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Background:: pH sensitive dendrimers attached to nanocarriers, as one of the drug release systems, have become quite popular due to their ease of manufacture in experimental conditions and the ability to generate fast drug release in the targeted area. This kind of fast release behavior cannot be represented properly in most of the existing kinetic mathematical models. Besides, these models have either no pH dependence or pH dependence added separately. Therefore, they remained one dimensional. Objective:: The aim of this study was to establish the proper analytic equation to describe the fast release of drugs from pH sensitive nanocarrier systems. Then, to combine it with the pH dependent equation for establishing a two-dimensional model for whole system. Methods:: We used four common kinetic models for the comparison and we fitted them to the release data. As a result, only Higuchi and Korsmeyer-Peppas models show acceptable suitable results. None of these models have pH dependence. To get a better description for pH triggered fast release, we observed the behavior of the slope angle of the release curve. Then we proposed a new analytic equation by using relation between the slope angle and time. Result:: By adding a pH dependent equation, we assumed the drug release is “on” or “off” above/below specific pH value and we modified a step function to get a desired behavior. Conclusion:: Our new analytic model shows good fitting, not only one-dimensional time dependent release, but also two-dimensional pH dependent release, that provides a useful analytic model to represent release profiles of pH sensitive fast drug release systems.

The aim of present study was to prepared ocular in-situ gel to increase the residence time of drug in cornea for improvement of ocular bioavailability of drug. In situ gel of Loteprednol etabonate was prepared by using carobopol 940 and different grades of HPMC in different ratios by pH triggered method. The prepared in situ gels were evaluated for pH, drug content, viscosity, gelling time, gelling strength spreadability and sterility testing. In vitro drug release study was carried by using diffusion cell with dialysis membrane. The drug content and pH of the formulation were found to be satisfactory. The gelling strength was found to be in the range of 34 seconds to 91 seconds. The viscosity and spredability of the formulations were found to be satisfactory. Formulation F5 containing 0.3 % carobopol 940 and 0.6 % HPMC K4M showed highest drug release of 80.30 %. The developed formulations showed sustained release of drug up to 8 hrs. From in-vitro drug release studies, it could be concluded that the developed in-situ gelling systems were thus a better alternative to conventional eye drops.

Polymer nanoparticles (NPs) have attracted significant interest in the past years for drug delivery and triggered release. However, it remains a significant challenge to produce polymer NPs with controlled properties and tunable drug loading. Traditional nanoprecipitation often leads to low drug loading. This study reports the development of a new microfluidic nanoprecipitation approach for making polymer NPs with tunable drug loading up to 50%. The synthesized curcumin-loaded shellac NPs remain very stable for the period of our experiments (10 days) under acidic conditions (pH 4.5), but release the payload at neutral pH in a sustained manner. This work provides a new strategy for making drug-loaded polymer NPs with tunable drug loading and triggered release.

The most advantageous and attractive property of photoacoustic imaging is its capability to visualize and differentiate multiple species according to their unique absorbance profiles simultaneously in a single mixture. We here report the pH-sensitive near-infrared (NIR) croconaine (Croc) dyes-loaded copolymeric PEG-PLGA nanoparticles (NPs) for

Herein we report L-cysteine (Cys)-mediated copper nanoclusters (CuNCs) with assembly-to-monodispersion switching by pH-triggered surface modulation. Aggregated red emissive (R)-CuNCs@Cys at pH = 3 turns to monodispersed blue emissive (B)-CuNCs@Cys at pH = 10, due to the change from weak electrostatic interactions to strong Cu–N bonds that play a decisive role.

Developing radical oxygen species (ROS)-generating nanoreactors as new "antibiotics" is a promising strategy for the treatment of multidrug-resistant (MDR) biofilm infections. Herein, we designed and fabricated silver nanoparticle-decorated calcium peroxide (CaO2) nanoreactors (CPA) for combating MDR biofilms. CPA could locally boost ROS production as oxidative stress amplifiers in a pH-triggered and self-catalytic manner in acidic biofilms, where H2O2 was released by the hydrolysis of CaO2 and sequentially catalyzed by Ag NPs in situ to generate O2˙-, thereby efficiently disrupting mature biofilms and killing bacteria.

