PEGylated nanodiamond for chemotherapeutic drug delivery

Nanodiamond (ND) has the excellent biocompatibility, similarly to other sp³-carbon based materials, and is a potential drug carrier for cancer therapy. In our work, firstly, to increase the dispersity and stability of ND (size ~ 140 nm) in vitro under the physiological environment or in cell culture medium and be suitable for biomedicine applications, ND was covalently conjugated with biocompatible polymers, such as hydroxy-polyethylene glycol-4000 (PEG-4000). Secondly, doxorubicin hydrochloride (DOX), a chemotherapy drug, was physically adsorbed onto the PEGylated nanodiamond (ND-PEG-OH). These results revealed that ND-PEG-OH nanoparticle associated DOX (ND-PEG-DOX) could efficiently deliver the drug into the human liver cancer cells (HepG2) via a clathrin-dependent endocytosis pathway, and especially enhance the DOX uptake as compared to DOX alone. The uptake half-life of ND-PEG-DOX (t_1/2 = 3.31 h) was approximately two times that of free DOX uptake (t_1/2 = 1.67 h), which was related to the uptake pathway. The results from the confocal fluorescence microscopy study showed that DOX detached from ND-PEG-DOX composites inside the cytoplasm could migrate and enter the nucleolus to inhibit the cellular growth. Thirdly, in vitro dialysis determination and imaging experiments using the confocal fluorescence microscopy indicated that DOX released from ND-PEG-DOX composites had a slow and sustained drug release capability. In summary, our study has shown that ND-PEG-OH nanoparticles can act as effective drug carriers for cancer therapy.     

Fabrication of PLA/PEG/MWCNT electrospun nanofibrous scaffolds for anticancer drug delivery

In the present study, polylactic acid (PLA)/polyethylene glycol (PEG)/multiwalled carbon nanotube (MWCNT) electrospun nanofibrous scaffolds were prepared via electrospinning process and their applications for the anticancer drug delivery system were investigated. A response surface methodology based on Box–Behnken design (BBD) was used to evaluate the effect of key parameters of electrospinning process including solution concentration, feeding rate, tip–collector distance (TCD) and applied voltage on the morphology of PLA/PEG/MWCNT nanofibrous scaffolds. In optimum conditions (concentration of 8.15%, feeding rate of 0.2 mL/h, voltage of 18.50 kV and TCD of 13.0 cm), the minimum experimental fiber diameter was found to be 225 nm which was in good agreement with the predicted value by the BBD analysis (228 nm). In vitro drug release study of doxorubicin (DOX)‐loaded nanofibrous scaffolds, higher drug content induced an extended release of drug. Also, drug release rate was not dependent on drug/polymer ratio in different electrospun nanofibrous formulations. The equation of M_t = c₀ + kt^0.5was used to describe the kinetic data of DOX release from electrospun nanofibers. The cell viability of DOX‐loaded nanofibrous scaffolds was evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, a tetrazole assay on lung cancer A549 cell lines. We propose that DOX‐incorporated PLA/PEG/MWCNT nanofibrous scaffold could be used as a superior candidate for antitumor drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41286.     

Synthesis of hollow maghemite (-Fe2O3) particles for magnetic field and pH-responsive drug delivery and lung cancer treatment

The development of smart stimuli-responsive materials for drug delivery offers new opportunities for precise drug release and cancer chemotherapy. A combination of more than one stimuli is highly desirable to further maximize the therapy by taking the advantages of various unique merits. Herein, we employed polyethylene glycol (PEG) functionalized γ-Fe₂O₃ particles (γ-Fe₂O₃/PEG) as a novel magnetic drug carrier for doxorubicin (DOX) delivery. The results showed that the γ-Fe₂O₃/PEG exhibited excellent thermal effects under alternating magnetic field (AMF), high magneto-thermal stability, and large DOX loading capacity. Furthermore, the effects of pH and AMF on the DOX drug release were studied. It was discovered that DOX loaded γ-Fe₂O₃/PEG carriers were highly responsive to both AMF and pH, resulting in significantly improved cancer cell killing capability over a single stimulus. The magnetic and pH responsive drug delivery system provided a new opportunity to minimize the side effects and maximize the therapeutic efficiency of lung cancer treatment.     

