Thermo-responsive Drug Release Research Articles

Co-delivery of carboplatin and doxorubicin using ZIF-8 coated chitosan-poly(N-isopropyl acrylamide) nanoparticles through a dual pH/thermo responsive strategy to breast cancer cells

A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.6 % and 55.54 %, respectively. NPs showed a pH and thermoresponsive drug release profile with a sustained prolonged release under physiological conditions. The in vitro cytotoxicity experiments showed a significant synergism of CBP and DOX to induce the IC50 of 1.96 μg/mL in MCF-7 cells and 4.54 μg/mL in MDA-MB-231 cells. Also, the final NPs were safer than free DOX and CBP on normal cells. The in vitro study confirmed the higher potency of the designed NPs in combination therapy against breast cancer cells with lower side effects than free drugs.

MXene/TPU Hybrid Fabrics Enable Smart Wound Management and Thermoresponsive Drug Delivery.

Thermoresponsive wound dressings with real-time monitoring and on-demand drug delivery have gained significant attention recently. However, such smart systems with stable temperature adjustment and drug release control are still lacking. Here, a novel smart fabric is designed for wound management with thermoresponsive drug delivery and simultaneously temperature monitoring. The triple layers of the fabrics are composed of the drug-loaded thermoresponsive nanofiber film, the MXene-optimized joule heating film, and the FPCB control chip. The precise and stable temperature stimulation can be easily achieved by applying a low voltage (0-4 V) to the heating film, achieving the temperature control ranging from 25 to 130 °C. And the temperature of the wound region can be monitored and adjusted in real time, demonstrating an accurate and low-voltage joule heating capability. Based on that, the drug-loaded film achieved precise thermoresponsive drug release and obtained significant antibacterial effects in vitro. The in vivo experiments also proved the hybrid fabric system with a notable antibacterial effect and accelerated wound healing process (about 30% faster than the conventional gauze group).

Nanocellulose-Reinforced 4D Printed Hydrogels: Thermoresponsive Shape Morphing and Drug Release

Nanocellulose-Reinforced 4D Printed Hydrogels: Thermoresponsive Shape Morphing and Drug Release

Biodegradable pectin-based thermo-responsive composite GO/hydrogel with mussel inspired tissue adhesion for NIR enhanced burn wound healing

Thermo-responsive hydrogels with biodegradability have great application in biomedical areas, while the Poly(N-isopropylacrylamide) (PNIPAM) based hydrogels exhibiting lower critical solution temperature (LCST) around body temperature have shown promising applications in diverse areas such as drug delivery, tissue engineering, and wound repairing. In this study, PNIPAM based thermo-responsive copolymer with ketone functional group was polymerized and the LCST was regulated to body temperature, then biodegradable self-healing hydrogels with injectability were fabricated by cross-linking the thermo-responsive copolymers with dopamine functionalized pectin hydrazide (PDAH). The hydrogel exhibited good mechanical strength, excellent biocompatibility and thermo-responsive sustained drug release process. The nano-graphene oxide (GO) was incorporated to design near-infrared (NIR) sensitive nanocomposite hydrogel to serve as photothermal enhanced wound dressing with vancomycin loading. The composite hydrogel also showed pH-responsive drug release behavior and the NIR irradiation also accelerated the release rate based on photothermal induced phase transition. More importantly, the nanocomposite hydrogel with vancomycin loading and photothermal property can promoted burn wound repairing rate by inhibiting the bacterial growth. As a result, this GO composite hydrogel (GO/hydrogel) could act as NIR triggered photo-thermal enhanced drug delivery platform for promoted wound repairing in the near future.

Biocompatible Anisole-Nonlinear PEG Core-Shell Nanogels for High Loading Capacity, Excellent Stability, and Controlled Release of Curcumin.