Integrating silica with organic nanoparticles can generate unique properties. Here pillar[5]arene/silica hybrid vesicles were constructed based on the amphiphilic and rigid properties of pillararenes, as well as the catalytic hydrolysis of tetraethoxysilane. Such vesicles exhibited the high strength of silica and unique molecular recognition of pillararenes, both of which could tune the pH-triggered release behavior. Furthermore, a rhodamine B derivative with hexyl group (RhB-C6) was synthesized, which can form a complex with the pillar[5]arene. Based on the host-guest interaction and high strength of silica, the hybrid vesicles could load more RhB-C6 and the rhodamine B was released more slowly compared with the organic vesicles.

To augment the antitumor efficacy and minimize the significant side effects of chemotherapeutic drugs on health organs, a novel albumin-mimicking nanodrug, which is based on zwitterionic poly(glutamatyl lysine-co-cysteine) peptides scaffold, is developed to enhance pH-triggered tumor targeting via prolonging circulation time and accelerating cellular internalization. Results showed that the internalization of the nanodrug by MCF-7 cells is much faster than that by Doxil and even comparable to that by free doxorubicin (Dox) at tumor microenvironmental pH 6.7, whereas the internalization of the nanodrug is only 27.4 ± 7.6% of the Doxil by RAW-264.7 cells. Moreover, the significantly prolonged circulation time of the "stealthy" nanodrug was also comparable to that of the long circulating Doxil. As a result, the accumulation of the nanodrug in the tumor is much higher than that in the liver and kidney before the circulation half-life, which is significantly different from most other nanodrugs accumulated in the liver and kidney in this time scale. The tumor inhibition rate of the nanodrug was much higher than that of Doxil (93.2 ± 3.0% vs 54.2 ± 6.5%) after 18 day treatment, while the average bodyweight of the mice treated by the nanodrug was 26.9 ± 6.7% higher than that by Doxil. This indicated that the synergetic effect of long circulation time and fast cellular internalization of the nanodrug can significantly augment tumor targeting. This method might rejuvenate the traditional chemotherapeutic treatment.

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

Objectives: The objective of present study was to formulate and optimize ophthalmic pH triggered in situ gelling system of tobramycin in order to enhance residence time and provide prolonged drug release. Methods: Two factor three level full factorial design was applied to study the effect of concentration of carbopol 980 and HPMC K4M on dependent parameters such as viscosity, gel strength and gelling capacity. Overlay plot method was used to optimize the formulation. The optimized formula was evaluated for clarity, pH, viscosity, gel strength, gelling capacity, in vitro drug diffusion, sterility test, ocular irritancy test, Isotonicity test, antimicrobial efficacy and stability studies. Results and Discussion: The results showed that increasing the concentration of carbopol980 and HPMC K4M, there was increased in the gelling capacity, its gelling strength and viscosity. All the formulations had pH around 5. The optimized formulation prolonged the drug release for eight hours which had a composition of 0.48% carbopol980 and 0.52% HPMC K4M. From the kinetic modelling it showed that it followed Higuchi model for drug diffusion. The gel formed in vitro produced sustained drug release up to 8 hr. Results showed no significant change in the results of appearance, pH, viscosity, gelling capacity and drug content when stored at accelerated condition and room temperature for a period of one month. Conclusion: Optimized formulation was sterile, non-irritant, isotonic and stable and also it can be substitute to conventional eye drops formulations of tobramycin which could provide a sustained release for a period of eight hours.

The development of switches responding to specific pH changes was particularly useful in wide application fields. Owing to flexible switches simulated by pH, i-motif DNAs are widely used as a pH sensor. But its character of structure transition strongly dependent on acidic pH severely hampers the application of i-motif DNA in physiological media. Herein, we report the stable i-motif structure formed at a physiological pH triggered by spatial confinement of silica nanochannels. Three classic DNA chains containing 21-mer i-motif domain base-pairs and a single-stranded multiply (T)n spacer, 5'-COOH-(T)n-CCCTAACCCTAACCCTAACCC-3', were employed to evaluate the enhanced stability of i-motif structure. Compared to their free states in a dilute solution, the transition pH of all i-motif DNAs decorated in nanochannels remarkably shifts toward a neutral pH. Moreover, the transition midpoint can be tuned sensitively over the physiologically relevant pH range through slightly varying the length of T base spacer. Density functional theory (DFT) calculations validate that the increased proton density in a nanochannel triggers the formation of an i-motif structure under a neutral pH. Finally, this i-motif DNA based nanochannels electrode was successfully employed to monitor pH in brain microdialysates followed by cerebral ischemia. The present approach is not limited by fundamental investigation for DNA conformation but may extend toward the manipulation of i-motif based structures for artificial molecular machines and signaling systems.