Poly(Caprolactone)‐Poly(N‐Isopropyl Acrylamide)‐Fe3O4 Magnetic Nanofibrous Structure with Stimuli Responsive Drug Release

Poly(caprolactone; PCL)—poly(N‐isopropylacrylamie; PNIPAAm)—Fe₃O₄ fiber, that can be magnetically actuated, is reported. Here, a structure is engineered that can be utilized as a smart carrier for the release of chemotherapeutic drug via magneto‐thermal activation, with the aid of magnetic nanoparticles (MNPs). The magnetic measurement of the fibers revealed saturation magnetization values within the range of 1.2–2.2 emu g^?1. The magnetic PCL‐PNIPAAm‐Fe₃O₄ scaffold shows a specific loss power value of 4.19 W g^?1 at 20 wt% MNPs. A temperature increase of 40 °C led to a 600% swelling after only 3 h. Doxorubicin (DOX) as a model drug, demonstrates a controllable drug release profile. 39% ± 0.92 of the total drug loaded is released after 96 h at 37 °C, while 25% drug release in 3 h at 40 °C is detected. Cytotoxicity results show no significant difference in cell attachment efficiency between the MNP‐loaded fibers and control while the DOX‐loaded fibers effectively inhibited cell proliferation at 24 h matching the drug release profile. The noncytotoxic effect, coupled with the magneto‐thermal property and controlled drug release, renders excellent potential for these fibers to be used as a smart drug‐release agent for localized cancer therapy.     

Multifunctional zinc phthalocyanine-phenolic resin (ZnPc-PFR)@MSN nanocomposite based fluorescent imaging,photothermal therapy,and pH-sensitive drug release

Because of the good fluorescence of zinc phthalocyanine-phenolic resin (ZnPc-PFR) photosensitizer and large specific surface area of mesoporous silica nanoparticles (MSNs), a highly efficient nano-drug carrier system, denoted as ZnPc-PFR@MSN, was constructed for photothermal therapy (PTT) and pH-sensitive drug delivery. The facile hydrothermal reaction was used to synthesize ZnPc-PFR nanoparticles in one-step. After loading the as-synthesized ZnPc-PFR nanoparticles into MSNs, and a good high drug-loading rate (143.7 mg g⁻¹) to the anticancer drug of Adriamycin (DOX) could be obtained. Thus, a novel nanosphere with the merits of good fluorescence, high drug-loading rate (143.7 mg g⁻¹), better sustained-release properties, and photothermal properties (reached 43.23°C within 260 s) was prepared. The as-synthesized multifunctional composites make it a good candidate in fluorescence imaging, PTT, and drug delivery.     

PEGylated polylysine derived copolymers with reduction‐responsive side chains for anticancer drug delivery

Reduction‐responsive drug delivery systems have recently gained intense attention in intracellular delivery of anticancer drugs. In this study, we developed a PEGylated polypeptide, poly(ethylene glycol)‐block‐poly(?‐propargyloxycarbonyl‐l ‐lysine) (PEG₁₁₃‐b‐PPAL), as a novel clickable substrate for conjugation of reduction‐responsive side chains for antineoplastic drug delivery. PEG₁₁₃‐b‐PPAL was synthesized through ring‐opening polymerization of alkyne‐containing N‐carboxyanhydride monomers. A designed disulfide‐containing side chain was introduced onto the PEGylated polypeptide by click reaction. The obtained copolymer PEG₁₁₃‐b‐P(Lys‐DSA) formed micelles by self‐assembly, which exhibited reduction‐responsive behavior under the stimulus of 10 mmol L^–1 glutathione (GSH) in water. A small molecule intermediate, compound 2 , was used as a model to investigate the thiol reduction mechanism of PEG₁₁₃‐b‐P(Lys‐DSA) copolymers. The anticancer drug doxorubicin (DOX) was then loaded into the micelles with a drug loading content of 6.73 wt% and a loading efficiency of 40.3%. Both the blank and the drug‐loaded micelles (DOX‐loaded polylysine derived polymeric micelles (LMs/DOX)) adopted a spherical morphology, with average diameters of 48.0 ± 13.1 and 63.8 ± 20.0 nm, respectively. The in vitro drug release results indicated that DOX could be released faster from the micelles by the trigger of GSH in phosphate buffered saline. Confocal laser scanning microscopy and flow cytometer analysis further proved the intracellular delivery of DOX by LMs/DOX and their GSH‐sensitive release behavior. A 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay showed that the polymers exhibited negligible cytotoxicity towards normal L929 cells or cancer MCF‐7 cells with a treated concentration up to 1.0 mg mL^–1. In conclusion, our synthesized biocompatible and biodegradable PEGylated polypeptides hold great promise for intracellular antineoplastic drug delivery. © 2019 Society of Chemical Industry     

