Nanoprecipitation Method Research Articles

Baicalin-Loaded Lipid-Polymer Hybrid Nanoparticles Inhibiting the Proliferation of Human Colon Cancer: Pharmacokinetics and In Vivo Evaluation.

This research work is focused on pharmacokinetic and biochemical experiments to assess baicalin-loaded lipid-polymer hybrid nanoparticles (LPHNPs) with colon-targeting specificity. The nanoprecipitation method was used to develop the LPHNPs, and the characterized formulation revealed the 184.3 nm particle size, PDI of 0.177, spherical shape, and zeta potential of -19.8 mV. The baicalin LPHNPs are said to be poorly absorbed in the stomach and small intestine, and in vitro drug release tests have shown that the drug is released mostly in the caecal fluid. Additionally, the LPHNPs showed stability and nonsignificant drug loss at 25 °C for 3 months. The least viable population of baicalin-loaded LPHNPs was detected at a lower IC50 value after 48 h, and no cytotoxicity was observed by blank suspension and blank LPHNPs up to the concentration of 100 µg/mL. Apart from this, the pharmacokinetics study showed that baicalin from LPHNPs is much less absorbed and least available in the blood plasma and maximum available in the colon. Concurrently, organ distribution studies demonstrated that baicalin-loaded LPHNPs were distributed more widely in the colon compared to baicalin suspension. Moreover, baicalin-loaded LPHNPs were found to be superior to a baicalin suspension in reducing elevated liver enzyme levels. In a nutshell, baicalin-loaded LPHNPs show superior efficacy and can be maximally localized into the colon rectal cancer along with systemic availability of the drug.

Study of the Chemical Profile and Anti-Fungal Activity against Candida auris of Cinnamomum cassia Essential Oil and of Its Nano-Formulations Based on Polycaprolactone

Candida auris represents an emerging pathogen that results in nosocomial infections and is considered a serious global health problem. The aim of this work was to evaluate the in vitro antifungal efficacy of Cinnamomum cassia essential oil (CC-EO) pure or formulated in polycaprolactone (PCL) nanoparticles against ten clinical strains of C. auris. nanoparticles of PCL were produced using CC-EO (nano-CC-EO) and cinnamaldehyde (CIN) through the nanoprecipitation method. The chemical profile of both CC-EO and nano-CC-EO was evaluated using SPME sampling followed by GC-MS analysis. Micro-broth dilution tests were performed to evaluate both fungistatic and fungicidal effectiveness of CC-EO and CIN, pure and nano-formulated. Furthermore, checkerboard tests to evaluate the synergistic action of CC-EO or nano-CC-EO with micafungin or fluconazole were conducted. Finally, the biofilm disrupting activity of both formulations was evaluated. GC-MS analysis shows a different composition between CC-EO and nano-CC-EO. Moreover, the microbiological analyses do not show any variation in antifungal effectiveness either towards the planktonic form (MICCC-EO = 0.01 ± 0.01 and MICnano-CC-EO = 0.02 ± 0.01) or the biofilm form. No synergistic activity with the antifungal drugs tested was found. both CC-EO and nano-CC-EO show the same antimicrobial effectiveness and are potential assets in the fight against C. auris.

Photoactive Oligomer with an Acceptor–Donor–Acceptor-Conjugated Structure for Single Near-Infrared Light-Triggered Photothermal/Photodynamic Synergistic Therapy of Tumors

Phototherapy is attracting increasing attention as a noninvasive, safe, and effective therapeutic modality for tumors. Especially, it is expected to achieve better therapeutic efficacy, fewer side effect, and deeper tissue penetration by the combination of photothermal (PTT) and photodynamic (PDT) under single near-infrared (NIR) light irradiation. For this purpose, herein, we develop a photoactive acceptor (A)–donor (D)–acceptor (A)-type conjugated oligomer (UF-TTOEH-2Cl). A NIR light-responsive nanoplatform (UTNPs) was fabricated based on UF-TTOEH-2Cl, and a folic acid-functionalized amphiphilic block copolymer (FA-PEG-PBLA10) was prepared as the polymer matrix through a nanoprecipitation method, which showed a high photothermal conversion efficiency (42%) and singlet oxygen (1O2) quantum yield (ΦΔ = 17.2%) under 880 nm laser irradiation. Furthermore, efficient UTNPs-based PDT/PTT synergistic therapy of tumors was demonstrated utilizing HeLa and SiHa cells as the models in vitro.