Curcumin, a nontoxic and cheap natural medicine, has high therapeutic efficacy for many diseases, including diabetes and cancers. Unfortunately, its exceedingly low water-solubility and rapid degradation in the body severely limit its bioavailability. In this work, we prepare a series of biocompatible poly(vinyl anisole)@nonlinear poly(ethylene glycol) (PVAS@PEG) core-shell nanogels with different PEG gel shell thickness to provide high water solubility, good stability, and controllable sustained release of curcumin. The PVAS nanogel core is designed to attract and store curcumin molecules for high drug loading capacity and the hydrophilic nonlinear PEG gel shell is designed to offer water dispersibility and thermo-responsive drug release. The nanogels prepared are monodispersed in a spherical shape with clear core-shell morphology. The size and shell thickness of the nanogels can be easily controlled by changing the core-shell precursor feeding ratios. The optimized PVAS@PEG nanogels display a high curcumin loading capacity of 38.0 wt%. The nanogels can stabilize curcumin from degradation at pH = 7.4 and release it in response to heat within the physiological temperature range. The nanogels can enter cells effectively and exhibit negligible cytotoxicity to both the B16F10 and HL-7702 cells at a concentration up to 2.3 mg/mL. Such designed PVAS@PEG nanogels have great potential to be used for efficient drug delivery.

Dual pH-/Thermoresponsive Shell-Cross-Linked Magnetic Mesoporous Nanospheres for Doxorubicin Delivery and In Vitro/In Vivo Cancer Treatment

Engineered nanomaterials have been explored for chemotherapeutic drug delivery systems toward improved therapeutic effects. In this study, magnetic nanospheres consisting of MCM-41 formed onto iron oxide nanoparticles (MIO NPs) to form MMCM with cross-linked shells of Pluronic F127 (PF) and polyethylenimine (PEI) to form (MMFPEI NSs) nanospheres were synthesized. These nanospheres were loaded with doxorubicin (DOX) anticancer drug for drug-controlled release and therapeutic efficacy evaluations in mice. Nanoscale/core–shell MMFPEI NSs were successfully formed as indicated by the TEM analysis. The microstructural analysis revealed the presence of three peaks corresponding to indexed reflections (100), (110), and (200) of MCM-41. The MMFPEI NSs displayed a pH-/thermoresponsive drug release of 84.76% under a simulated tumor microenvironment. Principally, the Peppas-Sahlin, Weibull, and Korsmeyer-Peppas models, respectively, provided the best fitting for our drug delivery system with the highest correlation degree of coefficient (R2) and the lowest AIC. The kinetics studies for diffusion exponent indicated that the MMFPEI NSs possessed predominantly Fickian diffusion behavior. The growth retardation results of HepG2 cells showed that when compared with free DOX, the MMFPEI-DOX NSs exhibited statistically significant stronger cell inhibition efficacy at the dosages of 2, 5, and 10 μg/mL after 24 and 48 h of incubation. According to the in vivo therapeutic assessments, the tumor sizes upon inoculation with PBS, MMFPEI NSs, PBS-DOX, and MMFPEI-DOX NSs were 1302.7, 1165.6, 830.9, and 382.6 mm3, respectively. Therefore, the formulated nanospheres have great probable for drug delivery in cancer therapy to overcome the limits of traditional chemotherapy.

Dual-functional MOFs-based hybrid microgel advances aqueous lubrication and anti-inflammation

This paper demonstrates the hybridization of copolymer microgel with drug-loaded metal–organic frameworks nanoparticles that can achieve excellent aqueous lubricating performance and anti-inflammatory effect for synergistic treatment of osteoarthritis (OA). Poly(ethylene glycol)-graft-poly(N-isopropylacrylamide) (PEG-g-PNIPAm) microgel layer is grown on the MIL-101(Cr) surface via one-pot soap-free emulsion polymerization method. The lower critical solution temperature of the MIL-101(Cr)@PEG-g-PNIPAm hybrid is raised significantly by incorporating PEG chains into the PNIPAm microgel matrix, which greatly enhances the high-temperature aqueous dispersion stability. The hybrid microgel demonstrated reversibly thermo-sensitive swelling-collapsing behavior to modulate the optical properties and hydrodynamic size. Using as aqueous lubricating additives, the hybrid reduces over 64% and 97% in friction coefficient and wear volume. Also, the hybrid supports desirable temperature-controlled lubrication modulation due to their reversible thermo-responsive behavior, which is benefit to joint lubrication of OA. After encapsulating anti-inflammatory diclofenac sodium (DS), the DS-MIL-101(Cr)@PEG-g-PNIPAm shows thermo-responsive drug release in aqueous media, which can improve the drug-delivery efficiency. By co-culturing the DS-loaded hybrid with human normal chondrocytes, we demonstrate good biocompatibility and anti-inflammatory effect on the chondrocytes with inflammation by regulating the expression of OA-related genes and proteins. Our work establishes multifunctional MOFs-based hybrid microgel systems for advanced colloids modulation and biomedical application.

