Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn® H40 core, poly(l-lactide) (PLA) inner-shell, and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction. The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), gel permeation chromatography (GPC), differential scanning calorimeter (DSC), and thermal gravimetric analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm. Interestingly, these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT), most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these reductive unimolecular micelles. In vitro release studies revealed that under the reduction-stimulus, the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells. Methyl tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX. All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.     

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by 1H molecular diffusion NMR and 19F spin diffusion NMR

R(f)-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol-gel two-phase coexistence and low surface erosion. In this study, (1)H molecular diffusion nuclear magnetic resonance (NMR) and (19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R(f)-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of (19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R(f) core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R(f) group and the PEG chain) than that of FU while the opposite is true in the PEG-water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R(f) core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications.     

Model of drug-loaded fluorocarbon-based micelles studied by electron-spin induced (19)f relaxation NMR and molecular dynamics simulation

Rf-IPDU-PEGs belong to a class of fluoroalkyl-ended poly(ethylene glycol) polymers (Rf-PEGs), where the IPDU (isophorone diurethane) functions as a linker to connect each end of the PEG chain to a fluoroalkyl group. The Rf-IPDU-PEGs form hydrogels in water with favorable sol-gel coexistence properties. Thus, they are promising for use as drug delivery agents. In this study, we introduce an electron-spin induced 19F relaxation NMR technique to probe the location and drug-loading capacity for an electron-spin labeled hydrophobic drug, CT (chlorambucil-tempol adduct), enclosed in the Rf-IPDU-PEG micelle. With the assistance of molecular dynamics simulations, a clear idea regarding the structures of the Rf-IPDU-PEG micelle and its CT-loaded micelle was revealed. The significance of this research lies in the finding that the hydrophobic drug molecules were loaded within the intermediate IPDU shells of the Rf-IPDU-PEG micelles. The molecular structures of IPDU and that of CT are favorably comparable. Consequently, it appears that this study opens a window to modify the linker between the Rf group and the PEG chain for achieving customized structure-based drug-loading capabilities for these hydrogels, while the advantage of the strong affinity among the Rf groups to hold individual micelles together and to interconnect the micellar network is still retained in hopes of maintaining the sol-gel coexistence of the Rf-PEGs.     

Comparison of drug delivery properties of PEG-<Emphasis Type="Italic">b</Emphasis>-pdhpc micelles with different compositions

An anti-tumor drug doxorubicin was encapsulated in micelles of poly（ethylene glycol）-b-poly（2,2-dihydroxyl-methyl propylene carbonate）（PEG-b-PDHPC） diblock copolymers.The morphology of both blank micelles and drug loaded micelles was characterized by TEM.The in vitro drug release profiles of micelles were investigated.The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts.The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitro anti-tumor efficacies.The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs.The drug release rate of PEG₄₅-b-PDHPC₃₄ micelles was faster than that of mPEG₁₁₄-b-PDHPC₂₆,micelles.Both of the two block copolymers were non-toxic.The confocal laser scanning microscopy and flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells.The PEG₄₅-b-PDHPC₃₄ micelles exhibited higher anti-tumor activity comparing to mPEG₁₁₄-b-PDHPC₂₆ micelles.     

RAFT synthesis of thioether-based,AB diblock copolymer nanocarriers for reactive oxygen species–triggered release

A well-defined AB diblock copolymer of 2-vinyl-4,4-dimethylazlactone (VDA) and N,N-dimethylacrylamide (DMA) was generated by reversible addition-fragmentation chain transfer (RAFT) radical polymerization. The VDA-DMA diblock copolymer was reacted with 2-(methylthio)ethylamine (MTEA) and 3-(methylthio)propylamine (MTPA) to yield two novel thioether functional diblock copolymers whose structure was confirmed using ¹H NMR and FTIR spectroscopy. Both diblock copolymers formed micelles (20–30 nm) in aqueous media as confirmed by dynamic light scattering (DLS) and transmission electron microscopy. The self-assembled micelles were loaded with Nile Red, a model hydrophobic drug to study their ROS-triggered release mechanism. On addition of hydrogen peroxide (H₂O₂), the most common ROS species, the hydrophobic thioether core of these micelles oxidized, and both diblock copolymers became more hydrophilic. This triggered their disassembly and subsequent cargo release as characterized by UV–visible spectroscopy. The Nile Red loaded micelles demonstrated similar in-vitro ROS-mediated release when exposed to endogenous oxidants in a model inflammation environment simulated by the presence of activated macrophages. The responsive nanomaterials developed in this article have promising potential as drug carriers in applications where ROS-triggered delivery of cargo is required such as in inflammatory conditions.     

