Tocopheryl Polyethylene Glycol Succinate Research Articles

Preparation, Optimization and In Vitro Characterization of Fluticasoneloaded Mixed Micelles Based on Stearic Acid-g-chitosan as a Pulmonary Delivery System.

The primary objective of this study was to optimize formulation variables and investigate the in vitro characteristics of fluticasone propionate (FP)-loaded mixed polymeric micelles, which were composed of depolymerized chitosan-stearic acid copolymer (DC-SA) in combination with either tocopheryl polyethylene glycol succinate or dipalmitoylphosphatidylcholine for pulmonary drug delivery. A D-optimal design was employed for the optimization procedure, considering lipid/ polymer ratio, polymer concentration, drug/ polymer ratio, and lipid type as independent variables. Dependent variables included particle size, polydispersion index, zeta potential, drug encapsulation efficiency, and loading efficiency of the polymeric micelles. Additionally, the nebulization efficacy and cell viability of the optimal FP-loaded DC-SA micellar formulations were evaluated. The mixed polymeric micelles were successfully prepared with properties falling within the desired ranges, resulting in four optimized formulations. The release of FP from the optimal systems exhibited a sustained release profile over 72 hours, with 70% of the drug still retained within the core of the micelles. The nebulization efficiency of these optimal formulations reached up to 63%, and the fine particle fraction (FPF) ranged from 41% to 48%. Cellular viability assays demonstrated that FP-loaded DC-SA polymeric micelles exhibited lower cytotoxicity than the free drug but were slightly more cytotoxic than empty mixed micelles. In conclusion, this study suggests that DC-SA/ lipid mixed micelles have the potential to serve as effective carriers for nebulizing poorly soluble FP.

An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line

Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the effects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efficiency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and flow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of − 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC50) values for FA from O2 and free FA were calculated against different cell lines showing a prominent IC50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 significantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P < 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer effect of FA against colorectal cancer, probably due to its enhanced solubility. Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy.

Chitosan film of thiolated TPGS-modified Au-Ag nanoparticles for combating multidrug-resistant bacteria

The widely used vitamin-E based amphiphilic material, tocopheryl polyethylene glycol succinate (TPGS) was further improvised to redox-sensitive thiolated TPGS (TPGS-SH), which has been achieved by attaching 4-aminothiophenol. Further, TPGS and TPGS-SH-coated bimetallic gold-silver nanoparticles (TPGS-Au-Ag-NP and TPGS-SH-Au-Ag-NP) were formulated to explore their antibacterial and wound healing abilities. The prepared NP were monodisperse with a mean hydrodynamic diameter of 69.5±3.23 nm, 59.65±3.23 nm, PDI of 0.3±0.05, 0.2±0.03 and a zeta potential of +29.2±2.71 mV and +35.28±1.53 mV, respectively. The TPGS and TPGS-SH modified Au-Ag-NP were tested for their antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli; minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) results showed that TPGS Au-Ag-NP, TPGS-SH-Au-Ag-NP displayed significantly stronger antibacterial activity than their coating material alone. The anti-efflux pump activity of the most potent antibacterial agent TPGS-SH-Au-Ag-NP was evaluated against MRSA. Toxicity assessment of TPGS-SH-Au-Ag-NP in human dermal fibroblasts showed 88% viability up to 125 µg/mL. The TPGS-SH-Au-Ag-NP, after incorporation in chitosan film (TPGS-SH-Au-Ag-NP-CS), exhibited sustained release and prolonged in vivo residence characteristics, which were evaluated by IVIS. Results also revealed that treatment with TPGS-SH-Au-Ag-NP showed a significant 87% wound healing rate after 12 days of application in the rat model. Hence, we concluded that TPGS-SH-Au-Ag-NP was safe and effective against test bacteria MRSA and capable of efficient wound healing when incorporated in chitosan film.

Surface Modified Carvacrol-rich Satureja khuzestanica Essential Oil Nanoemulsion: A Novel Paclitaxel Formulation Induced Apoptosis on Paclitaxel-Resistant Breast Cancer Cells

