrophobic anticancer drugs was successfully demonstrated. The DPRNs were spherical in shape, nanoscale in dimension (71.2–163.4 nm), with dual pH response. The encapsulation/loading of genistein into DPRNs was achieved and the resultant genistein-loaded DPRNs were stable under the physiological pH (˜7.4); under the cancer cell extracellular pH (˜6.8), the amino groups in COS is protonated, thus becoming positively charged, facilitating their adsorption onto negatively charged cancer cells. Under the cancer cell intracellular pH (˜5.0), the genistein-loaded DPRNs were destroyed as a result of the cleavage of pH sensitive benzoic imine, thereby releasing the loaded genistein.

PH/UV Responsive Polymeric Micelles Based on Coumarin to Tune Emulsification/Solidification Performance

AbstractA kind of pH/UV sensitive terpolymer was prepared based on 2‐(dimethylamino) ethyl methacrylate, hydroxyethyl methacrylate, and 7‐(2‐(4‐vinylbenzyloxyl)‐ethoxy)‐4‐methyl‐coumarin. To well trace the self‐assembly process and reversible photo‐cross/de‐cross‐linking, the pH‐ and light‐responsive behaviors at various conditions were investigated by dynamic light scattering and UV‐Vis spectroscopic analysis, respectively. Besides, dual pH‐ and light‐responsive coumarin‐containing polymeric micelles could be used to manipulate the emulsion phases and trigger the solidification of emulsions, which was a big breakthrough in the development of particulate emulsifiers. The emulsifying performance could be predicted by the form of aqueous micellar solutions with a certain pH value before oil‐water homogenization. Different to the effect of pH value lonely, the conversion from emulsification into solidification could be achieved with the synergetic effect of pH value and UV irradiation. This work might cast new insights on tuning emulsification/solidification performance just by adjusting pH value and UV irradiation time without the need for additives.

Fractal evolution of dual pH- and temperature-responsive P(NIPAM-co-AA)@BMMs with bimodal mesoporous silica core and coated-copolymer shell during drug delivery procedure via SAXS characterization

The dual (pH- and temperature-) responsive core-shell structured mesoporous nanomaterial P@BMMs were prepared using bimodal mesoporous silica as a core and poly(N-isopropylacrylamide-co-acrylic acid) P(NIPAM-co-AA) copolymer as a shell. Ibuprofen (IBU) was used as a model drug, and the effects of copolymer-coated shell thickness on drug loading and controlled release behavior were investigated by means of N2 sorption isotherms, dynamic light scattering measurements, X-ray diffraction patterns, Fourier transform infrared spectra, scanning electron and transmission electron microscopy, thermogravimetric profiles, and elemental analysis techniques. Particularly, their fractal evolutions in the drug delivery durations were explored via small angle X-ray scattering methods, demonstrating that the resultant P@BMMs before IBU-loading and after releasing possess the typical fractal features with spherical morphology. Meanwhile, the estimation for shell thickness of P@BMMs coating in different time intervals indicated that the drug-loaded capacity was improved with the increasing shell thickness, but drug-released rate varies, strongly depending on both shell thickness and release conditions. The drug delivery mechanism was preliminarily explored, following the Korsmeyer-Peppas model. Finally, cytotoxicity in cell and pharmacokinetic of released-IBU from hybrid nanocomposite in mice via intravenously injection were preliminarily explored.