Dual crosslinked pH‐ and temperature‐sensitive hydrogel beads for intestine‐targeted controlled release

Novel drug‐loaded hydrogel beads for intestine‐targeted controlled release were developed by using pH‐ and temperature‐sensitive carboxymethyl chitosan‐graft‐poly(N,N‐diethylacrylamide) (CMCTS‐g‐PDEA) hydrogel as carriers and vitamin B₂ (VB₂) as a model drug. The hydrogel beads were prepared based on Ca²⁺ ionic crosslinking in acidic solution and formed dual crosslinked network structure. The structure of hydrogel and morphology of drug‐loaded beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The study about swelling characteristics of hydrogel beads indicated that the beads had obvious pH‐ and temperature‐sensitivity. In vitro release studies of drug‐loaded beads were carried out in pH 1.2 HCl buffer solution and pH 7.4 phosphate buffer solution at 37°C, respectively. The results indicated that the dual crosslinked method could effectively control the drug release rate under gastrointestinal tract (GIT) conditions, which was superior to traditional single crosslinked beads. In addition, the effects of grafting percentage, pH value, and temperature on the release behavior of the VB₂ were investigated. The drug release mechanism of CMCTS‐g‐PDEA drug‐loaded beads was analyzed by Peppa's potential equation. According to this study, the dual crosslinked hydrogel beads based on CMCTS‐g‐PDEA could serve as suitable candidate for drug site‐specific carrier in intestine. Copyright © 2009 John Wiley & Sons, Ltd.     

In situ fabrication of paclitaxel‐loaded core‐crosslinked micelles via thiol‐ene “click” chemistry for reduction‐responsive drug release

In this study, a facile method to fabricate reduction‐responsive core‐crosslinked micelles via in situ thiol‐ene “click” reaction was reported. A series of biodegradable poly(ether‐ester)s with multiple pendent mercapto groups were first synthesized by melt polycondensation of diol poly(ethylene glycol), 1,4‐butanediol, and mercaptosuccinic acid using scandium trifluoromethanesulfonate [Sc(OTf)₃] as the catalyst. Then paclitaxel (PTX)‐loaded core‐crosslinked (CCL) micelles were successfully prepared by in situ crosslinking hydrophobic polyester blocks in aqueous media via thiol‐ene “click” chemistry using 2,2′‐dithiodiethanol diacrylate as the crosslinker. These PTX‐loaded CCL micelles with disulfide bonds exhibited reduction‐responsive behaviors in the presence of dithiothreitol (DTT). The drug release profile of the PTX‐loaded CCL micelles revealed that only a small amount of loaded PTX was released slowly in phosphate buffer solution (PBS) without DTT, while quick release was observed in the presence of 10.0 mM DTT. Cell count kit (CCK‐8) assays revealed that the reduction‐sensitive PTX‐loaded CCL micelles showed high antitumor activity toward HeLa cells, which was significantly higher than that of reduction‐insensitive counterparts and free PTX. This kind of biodegradable and biocompatible CCL micelles could serve as a bioreducible nanocarrier for the controlled antitumor drug release. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 99–107     

Fabrication of biofunctional complex micelles with tunable structure for application in controlled drug release

In acidic solution, complex micelles were formed by diblock copolymers of poly (ethylene glycol)-b-poly (ε-caprolactone) (PEG-b-PCL) and folate-poly (2-(dimethylamino) ethyl methylacrylate)-b-poly (ε-caprolactone) (Fol-PDMAEMA-b-PCL) with a PCL core, a mixed PEG/Fol-PDMAEMA shell. The surface charge of the complex micelles was positive at acidic surroundings for the protonated PDMAEMA. With increasing pH value to 7.4 (above pK _a of PDMAEMA), these micelles could convert into a core-shell-corona (CSC) structure composing a hydrophobic PCL core, a collapsed PDMAEMA shell, and a soluble PEG corona. Compared to core-shell micelles formed by PEG-b-PCL, micelles with CSC structure can prolong degradation by enzyme. Doxorubicin was physically loaded into the PCL core. The drug release rate was pH-dependent. At pH 5.5, complex micelles with core-shell structure showed faster drug release rate, while at pH 7.4, complex micelles gained CSC structure which control the drug release at a lower rate. The multifunctional complex micelles were prepared for enhanced tumor therapy.     