Incorporation of permethrin into chitosan polymeric nanoparticles using nanoprecipitation method for rubberwood preservation against termite attack

ABSTRACT Permethrin-loaded chitosan nanoparticle was successfully synthesised through the nanoprecipitation method. The hydrodynamic particle size and permethrin loading efficiency of the synthesised permethrin-chitosan nanoparticles were 199.7 ± 6.4 mm and 84.6 ± 2.20%, respectively. Hevea brasiliensis samples were then treated with 0.0025% w/v aqueous suspension of nanoparticles by vacuum pressure treatment. The optimisation studies proved that the pressure and duration of wood treatment with the permethrin-chitosan nanoparticles could be halved (100 psi and 60 min) as compared to the previously used standard condition (200 psi and 120 min). Results depict that the treatability and chemical retention achieved by the H. brasiliensis treated with permethrin-chitosan nanoparticles was 355.12 ± 9.50 L m−3 and 8.23 ± 1.23 kg m−3, respectively. Meanwhile, the weight loss of treated H. brasiliensis with permethrin-chitosan nanoparticles against subterranean termites; Coptotermes curvignathus reduced from 7.35 ± 0.080% to 1.20 ± 0.340%, whereas the visual rating increased from very severe attack to trace only (surface nibbles permitted). Findings from this study indicated that polymeric nanoparticles of chitosan could act as a carrier to deliver the permethrin into H. brasiliensis through water-based vacuum pressure treatment and also provide good protection against termites.

CENTRAL COMPOSITE FACE-CENTERED DESIGN-BASED OPTIMISATION, DEVELOPMENT AND CHARACTERISATION OF FAVIPIRAVIR-LOADED PLGA NANOPARTICLES

Objective: The objective of this study is to fabricate favipiravir-loaded PLGA nanoparticulate systems that can increase the solubility along with the sustained release of favipiravir. Methods: The favipiravir-loaded Poly (D, L-lactic-co-glycolide) (PLGA) nanoparticulate systems were prepared by the nanoprecipitation method. A 3-factor, 2-level central composite face-centered design was employed to study the effect of formulation variables having a concentration of PLGA, polyvinyl alcohol (PVA) and stirring rate as critical formulation attributes and particle size, drug entrapment efficiency, and percentage cumulative drug release as critical quality attributes on prepared favipiravir nanoparticles. Drug interaction studies were performed by FTIR and DSC. Surface morphology was analysed by scanning electron microscopy (FEI Quanta 250 FEG, USA). Particle size, zeta potential, and polydispersity index were analysed by the nanoparticle analyser SZ-100 (HORIBA Scientific nanopartica, Japan). In vitro drug release studies were performed using a UV-Visible spectrophotometer at λmax 234 nm. In vitro drug release data obtained was fitted into various mathematical kinetic models. Results: The numerical optimization process predicted the level of PLGA concentration as 69.96 mg, PVA concentration as 4.99%, and stirring rate as 799 rpm for the optimised formulation. The low percentage of relative error for the optimised formulation confirms the validation of the model. The optimised formulation had a 77.65% entrapment efficiency with a particle size of 109.7 nm and the percent cumulative drug release showed 86.46% drug release over 720 min. The drug release was found to follow first-order release kinetics with anomalous non-Fickian diffusion kinetics. Conclusion: Hence, such an attempt at fabrication of favipiravir-loaded PLGA nanoparticulate systems may be useful for sustained release of drug over 720 min.