A sandwich structured bifunctional nanocarrier (rGO@msilica) composed of an inner layer of reduced graphene oxide (rGO) and an outer layer of mesoporous silica (msilica) was developed for synergistic chemo-photothermal therapy. The rGO@msilica not only acted as a pH-triggered drug nanocarrier but also worked as a near-infrared (NIR) photothermal agent. The loaded drug, doxorubicin (DOX), in the rGO@msilica nanocarrier was controllably released in the acidic tumor microenvironment. Moreover, the cancer cells were ablated by laser irradiation (808 nm), contributing to the high photothermal conversion efficiency of the rGO core. With this two-in-one system

While emulsion-templated porous polymers (polyHIPEs) with pH-controlled wetting behaviours are advantageous for the removal of oils from oil–water mixtures, they are easily clogged by oils and are not suitable for separating mixtures consisting of a small amount of water and a large amount of oils. Herein, we report the fabrication of amphiphobic polyHIPEs from high internal phase emulsions via simultaneous solution polymerization and interface-induced polymerization. After pH adjustment with an HCl solution, the amphiphobicity of the polyHIPEs was transformed into hydrophilicity–oleophobicity, which enabled water to be selectively absorbed and separated from oil–water mixtures, and the pH-triggered transition achieved the separation in a controlled manner. Moreover, the absorption was realized in a continuous manner under an external pressure provided by a pump. The resulting hydrophilic–oleophobic polyHIPEs also absorbed water from emulsified oil–water mixtures (emulsions). The pH-triggered transition from amphiphobicity to hydrophilicity–oleophobicity and the selective absorption of water from oil–water mixtures in a continuous manner make the polyHIPEs excellent candidates for the controlled removal of water from oil–water mixtures.

A pH-triggered G-triplex (G3) switch is demonstrated to operate in K+ using a planar ligand enabling reversible iminium-alkanolamine conversion as the G3 structuring-destructuring initiator.

In this paper, we developed a novel strategy of preparing doxorubicin (DOX) nanocrystal (NC) exerting spherical particles with a diameter of 102 nm, which experienced following coating of chondroitin sulphate derivative (CSOA) shell via electrostatic and hydrophobic interactions. Such multifunctional outerwear resulted in drug nanocapsules with high drug loading content up to 70% and high colloidal stability under physiological conditions. It exhibited accelerated drug release behaviour when dispersing in hyaluronidase (HAase) containing medium or incubated with cancer cells. CSOA/NCs were effectively taken up by cancer cells via CD44 receptor-mediated endocytosis, but were rarely internalised into normal fibroblasts. With the comparison of typical drug-loaded micelles system (DOX/PEG-PCL), CSOA/NCs showed greater inhibition to cancer cells due to the targeted and sensitive drug delivery.

As a novel type of bio-functional material, DNA hydrogels have attracted more and more attention due to their successful applications in 3D cell culturing and tissue engineering for the designable and programmable responsiveness. Herein, we have developed a pH-triggered DNA hydrogel based on a clamped hybridization chain reaction(C-HCR). In this system, a DNA switch was designed, which can release the initiator strand in a controllable way via the formation of the C-G·C+ triplex under the pH stimuli. While the pre-gelation solution is stable in neutral environment, the C-HCR will trigger the sol-gel transition as the pH decreased to 5.0. This strategy has endowed the DNA hydrogel with good controllability for triggering, which also shows potential in intellectual responsiveness to certain stimuli.