Stimuli-responsive Supra-biomolecular Nanoassemblies of Cucurbit[7]uril with Bovine Serum Albumin: Drug Delivery and Sensor Applications

Construction and characterization of stimuli-responsive supra-biomolecular nanoassembly between cucurbit[7]uril (CB7) and bovine serum albumin (BSA), uptake and release of doxorubicin (DOX) in live cells, the enhanced sensitivity of brilliant green (BG) and the metal ion-induced relocation of neutral red (NR) dye to BSA have been discussed in this review. The fluorescence intensity of DOX is largely quenched in the presence of nanoassembly which recovers with adamantylamine or by changing the pH of the solution, indicating the significant uptake and release of DOX. Whereas, the interaction of BG with CB7-BSA assembly leads to a huge fluorescence enhancement ∼350-fold through ternary complex formation. In another study, the supramolecular pK_a tuning of nanoassembly encapsulated NR dye with metal ion and the consequent relocation of NR from CB7 cavity to the hydrophobic pocket of BSA have been demonstrated. All these studies show promising applications in drug delivery and on-off sensor.     

A magnetic polypeptide nanocomposite with pH and near-infrared dual responsiveness for cancer therapy

A magnetic polypeptide nanocomposite with pH and near-infrared (NIR) dual responsiveness was developed as a drug carrier for cancer therapy, which was prepared through the self-assembly of Fe₃O₄ superparamagnetic nanoparticles, poly(aspartic acid) derivative (mPEG-g-PDAEAIM) and doxorubicin (DOX) in water. Fe₃O₄ nanoparticles were prepared to provide the superparamagnetic core of nanocomposites for tumor targeting via chemical co-precipitation. The protonable imidazole groups of mPEG-g-PDAEAIM with a pKa of ~7 were accountable for the pH-responsiveness of nanocomposites. The photothermal effect of nanocomposites under the irradiation of NIR laser was induced via the interactions between dopamine groups of mPEG-g-PDAEAIM and Fe₃O₄ superparamagnetic nanoparticles to trigger the drug release. NMR, FT-IR, TEM, hysteresis loop analysis and MRI were utilized to characterize the materials. The DOX loaded nanocomposites exhibited pH-responsive and NIR dependent on/off switchable release profiles. The nanocomposites without drug loading (Fe₃O₄@mPEG-g-PDAEAIM) showed excellent biocompatibility while DOX loaded nanocomposites caused MCF-7 cells’ apoptosis due to the photothermal/chemotherapy combination effects. Overall, the pH and near-infrared dual responsive magnetic nanocomposite had a great potential for cancer therapy.     

F3-functionalized nanoscale metal–organic frameworks for tumor-targeting combined chemotherapy and chemodynamic therapy

Nanoscale metal–organic frameworks (nMOFs) have attracted much attention as emerging porous materials as drug delivery carriers. Appropriate surface modification of them can greatly improve stability and introduce biocompatibility and cancer targeting functionality into drug delivery systems. Herein, we prepared nano-sized MIL-101(Fe)-N₃ and loaded anticancer drug doxorubicin (DOX) into it. The synthetic polymer layer Alkyne-PLA-PEG was then attached to the F3 peptide (labeled as Alkyne-PLA-PEG-F3), and the surface of DOX/MIL-101(Fe)-N₃ was covalently modified with it to obtain DOX/MIL-101-PLA-PEG-F3. Nano-sized MIL-101(Fe)-N₃ has high drug loading capacity and the modification of MIL-101(Fe)-N₃ by polymer Alkyne-PLA-PEG not only improved the dispersion, but also avoided the sudden release of the drugs and increased the biocompatibility of nanocarriers. The F3 peptide introduced into the nanocarriers also enabled it to specifically target tumor tissues and achieved active targeted drug delivery. As a nucleolin-mediated endocytosis drug delivery system, DOX/MIL-101-PLA-PEG-F3 can not only deliver anticancer drugs to tumors accurately, but also participate in Fenton-like reaction to generate hydroxyl radicals (•OH) for chemodynamic therapy (CDT), thus enabling combination therapy. It holds great promise as drug candidates to reduce systemic toxicity and improve the efficacy of cancer treatment.     