Development of Antibacterial,Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R² = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.     

Investigation of a novel thermogelling hydrogel for a versatility of drugs delivery

The P(CL-PDO)-PEG-(P(CL-PDO)(PECP) copolymer hydrogel is an attractive thermogelling material for practical applications due to the fast dissolution of the copolymer in water and good stability of the resultant sol solution that is beneficial for guest matter mixing. In this paper, the degradation properties and drug release behavior of the hydrogel loaded with various types of drugs were evaluated. The integrity of the PECP hydrogel could preserve for 2?weeks and became viscous liquid after degradation time of 21?weeks. With the degradation time, both the molecular weight and weight loss of the hydrogel decreased gradually. NMR analysis of the degraded products indicated that the chain breaking of the copolymer mainly occurred within the sequence structures of PDO-PDO or PDO-PCL, implying the acceleration effect of PDO unit to the degradation of hydrogel. Three distinct types of drugs including small molecular hydrophobic, small molecular hydrophilic and hydrophilic macromolecular drugs were loaded into the PECP hydrogel to evaluate their release profiles. The result showed that the releasing periods for macromolecular protein or hydrophobic drug were extended to more than one month. Since these two types of drugs are loaded within different regions of the hydrogel due to their different hydrophobic/hydrophilic nature, the PECP hydrogel is expected to develop injectable system loaded with a versatility of drugs or guest matter for synergetic effect.     

In vitro drug release from silicone rubber–polyacrylamide composite

Composite materials containing drugs were prepared from silicone rubber and hydrogel. Cross linked polyacrylamide (PAAm) hydrogel particles were incorporated into a silicone rubber to enhance the hydrophilicity and drug release capacity of silicone rubber as a matrix. Progesterone and Thymol Blue were used as a hydrophobic and hydrophilic drug model, respectively. Different amounts of polyacrylamide (PAAm) were mixed with the drugs and uncured silicone rubber at room temperature. The composite matrices were formed using a compression molding press and cured by thermal and γ-irradiation curing methods. In vitro drug release behavior of composites and their physical and mechanical properties were investigated. The results indicated that the hydrophilic character of silicone rubber was more pronounced with increasing the amount of PAAm. Also, a significant effect on the drug release profiles was observed. The γ-irradiation curing method improved mechanical properties of composites and affected the drug release profiles. It was found that the amounts of released progesterone from γ-irradiated samples increased in comparison with the thermally cross linked composite since released Thymol Blue was reduced.     

Self‐Assembly Drug Delivery System Based on Programmable Dendritic Peptide Applied in Multidrug Resistance Tumor Therapy

In recent decades, diverse drug delivery systems (DDS) constructed by self‐assembly of dendritic peptides have shown advantages and improvable potential for cancer treatment. Here, an arginine‐enriched dendritic amphiphilic chimeric peptide CRRK(RRCG(Fmoc))₂ containing multiple thiol groups is programmed to form drug‐loaded nano‐micelles by self‐assembly. With a rational design, the branched hydrophobic groups (Fmoc) of the peptides provide a strong hydrophobic force to prevent the drug from premature release, and the reduction‐sensitive disulfide linkages formed between contiguous peptides can control drug release under reducing stimulation. As expected, specific to multidrug resistance (MDR) tumor cells, the arginine‐enriched peptide/drug (PD) nano‐micelles show accurate nuclear localization ability to prevent the drug being pumped by P‐glycoprotein (P‐gp) in vitro, as well as exhibiting satisfactory efficacy for MDR tumor treatment in vivo. This design successfully realizes stimuli‐responsive drug release aimed at MDR tumor cells via an ingenious sequence arrangement.     