Thermo-responsive release of diclofenac sodium from poly (ε-caprolactone)/glyceryl trilaurate co-continuous composite prepared by heat treatment

Nowadays, it is still a tough challenge to prepare thermo-responsive drug delivery system without the use of poly(N-isopropylacrylamide) (PNIAPAM) and its derivatives. Herein, we attempted to fabricate a novel co-continuous composite with thermo-responsive drug release behavior induced by the phase transition of dispersed phase. Poly (ϵ-caprolactone) (PCL) scaffold with connected porous structure was prepared first, followed by the introduce and impregnating of diclofenac sodium/glyceryl trilaurate (DS/C12) hot melt mixture. After solidification at 25 °C, PCL/C12 composites with co-continuous structure were obtained. The connected porous structure of PCL scaffold and morphology of PCL/C12 composites were confirmed by scanning electron microscope. The thermo-responsive drug release mechanism of PCL/C12 composites was investigated by differential scanning calorimeter and two-dimensional infrared correlation spectroscopy. The results indicated that the temperature of onset melting and melting point of C12 was about 41.5 °C and 47.5 °C, respectively. When the temperature was switched from 37 °C to 45 °C, C12 underwent a melt transition, and the regular aggregation of C12 molecular chain was disrupted, accelerating the release of DS. The in vitro release results presented that PCL/C12 composites could achieve on-off controlled release of DS under alternative temperature of 45 °C and 37 °C. According to the comprehensive test results, this PCL/C12 composites should have promising application in bone tissue engineering. Schematic diagram illustrating of the preparation of poly (ϵ-caprolactone)/glyceryl trilaurate (PCL/C12) co-continuous composite (a) and its on-off controlled release behavior of diclofenac sodium (DS) under alternative temperature of 45 °C and 37 °C (b and c). • Poly (ϵ-caprolactone)/glyceryl trilaurate (PCL/C12) co-continuous composite was fabricated. • PCL/C12 composite achieved on-off controlled release of diclofenac sodium under alternative temperature of 45 °C and 37 °C. • The controlled drug release behavior of PCL/C12 composite was induced by the phase transition of C12. • This thermo-responsive composite was prepared without the use of poly(N-isopropylacrylamide) and its derivatives. • This work provided a promising strategy and method for the preparation of thermo-responsive drug delivery systems.

The effect of formulation morphology on stimuli-triggered co-delivery of chemotherapeutic and MRI contrast agents

Most conventional chemotherapeutics have narrow therapeutic windows, and thus their delivery remains challenging and often raises safety and efficacy concerns. Theranostic platforms, with simultaneous encapsulation of therapeutic and diagnostic agents, have been proposed as next-generation formulations which can overcome this issue. In this work, we used electrohydrodynamic approaches to fabricate core@shell formulations comprising a pH responsive Eudragit L100 shell embedded with superparamagnetic iron oxide nanoparticles (SPIONs), and a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)/ethyl cellulose core loaded with the model drug carmofur. By varying the weight ratio of core polymer to shell polymer, the morphology of PNIPAM/ethyl cellulose@Eudragit L100 microparticles could be changed from concave to spherical. Smooth cylindrical fibres could also be generated. All the formulations exist as amorphous solid dispersions of drug-in-polymer, with distinct core@shell architectures. The fibres have clear thermo-responsive drug release profiles, while no thermo-responsive properties can be seen with the particles. All the formulations can protect SPIONs from degradation in gastric fluids (pH ∼ 1.5), and around the physiological pH range the materials offer effective and pH-responsive relaxivity. The r2 values also display clear linear relationships with drug release data, suggesting the potential of using MRI signals to track drug release in vivo. Mathematical equations were established to track drug release in vitro, with very similar experimental and predicted release profiles obtained.