A Novel Stimuli-Responsive Magnetite Nanocomposite as De Novo Drug Delivery System

A novel stimuli-responsive magnetite nanocomposite as de novo drug delivery system for cancer chemotherapy is developed successfully through the incorporation of magnetite nanoparticles into PEG-b-(PNIPAAm-b-PAA)₂ copolymer. The chemical structures of samples were characterized using FTIR and ¹H NMR spectroscopies. Furthermore, thermal property, morphology, size, and magnetic properties of the nanocomposite were investigated. The DOX loading and encapsulation efficiencies as well as stimuli-responsive drug release ability of the nanosystem were studied. As results, at pH 5.3 and temperature of 41°C the nanocomposite exhibited higher drug release values, which qualified it for cancer chemotherapy according to especial features of cancerous tissue.     

ABC block copolymer as “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs

Amphiphilic triblock copolymer of poly(ethylene glycol)-block-poly(dimethylaminoethyl methacrylate)-block-poly(ε-caprolatone) (PEG-PDMA-PCL) was synthesized using a one-pot sequential oxyanionic polymerization of DMA and ε-CL, associated with a PEG-O⁻K⁺ macroinitiator. The pH-responsive micellization behavior of the copolymer was studied using dynamic light scattering (DLS), steady-state fluorescence and TEM techniques. The anti-cancer drug of doxorubicin (DOX) was chosen as a model drug to investigate the potential application of this triblock copolymer in drug controlled release. The results indicated the important roles of the PCL block for drug loading, the PDMA block for pH-responsive release, and PEG block for good bio-affinity. Cell cytotoxicity tests showed that the DOX-loaded PEG-PDMA-PCL micelles were pharmaceutically active to suppress the growth of SKOV-3 cells. This novel stimuli-responsive block copolymer is an attractive candidate as the “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs.     

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

In order to obtain a pH‐sensitive delivery carrier for doxorubicin (DOX), DOX‐loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU‐COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, ¹H NMR spectroscopy, gel permeation chromatography, UV–visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (?1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug‐loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH‐sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit‐8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF‐7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis‐inducing effects on MCF‐7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl‐2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real‐time polymerase chain reaction (PCR) assay and western blot assay. © 2018 Society of Chemical Industry     

GSH-responsive polyglutamic acid nanocarriers for dual targeted cancer therapy

In order to reduce the toxic side effects of chemotherapeutic drugs and improve the targeting and efficiency of cancer treatment, the development of drug delivery system has received great attention. In this study, second generation polyglutamic acid dendrimers (G₂) are used as basic materials to produce porous nanoparticles through cross link by crosslinkers containing disulfide bonds. The crosslinked products (G₂)_n have negative electricity and abundant voids, which enable them to adsorb the electronegative anticancer drug DOX. At the same time, in order to transport DOX to the tumor site, we modified FA on DOX and encapsulated it in magnetic mesoporous silica (FA-DOX-MSNs). Therefore, the final nanoparticles (FA-DOX-MSNs/(G₂)_n) not only have dual targeting ability to transport DOX to the tumor site, but also have reductive responsiveness that can release drugs responsively in the tumor cells. In addition, it has good biocompatibility and endocytosis ability.     

PEGylated hollow pH‐responsive polymeric nanocapsules for controlled drug delivery

Novel pH‐responsive PEGylated hollow nanocapsules (HNCaps) were fabricated through a combination of distillation–precipitation copolymerization and surface thiol–ene ‘click’ grafting reaction. For this purpose, SiO₂ nanoparticles were synthesized using the Stöber approach, and then modified using 3‐(trimethoxysilyl)propyl methacrylate (MPS). Afterward, a mixture of triethyleneglycol dimethacrylate (as crosslinker), acrylic acid (AA; as pH‐responsive monomer) and MPS‐modified SiO₂ nanoparticles (as sacrificial template) was copolymerized using the distillation–precipitation approach to afford SiO₂@PAA core–shell nanoparticles. The SiO₂ core was etched from SiO₂@PAA using HF solution, and the obtained PAA HNCaps were grafted with a thiol‐end‐capped poly(ethylene glycol) (PEG) through a thiol–ene ‘click’ reaction to produce PAA‐g‐PEG HNCaps. The fabricated HNCaps were loaded with doxorubicin hydrochloride (DOX) as a model anticancer drug, and their drug loading and encapsulation efficiencies as well as pH‐dependent drug release behavior were investigated. The anticancer activity of the drug‐loaded HNCaps was extensively evaluated using MTT assay against human breast cancer cells (MCF7). The cytotoxicity assay results as well as superior physicochemical and biological features of the fabricated HNCaps mean that the developed DOX‐loaded HNCaps have excellent potential for cancer chemotherapy. © 2020 Society of Chemical Industry     