A PHYSIOCHEMICAL STUDY ON DRUG DELIVERY OF METFORMIN HCL-LOADED CS-PLGA NANOPARTICLES

Objective: The current research was based on developing CS-PLGA nanoparticles (NPs) drug delivery system (DDS) for improving the bio-availability of metformin HCl, an anti-diabetic drug. Methods: Nanoprecipitation method was utilized to prepare the metformin HCl-loaded CS-PLGA NPs DDS. The metformin HCl-loaded NPs were validated using an analytical method and characterization of NPs was also done. These polymers release the drug in a controlled manner. Results: The correlation coefficient (R2) value for the metformin HCl calibration curve was 0.9971 in phosphate buffer pH 6.8 at a concentration range of 0-12 μg/ml. Metformin HCl-loaded NPs release the drug at 144 h, approximately 90%. DSC tests were carried out for 50 mg and 75 mg of MET HCl incorporated NPs and FT-IR for 50 mg of MET HCl incorporated NPs, it was clear from the FT-IR and DSC spectra that there were no interactions between the metformin HCl and the polymer. Conclusion: It was proven that metformin HCl-loaded NPs act as a prominent DDS by exhibiting extensive drug release and an increase in its bioavailability.

Copaiba Oil-Loaded Polymeric Nanocapsules: Production and In Vitro Biosafety Evaluation on Lung Cells as a Pre-Formulation Step to Produce Phytotherapeutic Medicine

Copaiba oil has been largely used due to its therapeutic properties. Nanocapsules were revealed to be a great nanosystem to carry natural oils due to their ability to improve the bioaccessibility and the bioavailability of lipophilic compounds. The aim of this study was to produce and characterize copaiba oil nanocapsules (CopNc) and to evaluate their hemocompatibility, cytotoxicity, and genotoxicity. Copaiba oil was chemically characterized by GC-MS and FTIR. CopNc was produced using the nanoprecipitation method. The physicochemical stability, toxicity, and biocompatibility of the systems, in vitro, were then evaluated. Β-bisabolene, cis-α-bergamotene, caryophyllene, and caryophyllene oxide were identified as the major copaiba oil components. CopNc showed a particle size of 215 ± 10 nm, a polydispersity index of 0.15 ± 0.01, and a zeta potential of -18 ± 1. These parameters remained unchanged over 30 days at 25 ± 2 °C. The encapsulation efficiency of CopNc was 54 ± 2%. CopNc neither induced hemolysis in erythrocytes, nor cytotoxic and genotoxic in lung cells at the range of concentrations from 50 to 200 μg·mL-1. In conclusion, CopNc showed suitable stability and physicochemical properties. Moreover, this formulation presented a remarkable safety profile on lung cells. These results may pave the way to further use CopNc for the development of phytotherapeutic medicine intended for pulmonary delivery of copaiba oil.

Antiangiogenic Potential of Troxerutin and Chitosan Loaded Troxerutin on Chorioallantoic Membrane Model.

Angiogenesis is crucial to the development of cancer because it allows the transport of oxygen, nutrients, and growth factors as well as the spread of tumors to distant organs. Inhibitors of angiogenesis prevent the formation of blood vessels that allow tumor cells to shrink, rather than promote tumor growth. Chitosan acts as a carrier for many drugs, since the compound has various properties such as biodegradable, less toxicity, more stable, simple, easy to prepare, and biocompatible. The aim of the current study was to evaluate the efficacy of chitosan nanoparticles encapsulated with troxerutin (Chi-Trox NPs) against angiogenesis and cancer in ova chick chorioallantoic membrane (CAM) model. Chi-Trox NPs were synthesized using a nanoprecipitation method and were characterized by various analyses. 24 hours' fertilized eggs (6 eggs/group) were treated with native Trox and Chi-Trox NPs for 5 days. The antiangiogenic activity was evaluated by morphometric, histopathological, immunohistochemical (CD104 and vimentin), and mRNA expression of MMP and FGF2 using RT-PCR. The anticancer activity was evaluated by histopathological, immunohistochmical (CD44), and mRNA expression of FGF2 and MMP. The synthesized chitosan NPs were successfully encapsulated with troxerutin, and the loading efficiency of chitosan NPs was found to be 86.4 ± 0.12% and 13.2 ± 0.16% respectively. Morphometric analysis of Chi-Trox NPs showed a considerable decrease in the number of blood vessels compared with control and native Trox. The histopathological observation of CAM confirmed that Chi-Trox NPs induce a significant reduction in inflammatory cells and the thickness of blood capillaries compared to control and native Trox. The immunohistochemical evaluation of CAM revealed Chi-Trox decreased CD104, vimentin and CD44 protein levels were compared with control and native Trox. Furthermore, the mRNA expression levels of FGF2 and MMP were significantly downregulated compared to their native forms. From the obtained results, Chi-Trox NPs possess significant inhibition of angiogenesis and can be used as therapeutic agents for cancer in the future.