In nanoplatform-based tumor treatment, combining chemotherapy with hyperthermia therapy is an interesting strategy to achieve enhanced therapeutic efficacy with low dose of delivery drugs. Compared to photothermal therapy, magnetic hyperthermia has few restrictions on penetrating tissue by an alternating magnetic field, and thereby could cure various solid tumors, even deep-tissue ones. In this work, we proposed to construct magnetic nanocomposites (Fe3O4@PDA@ZIF-90) by the external growth of metal-organic framework ZIF-90 on polydopamine (PDA)-coated Fe3O4 nanoparticles for synergistic magnetic hyperthermia and chemotherapy. In such multifunctional platform, Fe3O4 nanoparticle was utilized as a magnetic heating seed, PDA layer acted as an inducer for the growth of ZIF-90 shell and porous ZIF-90 shell served as drug nanocarrier to load doxorubicin (DOX). The well-defined Fe3O4@PDA@ZIF-90 core-shell nanoparticles were displayed with an average size of ca. 200 nm and possessed the abilities to load high capacity of DOX as well as trigger drug release in a pH-responsive way. Furthermore, the Fe3O4@PDA@ZIF-90 nanoparticles can raise the local temperature to meet hyperthermia condition under an alternating magnetic field owing to the magnetocaloric effect of Fe3O4 cores. In the in vitro experiments, the Fe3O4@PDA@ZIF-90 nanoparticles showed a negligible cytotoxicity to Hela cells. More significantly, after cellular internalization, the DOX-loaded Fe3O4@PDA@ZIF-90 nanoparticles exhibited distinctively synergistic effect to kill tumor cells with higher efficacy compared to chemotherapy or magnetic hyperthermia alone, presenting a great potential for efficient tumor therapy., GRAPHICAL ABSTRACT

Bottom-up synthetic biology thrives to reconstruct basic cellular processes into a minimalist cellular replica to foster their investigation in greater details with a reduced number of variables. Among these cellular features, the endomembrane system is an important aspect of cells which is at the origin of many of their functions. Still, the reconstruction of these inner compartments within a lipid-based vesicle remains challenging and poorly controlled. Herein, we report the use of pH as external trigger to self-assemble compartmentalized giant unilamellar vesicles (GUVs) by either bulk, or droplet-based microfluidics. By co-encapsulating pH sensitive small unilamellar vesicles (SUVs), negatively charged SUVs and/or proteins, we show that acidification of the droplets efficiently produces GUVs while sequestrating the co-encapsulated material with flexibility and robustness. The method enables the simultaneous reconstruction of more than a single cellular phenotype from the bottom-up, corresponding to an important advancement in the current status quo of bottom-up synthetic biology.

Self-propelled chemical motors have found vast promise for applications from nanomedicine to environmental remediation. However, strategies for controlling their directional motion on demand still represents one of the major challenges for the development of smart motor systems to be realized in real-world applications. Here, we report for the first time the design of a novel submarine-like micromotor that is capable of directional vertical motion on centimeter scale by pH-regulated buoyancy control. With the aid of a pH-responsive, hydrophilic/hydrophobic phase-shifting polymer, gas bubbles produced by the biocatalytic metal–organic framework micromotors can be reversibly retained/expelled from the micromotors, leading to the buoyancy-controlled ascending or descending vertical motion. Importantly, anti-cancer drug-loaded micromotors showed directional cytotoxicity to three-dimensional cell cultures, depending on the pH of the cellular environment. We expect this study will open up new avenues for designing directional propulsion mechanisms for chemical motors, showing potential as autonomous robotics for in vivo delivery in complex biological environments.

Using synthetic molecular evolution, we previously discovered a family of peptides that cause macromolecular poration in synthetic membranes at low peptide concentration in a way that is triggered by acidic pH. To understand the mechanism of action of these "pHD peptides", here we systematically explored structure-function relationships through measurements of the effect of pH and peptide concentration on membrane binding, peptide structure, and the formation of macromolecular-sized pores in membranes. Both AFM and functional assays demonstrate the peptide-induced appearance of large pores in bilayers. Pore formation has a very steep pH dependence and is also dependent on peptide concentration. In vesicles, 50% leakage of 40 kDa dextrans occurs at 1 bound peptide per 1300 lipids or only 75 peptides per vesicle, an observation that holds true across a wide range of acidic pH values. The major role of pH is to regulate the amount of peptide bound per vesicle. The physical chemistry and sequence of the pHD peptides affect their potency and pH dependence; therefore, the sequence-structure-function relationships described here can be used for the future design and optimization of membrane permeabilizing peptides for specific applications.