Bioinspired photo-degradable amphiphilic hyperbranched poly(amino ester)s: Facile synthesis and intracellular drug delivery

A novel amphiphilic photo-degradable hyperbranched polymer was reported at the first time. The hyperbranched o-nitrobenzyl containing poly(amino ester)s (HPAE) were prepared by one-pot Michael addition polymerization. The photo-induced degradation of hyperbranched poly(amino ester)s was confirmed by gel permeation chromatography (GPC) and UV-vis spectra. Bioinspired phosphorylcholine grafted HPAE (HPAE-PC) was synthesized via thiol-ene click chemistry. HPAE-PC can self-assemble to micelles and the micelles could be disassembled under UV irradiation because of the photo-degradation of HPAE. HPAE-PC micelles were used to load anticancer drug Doxorubicin (DOX). In vitro drug release studies showed that the release of DOX was much faster in the presence of UV irradiation than that without UV irradiation. The fluorescence microscope results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Moreover, the DOX-loaded HPAE-PC micelles under UV irradiation exhibited better anticancer activity against A549 cells than that of the nonirradiated ones. The novel amphiphilic photo-degradable hyperbranched polymers can be used to construct spatiotemporal on-demand drug delivery system for cancer therapy.     

PEG and PEG-peptide based doxorubicin delivery systems containing hydrazone bond

mPEG and mPEG-peptide based drug delivery systems were prepared by conjugating doxorubicin (DOX) to these carrier molecules via hydrazone bond. The peptide, AT1, with a sequence of CG₃H₆G₃E served as mPEG and doxorubicin attachment site. Histidines were incorporated to the sequence to improve pH responsiveness of the carrier molecule. Hydrodynamic diameters (mean sizes) of mPEG-based drug delivery system (mPEG-HYD-DOX) were measured as 9?±?0.5 and 7?±?0.5 nm at pH 7.4 and pH 5.0, respectively. Mean size of the aggregates of the peptide containing drug delivery system, mPEG-AT1-DOX, was determined as 12?±?2 nm at neutral pH. At pH 5.0, on the other hand, mPEG-AT1-DOX exhibited a size distribution between 20 and 100 nm centered at about 40 nm. Comparison of % DOX release values of the drug delivery systems obtained at pH 7.4 and pH 5.0 indicated that mPEG-AT1-DOX has enhanced pH sensitivity. DOX equivalent absolute IC₅₀ values were obtained as 0.96?±?0.51, 21.9?±?5.9, and 5.55?±?0.75 μg/mL for free DOX, mPEG-HYD-DOX, and mPEG-AT1-DOX, respectively. Considering more pronounced pH sensitivity and cytotoxicity of mPEG-AT1-DOX, the use of both pH responsive functional groups and acid cleavable chemical bond between the carrier molecule and drug can be a promising approach in the design of drug delivery systems for cancer therapy.     

Facile synthesis of up-conversion Cit-NaYF4:Yb,Tm @phenol-formaldehyde resin@Ag composites for the sensitive detection of S2−

In this work, we synthesized the core-shell structure citric acid-modified up-conversion luminescent nanoparticles (Cit-NaYF₄:Yb,Tm) (denoted as UC)@ polymer of phenol-formaldehyde resin (PFR) particles. Ag nanoparticles were successfully loaded onto the PFR's shell by direct reduction of AgNO₃ in situ with rich hydroxyl groups in PFR and a new application of the UC@PFR@Ag composites for detection of S²⁻ was investigated. A good linear relationship between the fluorescence intensity of as-synthesis of UC@PFR@Ag composites and the concentration of S²⁻ could be found within the range of 2–100 nM (R² = 0.9929) with a limit of detection of 0.67 nM. The values of S²⁻ content in actual water samples obtained with the proposed method are much closer to unity as compared to the corresponding values obtained with the UV method.     