Facile synthesis of poly(disulfide)s through one-step oxidation polymerization for redox-responsive drug delivery.

Poly(disulfide)s-based systems with repetitive disulfide bonds in their backbones are emerging as promising tumor microenvironment responsive platforms for drug delivery. However, complicated synthesis and purification processes have restricted their further application. Herein, we developed redox-responsive poly(disulfide)s (PBDBM) by one-step oxidation polymerization of a commercially available monomer, 1,4-butanediol bis(thioglycolate) (BDBM). PBDBM can self-assemble with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)3400 (DSPE-PEG3.4k) by the nanoprecipitation method and be formulated into PBDBM NPs (sub 100 nm). It can also be loaded with docetaxel (DTX), a first-line chemotherapy agent for breast cancer, to form DTX@PBDBM NPs with a loading capacity of 6.13%. DTX@PBDBM NPs with favorable size stability and redox-responsive capability exhibit superior antitumor activity in vitro. In addition, owing to the different glutathione (GSH) levels in normal and tumor cells, PBDBM NPs with disulfide bonds could synergistically increase intracellular ROS levels, further inducing apoptosis and cell cycle arrest in the G2/M phase. Moreover, in vivo studies revealed that PBDBM NPs could accumulate in tumors, suppress 4T1 tumor growth, and significantly attenuate the systemic toxicity of DTX. Thus, a novel redox-responsive poly(disulfide)s nanocarrier was successfully and facilely developed for cancer drug delivery and effective breast cancer therapy.

Nanoparticles Methods for Hydrophobic Drugs — A Novel Approach: Graphical Abstract

The current scenario shifts the advancement of technology toward nanotechnology as well as nanoparticles (NPs). Both are extensively used in pharmaceutical drug delivery also. NPs play a key role in the encapsulation of hydrophobic as well as hydrophilic drugs into the polymeric shells which leads to an increase in the solubility, absorption, encapsulation, and drug loading capacity of the drugs. The major limitations of hydrophobic drugs are solubility issues which hindered the drug’s bioavailability. These limitations can be overcome by polymeric NPs. Both subtypes of polymeric NPs, i.e., nanosphere and nanocapsules are also for the encapsulation of hydrophobic drugs. Our graphical review focused on hydrophobic drug encapsulation through polymeric NP formulation only via two methods, i.e., nanoprecipitation as well as solvent evaporation methods. Both methods are extensively used for hydrophobic drugs and also hold unique properties. The nanoprecipitation method is a single-step method based upon the nucleation process, whereas the solvent evaporation method is a two-step emulsification method. The present graphical review summarized the available remedies through NPs to increase the solubility of hydrophobic drugs.

Preparation and evaluation of cytotoxic potential of paclitaxel containing poly-3-hydroxybutyrate-co-3-hydroxyvalarate (PTX/PHBV) nanoparticles.

Paclitaxel (PTX) is a potent anticancer drug. In the present study, PTX was loaded in poly-3-hydroxybutyrate-co-3-hydroxyvalarate (PHBV) to fabricate the PTX/PHBV (drug-loaded) nanoparticles via the nanoprecipitation method. Blank PHBV nanoparticles were also prepared. The drug-encapsulation efficiency of PTX/PHBV nanoparticles was 45±0.4%. The PTX/PHBV nanoparticles exhibited a pH-sensitive release profile and followed a quasi-Fickian diffusion mechanism. Cytotoxic properties of PHBV and PTX/PHBV nanoparticles were checked against the MCF-7 and Caco-2 cell lines. The PHBV nanoparticle did not inhibit the proliferation of MCF-7 and Caco-2 cell lines, thus depicting their non-toxic and biocompatible nature. On the other hand, the PTX/PHBV nanoparticles demonstrated 1.03-fold higher cytotoxicity and 1.61-fold enhanced apoptosis after treatment with the PTX/PHBV nanoparticles versus free PTX. In summary, the PHBV nanoparticles could be a potential candidate for the delivery of PTX for cancer treatment.