The narrowly dispersed functional silica/poly(di(metacryloylooxy-1-ethoxy) methane-co-acryl amide) (SiO2/P(DMOEM-co-AAm)) core-shell microspheres were synthesized by distillation precipitation polymerization of DMOEM as a degradable crosslinker and AAm as a functional monomer with the presence of 3-(methacryloxy)propyltrimethoxysilane (MPS) modified silica microspheres as seeds. Indole-3-acetic acid (IAA) can be efficiently loaded into the microspheres with a loading capacity of 37.5% via hydrogen-bonding interaction between the carboxylic acid group of IAA and the amide groups on the surface of SiO2/P(DMOEM-co-AAm). The loaded IAA can be triggered released by pH due to the presence of pH-responsive crosslinker (DMOEM).

Improving the deep-tissue phototherapy (PDT) efficiency in the near-infrared (NIR) region has become one of the major challenges in clinics for cancer treatment., Improving the deep-tissue phototherapy (PDT) efficiency in the near-infrared (NIR) region has become one of the major challenges in clinics for cancer treatment. Developing intelligent photosensitizers (PSs) responding to tumor-specific signals sensitively to minimize side effects is another major challenge for tumor phototherapy. Herein, three phenyl-based boron dipyrromethene (BODIPY) compounds with different numbers of diethylaminophenyl groups introduced onto the BODIPY core have been designed and synthesized by the Knoevenagel condensation reaction. The absorbance of these compounds (BDPmPh, BDPbiPh, and BDPtriPh) can be controlled easily for realizing the tunable penetration depth. Moreover, the diethylamino groups in these designed PSs can serve as proton acceptors triggered by the low pH in lysosomes which can enhance the efficacy of photodynamic and photothermal therapy. The corresponding nanoparticles (NPs) of the compounds are prepared through a nanoprecipitation method and in vitro studies demonstrate that the ultra-low drug dosage of BDPtriPh NPs (half-maximal inhibitory concentration, IC50 = 4.16 μM) is much lower than that of BDPmPh NPs (50.09 μM) and BDPbiPh NPs (22.4 μM). In vivo fluorescence imaging shows that these NPs can be passively targeted to tumors by the enhanced permeability and retention (EPR) effect, and BDPtriPh NPs exhibit the fastest accumulation (about 4 hours). In vivo phototherapy indicates that BDPtriPh NPs with the longest NIR absorbance (813 nm) and highest photothermal conversion efficiency (60.5%) can effectively inhibit tumor growth and reduce side effects to normal tissues. This study provides a strategy to modulate the photoconversion characteristics of PSs for both penetration-depth-tunable and pH-dependent PDT/PTT synergistic cancer therapy in clinics.

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate profiles. The prodrug is completely independent of biotransformations and animal-independent because it becomes an active compound via a pH-triggered intramolecular cyclization-elimination reaction. As a proof-of-concept, the utility of this novel amino AOCOM ether prodrug approach was demonstrated on an antimalarial compound series representing a variety of antimalarial 4(1H)-quinolones, which entered and failed preclinical development over the last decade. With the amino AOCOM ether prodrug moiety, the 3-aryl-4(1H)-quinolone preclinical candidate was shown to provide single-dose cures in a rodent malaria model at an oral dose of 3 mg/kg, without the use of an advanced formulation technique.

A acid-labile core cross-linked micelle system of amphiphilic triblock copolymer of poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene-alt-maleic anhydride)-block-poly(styrene) (POEGMA-b-PSMA-b-PS) was prepared. The POEGMA-b-PSMA-b-PS triblock copolymers were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization. Doxorubincin (DOX) was entrapped into micellar structure with POEGMA block as a shell and PSMA-b-PS block as a core. Then, core cross-linking was carried out by amidation reaction between 2,2-bis(aminoethoxy)propane and maleic anhydride group inner core. DOX loading content and efficiency were calculated to be 18 and 90 (wt. %), respectively. Core cross-linked micelles illustrated good stability under physiological condition but disassociated rapidly under acidic pH. The DOX release experiments indicated a rapid DOX release at pH 5.0 compared to pH 7.4.