Near-Infrared Laser-Responsive Photothermal Bubble-Generating PLA Nanoparticles for Controlled Drug Release

Stimuli-responsive drug delivery systems can respond to specific external stimuli, resulting in improved treatment outcomes and reduced side effects from their controllable site-specific release ability. The aim of this study was to develop a thermo-responsive bubble-generating drug release platform by near-infrared (NIR) laser irradiation using melanin-perfluorohexane-methotrexate-polylactic acid (Mel @PFH@MTX-PLA) nanoparticles. Mel@PFH@MTX-PLA nanoparticles were successfully prepared without precipitation or aggregation. By adjusting the amount of perfluorohexane (PFH), a size of Mel@PFH@MTX-PLA nanoparticles with optimal conditions was about 52.75 ± 1.41 nm. Due to the photothermal conversion properties of melanin, the temperature of the Mel@PFH@MTX-PLA nanoparticles was increased to about 59.2 °C after 7 min of 808 nm NIR laser irradiation at a power density of 1.5 W/cm2. The NIR laser-induced temperature increase triggered additional drug release and caused the phase transition of PFH, resulting in dramatic bubble generation. The resultant Mel@PFH@MTX-PLA nanoparticles can be utilized in biomedical applications as promising carriers for localized and controlled drug delivery.

Thermoresponsive magnetoliposome encapsulating doxorubicin and high performance Ferumoxytol for effective tumor synergistic therapy in vitro

Owing to the multiple pathogenic routes and enormous proliferative capacity of tumor cells, conventional drug carriers find it difficult to fulfill clinical treatment gradually, for instance liposomes with single chemotherapy mode. New nanodrug carriers capable of multimodal therapy have emerged in an attempt to find an effective treatment; however, very few of them could be approved eventually, mainly because they could not reach the strict pharmaceutical quality standards. In this context, high-performance liposome synthesis based on typical medical materials may be an effective resolution strategy. Herein, a novel magnetoliposome coencapsulating doxorubicin and iron oxide nanomedicine Ferumoxytol was designed. After the formulation process screening, the magnetoliposome was found to be in stable dispersion with high Doxorubicin payload. In particular, a prominent magnetocaloric effect and thermoresponsive drug release profile were obtained. This is due to the combination of high performance Ferumoxytol with thermosensitive phospholipids dipalmitoylphosphatidylcholine. Compared with single hyperthermia or single chemotherapy, the chemotherapy and magnetic hyperthermia dual-modal synergetic treatment of the magnetoliposome present distinct advantages on cell viability assay in vitro. The novel temperature stimuli-responsive liposome enriches the anti-cancer nanomedicine species available in clinics, motivating the development of the clinical treatment strategy.

Peptidic Monodisperse PEG "Comb" as Multifunctional "Add-On" Module for Imaging-Traceable and Thermo-Responsive Theranostics.

Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a 19 F magnetic resonance imaging (19 F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high 19 F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot" 19 F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.

Polydopamine-Based "Four-in-One" Versatile Nanoplatforms for Targeted Dual Chemo and Photothermal Synergistic Cancer Therapy.

The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.

Conjugated Polymers-Based Thermal-Responsive Nanoparticles for Controlled Drug Delivery, Tracking, and Synergistic Photodynamic Therapy/Chemotherapy.