Synergistic effects of radiotherapy with JNK inhibitor-incorporated nanoparticle in an intracranial Lewis Lung Carcinoma Mouse Models.

Radiosurgery has been recognized as a reasonable treatment for metastatic brain tumors. Increasing the radiosensitivity and synergistic effects are possible ways to improve the therapeutic efficacy of specific regions of tumors. c-Jun-N-terminal kinase (JNK) signaling regulates H2AX phosphorylation to repair radiation-induced DNA breakage. We previously showed that blocking JNK signaling influenced radiosensitivity in vitro and in an in vivo mouse tumor model. Drugs can be incorporated into nanoparticles to produce a slow-release effect. This study assessed JNK radiosensitivity following the slow release of the JNK inhibitor SP600125 from a poly (DL-lactide-co-glycolide) (LGEsese) block copolymer in a brain tumor model. A LGEsese block copolymer was synthesized to fabricate SP600125-incorporated nanoparticles by nanoprecipitation and dialysis methods. The chemical structure of the LGEsese block copolymer was confirmed by 1H nuclear magnetic resonance (NMR) spectroscopy. The physicochemical and morphological properties were observed by transmission electron microscopy (TEM) imaging and measured with particle size analyzer. The blood-brain barrier (BBB) permeability to the JNK inhibitor was estimated by BBBflammaTM 440-dye-labeled SP600125. The effects of the JNK inhibitor were investigated using SP600125-incorporated nanoparticles and by optical bioluminescence, magnetic resonance imaging (MRI), and a survival assay in a mouse brain tumor model for Lewis lung cancer (LLC)-Fluc cells. DNA damage was estimated by histone γH2AX expression and apoptosis was assessed by the immunohistochemical examination of cleaved caspase 3. The SP600125-incorporated nanoparticles of the LGEsese block copolymer were spherical and released SP600125 continuously for 24h. The use of BBBflammaTM 440-dye-labeled SP600125 demonstrated the ability of SP600125 to cross the BBB. The blockade of JNK signaling with SP600125-incorporated nanoparticles significantly delayed mouse brain tumor growth and prolonged mouse survival after radiotherapy. γH2AX, which mediates DNA repair protein, was reduced and the apoptotic protein cleaved-caspase 3 was increased by the combination of radiation and SP600125-incorporated nanoparticles.

Influence of organic to aqueous phase solvent volume ratio on the physicochemical characteristics of rosuvastatin and ezetimibe loaded lipid-polymer hybrid nanoparticles prepared by nanoprecipitation method

Influence of organic to aqueous phase solvent volume ratio on the physicochemical characteristics of rosuvastatin and ezetimibe loaded lipid-polymer hybrid nanoparticles prepared by nanoprecipitation method

Combination of Quercetin or/and siRNA-loaded DDAB-mPEG-PCL hybrid nanoparticles reverse resistance to Regorafenib in colon cancer cells

BackgroundColorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5β1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro.MethodsRegorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the β1 subunit of integrin were determined by the real-time method of RT-PCR.ResultsDeveloped Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The β1 mRNA level of whole α5β1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy.ConclusionResults of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro.

Doxorubicin Hydrochloride-loaded Nanoparticles for Oral Delivery: Optimization using Design of Experiments

Doxorubicin hydrochloride (DOX) has low oral bioavailability due to the presence of active efflux from intestinal P-glycoprotein receptors. Because of the difficulties associated with the oral administration of DOX, there is not yet a commercially available oral formulation of DOX. Nanocarrier system was manufactured utilizing poly (lactic-co-glycolic acid) (PLGA) and treated with chitosan to provide a surface coated. Nanoparticles (NPs) were created using a modified emulsification solvent diffusion (nanoprecipitation) method by electrostatic conjugation of chitosan to modify nanoparticle surfaces. The model was built using a Box-Behnken design with three independent components: X1 (PLGA), X2 (poloxamer 188), and X3 (chitosan concentration). The optimized chitosan-PLGA NPs had a mean particle size of 153.6 nm and a positive zeta potential of 21.51 mV. More than 85% DOX permeated through the everted gut by DOX-loaded chitosan-NPs as compared to NPs prepared with PLGA alone. Chitosan nanoparticles caused a 6-fold increase in DOX intestinal permeability. The findings pointed to the possibility of using chitosan-based nanoparticles of doxorubicin for oral treatment for cancer.