An aqueous two-phase system (ATPS) is a water-in-water biphasic system, which is generally formed by two incompatible polymers. Recently, considerable effort has been dedicated to search for new ATPS polymer pairs to further expand ATPS's applications. In this paper, a new ATPS system based on silk fibroin (SF) and alginate is introduced. A phase diagram was established to show the critical concentrations for the formation of an SF/alginate ATPS. The present system is sensitive to pH stimulus and transformed from an ATPS into a single-phasic system as pH increases above ∼9.5. Circular dichroism, fluorescence emission spectra, hydrodynamic diameter, and ζ-potential data together indicate that the SF chains undergo a dramatic extension as pH is increased, which is the reason underlying the pH-triggered phase transition. As feasible applications of this biphasic system, compartmentalized multiplex immunoassay, controlled encapsulation and release, and hierarchical fiber fabrication were demonstrated using the SF/alginate ATPS.

Layered double hydroxide (LDH) nanoparticles are extensively explored as multifunctional nanocarriers due to their versatility in both the host layer and the interlayer anion. In this study, we report modification of positively charged Cu-containing LDH nanoparticles with a pH-responsive charge-changeable polymer to improve the particle colloidal stability in blood circulation, reduce the nonspecific uptake by normal cells in organs, and subsequently facilitate tumor accumulation and uptake by tumor cells in the acidic tumor microenvironment. In vitro experimental results demonstrate that this promising charge-convertible polymer–LDH nanocarrier well reduces the capture by macrophages in the physiologic medium (pH 7.4) but facilitates the uptake by tumor cells due to detaching of the coated polymer layer in the weakly acidic condition (pH 6.8). Cu-containing LDH nanoparticles also show pH-responsive magnetic resonance imaging (MRI) contrast capacity (i.e., r1 relaxivity). In vivo MRI further confirms effective tumor accumulation of the charge-convertible nanohybrids, with ∼4.8% of the injected dose accumulated at 24 h postintravenous injection, proving the potential as a versatile delivery nanocarrier to enhance the antitumor treatment.

Peptides that self-assemble into nanometer-sized pores in lipid bilayers could have utility in a variety of biotechnological and clinical applications if we can understand their physical chemical properties and learn to control their membrane selectivity. To empower such control, we have used synthetic molecular evolution to identify the pH-dependent delivery peptides, a family of peptides that assemble into macromolecule-sized pores in membranes at low peptide concentration but only at pH < ∼6. Further advancements will also require better selectivity for specific membranes. Here, we determine the effect of anionic headgroups and bilayer thickness on the mechanism of action of the pH-dependent delivery peptides by measuring binding, secondary structure, and macromolecular poration. The peptide pHD15 partitions and folds equally well into zwitterionic and anionic membranes but is less potent at pore formation in phosphatidylserine-containing membranes. The peptide also binds and folds similarly in membranes of various thicknesses, but its ability to release macromolecules changes dramatically. It causes potent macromolecular poration in vesicles made from phosphatidylcholine with 14 carbon acyl chains, but macromolecular poration decreases sharply with increasing bilayer thickness and does not occur at any peptide concentration in fluid bilayers made from phosphatidylcholine lipids with 20-carbon acyl chains. The effects of headgroup and bilayer thickness on macromolecular poration cannot be accounted for by the amount of peptide bound but instead reflect an inherent selectivity of the peptide for inserting into the membrane-spanning pore state. Molecular dynamics simulations suggest that the effect of thickness is due to hydrophobic match/mismatch between the membrane-spanning peptide and the bilayer hydrocarbon. This remarkable degree of selectivity based on headgroup and especially bilayer thickness is unusual and suggests ways that pore-forming peptides with exquisite selectivity for specific membranes can be designed or evolved.

Carbon dots (CDs) have attracted intense attention in tumor nanotheranostics recently; however, those nanotheranostics exhibited similar fluorescence in both normal and tumor tissues, limiting their practical application. In the present work, absolutely “off–on” fluorescent CD-based nanotheranostics was designed for tumor intracellular real-time imaging and pH-triggered DOX delivery via both static quenching by the crosslinking of benzaldehyde-containing diblock copolymers and dynamic quenching because of the surrounding conjugated DOX molecules. The proposed PPEGMA42-b-PFPMA122–(CDs)–DOX nanotheranostics did not exhibit fluorescence in a normal physiological medium, while strong fluorescence recovery occurred in the tumor intracellular microenvironment due to pH-triggered disintegration, releasing the CDs and DOX. The pH-triggered DOX release and absolute “off–on” fluorescence make the proposed nanotheranostics promising for tumor-specific pH-triggered DOX delivery and imaging.