Stimuli-responsive multifunctional nanomaterials have attracted much attention due to drug release on-demand for cancer therapy. In this study, the thermal-responsive nanoparticles are prepared based on cationic conjugated poly(fluorene-co-vinylene) (PFV), temperature-responsive poly(N-isopropylacrylamide) (PNIPAM), and antitumor model drug doxorubicin (DOX). Interestingly, the nanoparticles possess multiple functions including thermoresponsive drug release, cell imaging, and chemo- and photodynamic synergistic therapy. The drug is released efficiently above the lower critical solution temperature (LCST) of PNIPAM, and more than 70% of the loaded drugs were delivered at pH 5.5 and 37 °C. Importantly, the drug release process can be tracked by fluorescent imaging owing to the bright fluorescence of conjugated polymer-based nanoparticles. Specifically, conjugated polymer PFV acts as a photosensitizer to produce high reactive oxygen species under white light irradiation, bringing an effective chemo-/photodynamic therapy (PDT) synergistic effect. The cell viability of MCF-7 decreases to only 3.2% after treating with PNIPAM-DOX-CPNs (conjugated polymer nanoparticles) under white irradiation, which is much lower than that with a single treatment. Therefore, the multifunctional nanoparticles provide a promising platform for controllable drug delivery, tracking, and tumor therapy in biomedical applications.

Controlled drug release from PNIPAM-incorporated melanin nanovesicles by photo-stimulation

ABSTRACTTo minimize side effects and increase drug efficacy, a novel strategies are needed to facilitate rapid drug release at the lesion site. In this study, a nanovesicle composed of phospholipids including melanin, poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM) and 5-fluorouracil (5-FU) is suggested for thermoresponsive drug release by near-infrared (NIR) laser irradiation. The novel aspect of the nanovesicles is the use of melanin, which has excellent biocompatibility. The nanovesicle was 180.4 ± 1.6 nm in size and stable for 1 week. After exposure to NIR laser, the temperature of the nanovesicle solution was increased above 51°C by the photothermal effect of melanin. The rate of 5-FU release from the nanovesicle was increased by about 14% for 12 h, following exposure to the laser irradiation compared with no such exposure. The drug release rate was increased depending on the amount of PNIPAM. Consequently, the nanovesicle has a potential application in NIR laser-responsive drug release.

Biogenic Cluster-Encased Gold Nanorods as a Targeted Three-in-One Theranostic Nanoenvelope for SERS-Guided Photochemotherapy against Metastatic Melanoma

Effective treatment of malignant melanoma requires an appropriate combination of therapeutic intervention with long-term prognosis as it often survives by monotherapies. Herein, we report a novel melanoma-targeted theranostic nanoenvelope (MTTNe: ISQ@BSA-AuNC@AuNR@DAC@DR5) which has been constructed by assembling a bovine serum albumin (BSA) stabilized gold nanocluster on a gold nanorod (BSA-AuNC@AuNR), a three-in-one theranostic modality, i.e., photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, tethered with a surface-enhanced Raman scattering (SERS) detection technique. The resultant MTTNe was coloaded with the melanoma-specific FDA approved drug dacarbazine (DAC) and a newly synthesized near-infrared (NIR) absorbing squaraine molecule ISQ that served partly as a photosensitizer and multiplex Raman reporter. Finally, a nanoenvelope was anchored with anti-DR5 monoclonal antibodies as a targeting motif for highly expressed melanoma-specific death receptors in malignant cells. Significant phototherapies of MTTNe were initiated upon an 808 nm single laser trigger which showed a synergistic effect of photothermal hyperthermia as well as singlet oxygen (1O2) driven photodynamic effect in the presence of ISQ followed by on-demand thermoresponsive drug release in the intracellular milieu. Moreover, a multiplex SERS spectral pattern of ISQ (1345 cm-1) and DAC (1269 cm-1) has been utilized for monitoring precise drug release kinetics and target-specific recognition on melanoma cells by Raman imaging. Therapeutic performance of the nanoenvelope was evaluated by in vitro cytotoxicity studies in human melanoma cells (A375) and confirmed the apoptotic phenomenon by molecular-level monitoring of intracellular SERS fingerprints. Finally, to address the biocompatibility of MTTNe, in vivo subacute toxicity was conducted on BALB/c mice. Hence, the current studies mark a footstep of a facile strategy for the treatment of melanoma by synergistic multimodal photothermal/photodynamic/chemotherapy.