Synthesis of Carrier-Free Paclitaxel-Curcumin Nanoparticles: The Role of Curcuminoids.

The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor water solubility. Herein, we synthesized carrier-free PTX NPs by a facile nanoprecipitation method with the help of CUR and other curcuminoids present in turmeric extract. The prepared NPs demonstrated spherical morphologies with high conformational stability. Experimental studies showed that the presence of both bisdemethoxycurcumin and demethoxycurcumin is essential for the successful formation of spherical and monodisperse NPs. Computational studies revealed that the presence of the more sterically available curcuminoids BMC and DMC makes the self-assembly procedure more adaptable with a higher number of potential conformations that could give rise to more monodisperse PTX-CUR NPs. Compared with PTX alone, PTX-CUR NPs have shown comparable therapeutic efficiency in vitro and demonstrated a higher cellular internalization, highlighting their potential for in vivo applications. The successful formation of PTX-CUR NPs and the understanding of how multiple drugs behave at the molecular level also provide guidance for developing formulations for the synthesis of high-quality and effective carrier-free nanosystems for biomedical applications.

Self-Assembled Lipid Polymer Hybrid Nanoparticles Using Combinational Drugs for Migraine Via Intranasal Route

The objective of the current research study was to formulate the PEGylated lipid polymer hybrid nanoparticles of ergotamine and caffeine for intranasal administration with higher entrapment efficiency, better permeability, desirable controlled release pattern, and significant brain uptake in animal studies. A single-step nanoprecipitation method was employed in the processing of self-assembled hybrid nanoparticles constituting polymer PLGA, lipids soya lecithin, and DPPC with PEGylation using polyethylene glycol (PEG-2000). The optimal lipid/polymer weight ratio of 15% w/w showed lower particle size of 239.46 ± 2.31nm with good colloidal stability depicted by zeta potential (- 18.36 ± 6.59mV), higher entrapment efficiency of 86.88 ± 1.67%, and controlled release profile when evaluated for in vitro and ex vivo studies as 97.12 ± 2.79% and 75.13 ± 5.62% release, respectively, for 48h. The formulation showed long-term serum stability when incubated in bovine serum albumin and displayed high brain uptake (4.35-fold) offering significant permeability in the brain post-intranasal administration via olfactory route. Histopathological investigations and serotonin toxicity studies in animals confirmed the safe and non-toxic nature of the formulation while the acetic acid writhing test proved the anti-hyperalgesic activity. The PEGylated lipid polymer hybrid nanoparticles of ergotamine and caffeine showed synergistic activity with efficacious higher anti-migraine potential.

A novel ROS-activable self-immolative prodrug for tumor-specific amplification of oxidative stress and enhancing chemotherapy of mitoxantrone