Visible‐Light‐Triggered Drug Release from TiO2 Nanotube Arrays: A Controllable Antibacterial Platform

In this work, we use a double‐layered stack of TiO₂ nanotubes (TiNTs) to construct a visible‐light‐triggered drug delivery system. The key for visible light drug release is a hydrophobic cap on the nanotubes containing Au nanoparticles (AuNPs). The AuNPs allow for a photocatalytic scission of the hydrophobic chain under visible light. To demonstrate this principle, we loaded ampicillin (AMP) into the lower part of the TiO₂ nanotube stack, triggered visible‐light‐induced release, and carried out antibacterial studies. The release from the platform becomes most controllable if the drug is silane‐grafted in the hydrophilic bottom layer for drug storage. Thus, visible light photocatalysis can also determine the release kinetics of the active drug from the nanotube wall.     

Fluoroalkenyl, fluoroalkynyl and fluoroalkyl phosphines

A review of the methods available for the preparation of monodentate P(III) compounds containing fluoroalkenyl, fluoroalkynyl and fluoroalkyl groups is given. The synthesis, properties and coordination chemistry of some fluoroalkenyl- and fluoroalkynyl-containing phosphines derived from HFC-134a (CF₃CH₂F) and HFC-245fa (CF₃CH₂CH₂F) is summarised. The development of the reaction between trimethylsilyl-containing phosphines and R_fI which provides a general method by which bulky fluoroalkyl groups, such as i-C₃F₇, t-C₄F₉, c-C₆F₁₁, can be readily introduced into phosphorus(III) centres is reported. Together these methods provide a way of generating P(III) systems of the type R_3−nP(R_f)_n capable of possessing a wide range of steric and electronic properties.     

Stabilization and activation of Pluronic micelles for tumor-targeted drug delivery

In order to be used as drug carriers, Pluronic micelles require stabilization to prevent degradation caused by significant dilution accompanying IV injection. This article studies three routes of Pluronic micelle stabilization. The first route was direct radical crosslinking of micelles cores which resulted in micelle stabilization. However, this compromised the drug loading capacity of Pluronic micelles. In the second route, a small concentration of vegetable oil was introduced into diluted Pluronic solutions. This decreased micelle degradation upon dilution while not compromising the drug loading capacity of oil-stabilized micelles. The third route was a novel technique based on polymerization of the temperature-responsive LCST hydrogel in the core of Pluronic micelles. The hydrogel phase was in a swollen state at room temperature, which provided a high drug loading capacity of the system. The hydrogel collapsed at physiological temperatures which locked the core of micelles thus preventing them from fast degradation upon dilution. This new drug delivery system was called Plurogel®. Phase transitions in Plurogel® caused by variations in temperature or concentration were studied by the EPR. The effect of Pluronic concentration in the incubation medium on the intracellular uptake of two anti-cancer drugs was studied. At low Pluronic concentrations, when the drugs were located in the hydrophilic environment, drug uptake was increased, presumably due to the effect of a polymeric surfactant on the permeability of cell membranes. In contrast, when the drugs were encapsulated in the hydrophobic cores of Pluronic micelles, drug uptake by the cells was substantially decreased. This may be advantageous in the prevention of undesired drug interactions with normal cells. Ultrasonication enhanced intracellular drug uptake from dense Pluronic micelles. These findings permitted the formulation of a new concept of a localized drug delivery.     

Physicochemical Nature of Perfluoroalkyl Compounds Induced by Fluorine

Perfluoroalkyl (R_f) compounds have unique characters represented by a significantly high hydrophobic property, which often makes us consider that R_f groups should be interacted with each other via the ‘hydrophobic interaction’ as found for a normal hydrocarbon. Due to a similar intuitive and simplistic speculation, the R_f‐specific material properties have long been enveloped in darkness for comprehensive understanding, which should lucidly be discussed within a framework of physical chemistry. Here, we show studies on the stratified dipole arrays (SDA) theory, which readily explains the R_f‐specific material characters in a comprehensive manner based on only a few fundamental physical parameters of fluorine. The SDA theory encompasses some conventional theories that account for only a part of material properties. In addition, we show that the concept of vibrational spectroscopy of R_f compounds should also be revised, since the mass of fluorine is larger than that of carbon, which is opposite to the hydrocarbon case. In this manner, chemistry of R_f compounds needs another fully revised concept, which cannot be replaced by an extended concept of normal hydrocarbon compounds.     