Thermoresponsive polymer nanocarriers for biomedical applications.

Polymer nanocarriers allow drug encapsulation leading to fragile molecule protection from early degradation/metabolization, increased solubility of poorly soluble drugs and improved plasmatic half-life. However, efficiently controlling the drug release from nanocarriers is still challenging. Thermoresponsive polymers exhibiting either a lower critical solution temperature (LCST) or an upper critical solution temperature (UCST) in aqueous medium may be the key to build spatially and temporally controlled drug delivery systems. In this review, we provide an overview of LCST and UCST polymers used as building blocks for thermoresponsive nanocarriers for biomedical applications. Recent nanocarriers based on thermoresponsive polymer exhibiting unprecedented features useful for biomedical applications are also discussed. While LCST nanocarriers have been studied for over two decades, UCST nanocarriers have recently emerged and already show great potential for effective thermoresponsive drug release.

Microfluidic fabrication of biocompatible poly(N-vinylcaprolactam)-based microcarriers for modulated thermo-responsive drug release.

Various thermo-responsive polymers have been developed for controlled drug delivery upon the local application of external heat. The development of thermo-responsive polymers with high biocompatibility and tunable thermo-sensitivity is crucial for safe and efficient therapeutic application. In this study, thermo-responsive drug carriers featuring tunable thermo-sensitivities were synthesized using biocompatible poly(N-vinyl caprolactam) (PVCL) and stop-flow lithography. The PVCL-based particles showed selective drug release depending on temperature, illustrating their feasibility for on-demand controlled drug delivery. The volume phase transition temperature (VPTT) of the PVCL-based particles can be adjusted to vary from room temperature to body temperature by controlling their monomer compositions. In addition, modulated drug release was achieved by constructing multicompartments of different thermo-sensitivities within the PVCL particles. To accomplish thermo-responsive anticancer therapy, doxorubicin (DOX) was encapsulated into the PVCL particles as an anticancer drug. The DOX-loaded PVCL particles exhibited both thermo-responsive drug release and anticancer activity. This study demonstrates that thermo-responsive PVCL particles are highly promising carriers for safe and targeted anticancer therapy.

Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies.

Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic temperatures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid–liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (<200 nm), and enhanced physicochemical stability (Fourier transform infrared spectroscopy analysis). We observed a sustained release pattern (22%–34%) at 37°C (5 hours). On the other hand, >90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid–liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%–78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting.

Rheological analysis of hybrid hydrogels during polymerization processes

Abstract Development of new implant coatings with temperature-controlled drug release to treat infections after device implantation can be triggered by highly elastic hydrogels with adequate stability and adhesive strength in the swollen state. By using an ionic liquid (IL [ViPrIm]+[Br]−) as additive to N-isopropylacrylamide (NIPAAm) unique effects on volumetric changes and mechanical properties as well as thermoresponsive drug release of the obtained hybrid hydrogels were observed. In this context, rheological measurements allow the monitoring of gelation processes as well as chemical, mechanical, and thermal treatments and effects of additives. Hybrid hydrogels of pNIPAAm and poly (ionic liquid) (PIL) were prepared by radical emulsion polymerization with N,N′-methylenebis(acrylamide) as 3D crosslinking agent. By varying monomer, initiator and crosslinker amounts the multi-compound system during polymerization was monitored by oscillatory time sweep experiments. The time dependence of the storage modulus (G′) and the loss modulus (G″) was measured, whereby the intersection of G′ and G″ indicates the sol-gel transition. Viscoelastic behavior and complex viscosity of crosslinked and non-crosslinked hydrogels were obtained. Within material characterization rheology can be used to determine process capability and optimal working conditions. For biomedical applications complete hydrogelation inter-connecting all compounds can be received providing the possibility to process mechanically stable, swellable implant coatings or wound closures.