Reactive oxygen species (ROS) as well-known endogenous stimuli has been widely used to activate drug delivery systems (DDSs) for tumor-specific therapy. Unfortunately, endogenous ROS in the tumor microenvironment (TME) is not enough to achieve effective therapeutic efficacy and cancer cells have adapted to high oxidative stress by upregulating glutathione (GSH) level. Herein, we devised a novel ROS-activable self-immolative prodrug CASDB with both GSH-depletion ability and ROS self-supply competence. Then, an stimuli-responsive nanoplatform integrating CASDB with clinical chemotherapeutics mitoxantrone (MTO) and PLGA was fabricated (denoted as CMPs) through nanoprecipitation method. The CMPs could achieve desired accumulation at tumor tissues through enhanced permeability and retention (EPR) effects. Then the accumulated CMPs could induce tumor cell apoptosis efficiently. Especially, ROS in tumor sites could trigger the immolation of CASDB to generate CA and quinone methide (QM). Then CA and QM cooperatively promoted damage of mitochondria due to oxidative stress and led to cancer cells more sensitive to MTO. Accordingly, MTO could perturb cellular microenvironment of cancer cells then promote the degradation of CASDB. The experiment results demonstrated that CMPs were ideal for desirable synergetic tumor-specific anticancer therapy with negligible systemic toxicity. The half-maximal inhibitory concentrations (IC50) value of CMPs was 6.53 μM, while the IC50 values of MTO was 14.76 μM. And the CMPs group showed the strongest tumor suppressor effect with the tumor sizes increased to 1.2-fold (Control group: 20.6-fold, MTO only: 3.0-fold). This study should be inspirational for designing efficient prodrugs to overcome the handicaps of traditional chemotherapy.

Recyclable Biomass-Derived Polyethylene-Like Materials as Functional Coatings for Commercial Fabrics: Toward Upcycling of Waste Textiles

Bio-based polymers are recognized as promising alternatives to fossil-based counterparts. However, the inferior material performance of bio-based polymers is a serious restriction to their application fields. Herein, renewable polyethylene-like materials (PLMs) are used as surface coatings for commercial fabrics. First, α,ω-diene monomers were synthesized by the downstream products of sugar and castor oil derivatives. Subsequently, biomass-derived polymers were generated via acyclic diene metathesis (ADMET) (co)polymerization of these monomers followed by exhaustive hydrogenation. The obtained long-chain aliphatic polyesters are considered remarkable polyethylene mimics in that these hydrophobic and semicrystalline materials show unique features such as hydrolysis resistance and recyclability. On the other hand, PLM nanoparticles were prepared by the nanoprecipitation method and then drop-cast on commercial fabric surfaces. Hydrophobically modified fabrics show repellency to various water droplets and the capability of oil/water separation as well as anti-icing and anticorrosive characteristics. Moreover, photoinduced contaminant removal and wettability change are realized by fabrics with a hybrid coating layer composed of PLM and titanium dioxide (TiO2) nanoparticles. These polyethylene-mimetic materials not only meet the requirements of sustainability in terms of renewability and recyclability but also show great prospects in surface functionalization of commercial fabrics and upcycling of waste textiles.

Preparation of Wide-Domain pH Color-Changing Nanocapsules and Application in Hydrogel Fibers.

In recent years, there has been an increase in demand for pH color-changing materials. These materials can visually communicate signals to people by connecting pH changes with color information. Embedding pH indicators into fibers to create flexible color-changing materials is an effective way to develop daily wearable products. For the stability of the indicator and the indirect contact of the indicator with the human body, it is usually necessary to encapsulate it in capsules. In this study, different pH indicators (Thymol Blue-TB, Bromocresol Green-BCG, and Bromocresol Purple-BCP) were mixed into a wide-domain pH color-changing indicator and encapsulated with ethyl cellulose (EC) by the flash nanoprecipitation (FNP) method using a new-type droplet-shaped confined impinging jet mixer. The effects of flow rate, core-to-wall ratio, and mixed solution concentration on the formation of the nanocapsules were investigated. In addition, the morphology, particle size, size distribution, dispersion stability, and encapsulation efficiency were systematically studied. At a core-to-wall ratio of 1:2, a mixed solution with a concentration of 6 mg/mL and a feed flow rate of 40 mL/min produced nanocapsules with an average particle size of 141.83 ± 0.98 nm and a PDI of 0.125 ± 0.01. Furthermore, a zeta potential with a range of -31.83 ± 0.23 mV and an encapsulation efficiency of 75.20 ± 1.72% were observed at 1:2 core-to-wall ratios. It was concluded that the color of the nanocapsules continuously changed from yellow to green and green to blue when the pH range was increased from 3 to 10. The color-changing nanocapsules were then embedded into sodium alginate hydrogel fibers, resulting in the same color-changing trend (pH 3-10) as that obtained for the nanocapsules. This study can be useful for the pH monitoring of various body fluids, such as wound exudate, urine, and sweat.