We report here the first AFM single capsule mechanical measurements on hydrogen-bonded polymeric multilayer microcapsules made of poly(vinylpyrrolidone)/poly(methacrylic acid) (PVPON/PMAA) and of poly(-vinylpyrrolidone-co-NH-20)/poly(methacrylic acid) (PVPON-co-NH-20/PMAA), as well as of capsules derived from these systems chemical crosslinking. The stiffness of the non-crosslinked hydrogen-bonded capsules was found to be proportional to the square of the wall thickness which is in agreement with previous observations on other multilayer capsules and continuum mechanical theory. The found elastic modulus of 610 MPa for low pH (= 2) is typical for a highly stable, glass-like structure similar to electrostatically bound multilayers. At pH > 6, (PMAA) capsules obtained through chemical crosslinking of hydrogen-bonded (PVPON/PMAA) multilayers, or crosslinked (PVPON-co-NH-20/PMAA) capsules showed a sharp hundreds-fold stiffness decrease to ∼1 mN/m which was orders of magnitude lower than those reported earlier for polymeric multilayer systems. pH-Triggered softening was reversible and highly reproducible. Softening of both (PMAA) and (PVPON-co-NH-20/PMAA) crosslinked capsules resulted from increased PMAA ionization, and additional dissociation of intermolecular hydrogen bonds occurred in the case of (PVPON-co-NH-20/PMAA) crosslinked system.

Efficient approach was established to improve the drug delivery performance of the pH-triggered prodrug nanoparticles by introducing a polycation block as a pH-sensitive gatekeeper. With the help of the poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) block as a pH-sensitive shell gatekeeper, the proposed core-shell-corona PEG43-b-PDPA65-b-PFPMA36-DOX nanoparticles possessed a higher drug release rate in the simulated acidic tumor intracellular micro-environment while a lower premature drug leakage in the simulated weak basic normal physiological medium, compared with the core-shell PEG43-b-PFPMA36-DOX nanoparticles. The proposed strategy is expected to design high-performance drug delivery systems (DDSs) for tumor treatment, with improved anticancer efficacy but minimized toxic side effects.

Herein, we construct a charge - switchable polymer nano micelles poly (2-(hexamethyl eneimino) ethyl methacrylate) - b - poly (ethylene glycol) monomethyl ether methacrylate) - b - poly (diethyl en...

Metal–organic frameworks (MOFs) have spurred tremendous research interest in the fields of nanoscience and nanotechnology. However, exploring their biomedical applications is still a daunting challenge. In this work, we employed an acid-degradable MOF, zeolitic imidazolate framework-8 (ZIF-8), both as a self-sacrificial template to synthesize uniform size/morphology-controllable hollow mesoporous silica materials (HMSNs) and as a mesopore blocker for fabricating a pH-responsive HMSN-based drug delivery system. Starting from the ZIF-8 template, a layer of mesoporous silica is coated on ZIF-8 and subsequently the template was self-degraded under acidic conditions to obtain HMSNs. A series of monodisperse HMSNs ranging from ca. 80 nm to ca. 3000 nm with morphologies that give rare examples of cubic and dodecahedral morphologies has been prepared. It is demonstrated that the as-made HMSNs possess well-defined mesopores, huge cavities and good biocompatibility, which make them favourable for drug delivery. So, ZIF-8 was then grafted onto the HMSN to block the pore orifice for pH-responsive intracellular anticancer drug release. The results indicated that the ZIF-8-coated HMSN with encapsulated doxorubicin hydrochloride (DOX) was an efficient drug delivery vehicle in cancer therapy using pH-responsive release. This strategy sheds new light on the application of MOF materials and provides great potential for biomedical applications.