Synthesis and supramolecular self‐assembly of thermosensitive amphiphilic star copolymers based on a hyperbranched polyether core

A novel amphiphilic thermosensitive star copolymer with a hydrophobic hyperbranched poly (3‐ethyl‐3‐(hydroxymethyl)oxetane) (HBPO) core and many hydrophilic poly(2‐(dimethylamino) ethyl methacrylate) (PDMAEMA) arms was synthesized and used as the precursor for the aqueous solution self‐assembly. All the copolymers directly aggregated into core–shell unimolecular micelles (around 10 nm) and size‐controllable large multimolecular micelles (around 100 nm) in water at room temperature, according to pyrene probe fluorescence spectrometry and ¹H NMR, TEM, and DLS measurements. The star copolymers also underwent sharp, thermosensitive phase transitions at a lower critical solution temperature (LCST), which were proved to be originated from the secondary aggregation of the large micelles driven by increasing hydrophobic interaction due to the dehydration of PDMAEMA shells on heating. A quantitative variable temperature NMR analysis method was designed by using potassium hydrogen phthalate as an external standard and displayed great potential to evaluate the LCST transition at the molecular level. The drug loading and temperature‐dependent release properties of HBPO‐star‐PDMAEMA micelles were also investigated by using indomethacin as a model drug. The indomethacin‐loaded micelles displayed a rapid drug release at a temperature around LCST. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 668–681, 2008     

Preparation and characteristics of linoleic acid-grafted chitosan oligosaccharide micelles as a carrier for doxorubicin

The linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) (CSO-LA) was synthesized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and the effects of molecular weight of CSO and the charged amount of LA on the physicochemical properties of CSO-LA were investigated, such as CMC, graft ratio, size, zeta potential. The results showed that these chitosan derivatives were able to self-assemble and form spherical shape polymeric micelles with the size range of 150.7–213.9 nm and the zeta potential range of 57.9–79.9 mV, depending on molecular weight of CSO and the charged amount of LA. Using doxorubicin (DOX) as a model drug, the DOX-loaded CSO-LA micelles were prepared by dialysis method. The drug encapsulation efficiencies (EE) of DOX-loaded CSO-LA micelles were as high as about 75%. The sizes of DOX-loaded CSO-LA micelles with 20% charged DOX (relating the mass of CSO-LA) were near 200 nm, and the drug loading (DL) capacity could reach up to 15%. The in vitro release studies indicated that the drug release from the DOX-loaded CSO-LA micelles was reduced with increasing the graft ratio of CSO-LA, due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic segments of CSO-LA. Moreover, the drug release rate from CSO-LA micelles was faster with the drug loading. These data suggested the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties.     

Chemical synthesis of MnFe2O4/chitosan nanocomposites for controlled release of ofloxacin drug

In this study, we synthesized ofloxacin‐loaded MnFe₂O₄ nanoparticles (NPs) surface modified with chitosan (CS‐MnFe₂O₄) for prolonged antibiotic release in a controlled manner. It was found that the synthesized CS‐MnFe₂O₄ was spherical in shape with an average size of 30–50 nm, low aggregation, and good magnetic responsibility. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 86% of drug load and can release ofloxacin over a sustained period of 3 days. The release kinetics study reveals that the drug follows zero order kinetics and the mechanism of drug release is diffusion‐controlled type. These results indicated that CS‐MnFe₂O₄ NPs with pH‐sensitive properties can be used as candidates for intestinal targeted drug delivery through oral administration by avoiding the drug release in the highly acidic gastric fluid region of the stomach.     

Rhodium-catalyzed α-fluoroalkylation reaction of ketones using silyl enol ethers

The treatment of silyl enol ethers with fluoroalkyl halides (R_f-X) in the presence of RhCl(PPh₃)₃ gave α-fluoroalkylated ketones. It seems that a rhodium complex derived from the silyl enol ether and RhCl(PPh₃)₃ played an important role for the oxidative addition of fluoroalkyl halides and the reductive elimination of the product.