Membranes of cellulose triacetate produced from sugarcane bagasse cellulose as alternative matrices for doxycycline incorporation

Cellulose triacetate (CTA) membranes were prepared using polyethylene glycol, 600 g mol^?1, (PEG) as additive and were utilized in essays of doxycycline (DOX) incorporation using two different procedures: (i) incorporation of the drug during the membrane preparation and (ii) incorporation of the drug to a previously prepared membrane. In the first, the produced membrane presented high compatibility between DOX and CTA, what was evidenced by analyzing the DSC curve for a CTA/PEG 50%/DOX system. Results showed that the drug is homogeneously distributed throughout the matrix, molecularly. In the second method, the drug was molecularly and superficially adsorbed, as seen through the DSC curve for the system CTA/PEG 10%/DOX, which nearly does not present alterations in relation to the original material, and through the isotherm of drug adsorption that follows the Langmuir model. Results showed that the membranes produced from sugarcane bagasse are adequate to produce matrices for drug‐controlled release, both for enteric use (Method (i)) and topic use (Method (ii)). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Functionalized bacterial cellulose nanowhiskers as long‐lasting drug nanocarrier for antibiotics and anticancer drugs

A nano drug carrier based on sustainable and biocompatible nanocellulose was developed for use in prolonged drug releases. The grafting of β‐cyclodextrin (βCD) on bacterial cellulose nanowhiskers (BCNC) using citric acid (CA) as a green linker was performed. This led to the formation of functionalized BCNC‐grafted‐βCD (BCNC‐g‐βCD). Broad‐spectrum antibiotic Ciprofloxacin (CIP) and anticancer drugs Doxorubicin (DOX) and Paclitaxel (PTX) were used as model drugs. These model drugs were conjugated to BCNC‐g‐βCD to form the drug‐nanocarrier systems (BCNC‐g‐βCD‐drug). The change in the nanowhiskers’ surface chemistry, morphology, and crystallinity was characterized by FTIR, solid‐state ¹³C NMR, scanning electron microscopy (SEM), atomic force microscopy (AFM), and x‐ray diffraction (XRD). The functionalized nanowhiskers showed a significant increase in the drug payloads, which ranged from 495 ±4–810 ±7 μg/mg, along with a radical improvement in the drug release profiles. For all of the developed drug‐conjugated nanocarriers, the initial burst releases were reduced effectively. The observed drug releases showed a sustained and controlled manner, with cumulative releases of 75–90 % over 5–5.5 days. Nevertheless, an improved drug release performance was observed in the acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data were fitted zero‐order kinetic model with drug release constants (K₀) of 0.68, 0.74, and 0.79 μg drug/h (at pH 6.4 and 37 °C) for BCNC‐g‐βCD‐CIP, BCNC‐g‐βCD‐DOX, and BCNC‐g‐βCD‐PTX nanosystems, respectively. The observed higher payloads along with the slow releases of drugs from the developed nanocarrier suggests its promising potential for reducing the frequent daily dosing and minimizing systemic toxicity of loaded drugs.     

Silver-doped biphasic calcium phosphate/alginate microclusters with antibacterial property and controlled doxorubicin delivery

Biphasic calcium phosphate (BCP) based materials possessed with both excellent biocompatibility and antibacterial activity show potential advantages for biomedical applications. Here, the silver-doped BCP/Alginate (_AgBA) microclusters were first fabricated using the double-emulsions method. First, BCP nanoparticles were incorporated into the alginate network to form BCP/Alginate microclusters via the emulsion process. Then, silver nanoparticles (AgNPs) were in situ involved in BCP/Alginate networks to obtain the final _AgBA microclusters. Transmission electron microscopy and scanning electron microscopy confirmed that BCP nanoparticles and AgNPs were uniformly distributed in _AgBA microclusters. The morphology of _AgBA microclusters could be regulated by adjusting emulsion power, and microclusters using the medium powder (500 W) showed a regular spherical shape. Furthermore, CCK-8 analysis identified that _AgBA microclusters were cytocompatible culturing with human bone marrow-derived mesenchymal stem cells. Qualitative antibacterial tests exhibited the excellent inhibition effects of _AgBA microclusters against Staphylococcus aureus (Gram-positive) and Escherichia coli. (Gram-negative). Lastly, the doxorubicin (DOX)-loaded _AgBA microclusters presented adjustable loading efficiency of DOX and controllable release profiles. The cumulative release could reach 73.3% after 72 h in PBS. The above results raised a new route for antibacterial microclusters development for biomedical applications.