We report calcium phosphate (CaP) nanocapsule crowned multiwalled carbon nanotubes (CNT–GSH–G4–CaP) as a novel platform for intracellular delivery of an anticancer drug. As a proof-of-concept, CNT–GSH–G4–CaP demonstrates release of anticancer drug doxorubicin hydrochloride (DOX) within intracellular lysosomes from the interior cavity of CNT upon pH triggered CaP dissolution. Importantly, we found that the CNT with a CaP nanolid can efficiently prevent untimely drug release at physiological pH but promotes DOX release at increased acidic milieu as observed in subcellular compartments such as lysosomes (∼5.0). This “zero premature release” characteristic is of clinical significance in delivering cytotoxic drugs, by reducing systemic toxicity and thus beneficial for the effective anticancer treatment. We envision that this pH triggered CaP crowned CNT nanosystem would lead to a new generation of self-regulated platforms for intracellular delivery of a variety of anticancer drugs.

We developed a pH-triggered in situ gel (ISG) for ocular delivery of vinpocetine to achieve systemic absorption and a brain-targeting effect in rats. Carbopol acted as a gelling agent combined with hydroxypropyl methylcellulose (HPMC) as a viscosity-enhancing agent. The concentration of Carbopol (0.2%, w/v) and HPMC (1.5%, w/v) was optimized for the ISG system. The optimized formulation was evaluated for studies on release in vitro, rheology, differential scanning calorimetry, ocular irritation, residence time, and in vivo pharmacokinetics. The vinpocetine ISG stayed longer in rabbit eyes than vinpocetine ointment. In vivo pharmacokinetics showed that compared with vinpocetine ointment, vinpocetine ISG attained a peak plasma concentration and area under the curve that was 1-2 folds greater in rat plasma. The Drug Targeting Index (DTI) was 1.06 and 1.26 for vinpocetine ointment and vinpocetine ISG, respectively, after ocular administration, showing that vinpocetine ISG had better distribution in rat brain. These results revealed that a pH-triggered ISG system via ocular administration could be an alternative approach compared with traditional ophthalmic formulations.

The aim of the present work was to formulation and evaluation of pH Triggered in-situ Ophthalmic Gel of Besifloxacin Hydrochloride to overcome the drawbacks obtained by conventional eye drop. There are two independent variables were used i.e. Carbopol 934 and HPMC K100. Carbopol 934 were used as gelling agent and HPMC K100 were used as bioadhesive polymer. Besifloxacin Hydrochloride shows activity against a wide range of Gram-positive and negative ocular pathogens: examples are Corynebacterium pseudodiphtheriticum, Moraxella lacunata, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Streptococcus salivarius. The in situ gelling system involves sol-to-gel transition in the cul-de-sac upon instillation to avoid pre corneal elimination. The formulations were prepared by 32 factorial design. The prepared formulations were evaluated for clarity, pH, viscosity, Bioadhesive strength of gel, gel strength gel, Drug Content, In-vitro Drug Release Study, Antibacterial Activity, Isotonicity Evaluation, HET-CAM Test and stability studies. The drug content was in the range of 97-99.57 %. Formulation F5 selected as optimized on the basis of evaluation. It shows highest drug release upto 8hrs. It shows good antibiotic activity against Staphylococcus aureus. The optimized formulation was isotonic with blood cells. It passes sterility test. The optimized formulation passes the ocular irritancy test i.e. HET-CAM Test. The formulation kept for the stability study for 3 months. Short term stability study indicates that room temperature 400±20 was appropriate storage condition for formulations. Keywords: pH Triggered, bioadhesive polymer, Carbopol 934, HPMC K100, HET-CAM Test, Antibacterial Activity.

Boric acid crosslinked carboxymethyl cellulose hydrogels were synthesized to develop pH-triggered release formulations (pH-TRFs) of boron and thiamethoxam. The developed hydrogels showed pH sensitive water absorption capacity (16.75 to 110.80 g/g xerogel). Entrapment of thiamethoxam was done through an ex-situ loading technique. The boron and thiamethoxam release was studied in pH buffer solutions (4.0, 7.0 and 9.2). Release kinetics analysis using mathematical models showed fast release in high pH solution as compared to acidic pH. These pH-TRFs may find usefulness in selective release of nutrients and pesticides in plant rhizospheric zone of problem soils viz. acidic soils and alkaline soils.