Background: The ability of cancer cells to develop multidrug resistance (MDR) is a major challenge in modern chemotherapy. The current generation of commercially available paclitaxel formulations have not been designed to treat resistant tumours. In this study, a nanoemulsion-based delivery system was developed to enhance the efficacy of paclitaxel against resistant breast cancer cells. Methods: The nanoemulsion was formulated using carvacrol-rich Satureja khuzestanica essential oil. Modification of nanoemulsion was performed by incorporating tocopheryl polyethylene glycol 1000 succinate (TPGS) which could inhibit drug resistance in cancer cells. Fabrication of paclitaxel nanoemulsion was performed by high speed homogenization. The cytotoxicity of prepared formulation against resistant breast cancer cells was investigated by MTT assay. Flow cytometry technique was used for cell cycle arrest analysis and examination of the apoptosis induction ability of prepared nanoemulsion. Results: The nanoemulsion had a relatively small mean droplet diameter (93.6 ± 4.2 nm) and good long-term stability. The ability of paclitaxel to inhibit P-gp function in paclitaxel-resistant breast cancer cells (MCF-7/PTX) was synergistically enhanced by administering it within the nanoemulsion. The cytotoxicity of the prepared nanoemulsion on the HUVEC normal cells was much lower than that of MCF-7/PTX cells. Cell cycle analysis utilizing flow cytometry showed that the paclitaxel-loaded nanoemulsion promoted G2-M arrest. Flow cytometry also demonstrated that this nanoemulsion induced apoptosis in MCF-7/PTX cells. Interestingly, apoptosis increased from 20.0% for the free paclitaxel treated group to 85.2 % for the paclitaxel-loaded nanoemulsion treated group. Conclusion: This novel paclitaxel nanoemulsion efficiently suppressed the drug resistance of breast cancer cells and induced effective apoptosis in very low concentrations of paclitaxel.

DEVELOPMENT OF ERLOTINIB ENCAPSULATED SELF-ASSEMBLED MIXED MICELLES: OPTIMIZATION AND IN VITRO EVALUATION

For the treatment of lung cancer, erlotinib is used as primary treatment. Erlotinib is an epidermal growth factor receptor inhibitor, however it is deposited in normal cells also and clinicians do not prefer it. This constraint opens the way for development of targeted therapy. Mixed micelles via self-assembly have the functionality to improve the delivery of hydrophobic drugs, and improve the pharmacokinetics of the loaded drug. Pluronic® F127 and tocopheryl polyethylene glycol succinate were used to prepare micelles. BoxBehnken design was applied to optimize formulation. With optimum ratio, micelles were characterized, and pharmacokinetic parameters were predicted. Design batches F1 to F15, showed the range of 42-133 nm size and 55-82 % of entrapment. Critical micelles concentration was found to be 3 × 10-5 M. Drug release of optimized mixed micelles was found 84.91± 1.58 % in 72 h. In a nutshell, self-assembled mixed micelles would be a suitable delivery platform for targeting anticancer agents.

EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel: Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging.

In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 μg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.

Vitamin E modified polyamidoamine dendrimer for piperine delivery to alleviate Aβ1–42 induced neurotoxicity in Balb/c mice model

In Alzheimer’s disease (AD), amyloid beta (Aβ1-42) aggregate formation and neurofibrillary tangles are major pathological hallmarks which are related to neurodegeneration in the brain. To alleviate Aβ1-42 fibrils toxicity vitamin E derivative tocopheryl polyethylene glycol succinate (TPGS) was conjugated with polyamidoamine (PAMAM) dendrimer through carbodiimide reaction to synthesize TPGS-PAMAM. This TPGS-PAMAM was employed to entrap neuroprotective agent piperine (PIP) through an anti-solvent technique to prepare PIP-TPGS-PAMAM. The dendrimer conjugate was prepared to reduce Aβ1-42 induced neurotoxicity and increase acetylcholine levels in AD mice models. The synthesis of dendrimer conjugate was characterized through proton nuclear magnetic resonance (NMR) and Trinitrobenzene sulphonic acid assay (TNBS). Physical characterization of dendrimers conjugates were done through various spectroscopic, thermal and microscopy based techniques. PIP-TPGS-PAMAM showed 43.25 nm particle size with PIP percentage encapsulation efficiency of 80.35%. Further Aβ1-42 fibril disaggregation effect of nanocarrier was evaluated using Thioflavin–T (ThT) assay and circular dichroism (CD). The neuroprotection studies for PIP-TPGS-PAMAM was evaluated against neurotoxicity induced using Aβ1–42 intracerebroventricular (ICV) injected in Balb/c mice. The group of mice administered with PIP-TPGS-PAMAM exhibited an increase in the proportion of random alternations in T-maze test and novel object recognition test (NORT) exhibited an increase in working memory cognitive functions. The biochemical and histopathological analysis revealed PIP-TPGS-PAMAM treated groups enhanced acetylcholine levels, reduced ROS and Aβ1-42 content significantly. Our findings imply that PIP-TPGS-PAMAM enhanced memory and reduced cognitive deficit in mice brain induced by Aβ1-42 toxicity.

β-catenin inhibition using XAV939 nanoparticle promotes immunogenic cell death and suppresses tumor progression

Abstract Although the incidence of conjunctival melanoma is rare, it is a highly metastatic tumor with high recurrence and mortality rates. The current conjunctival melanoma treatment strategies, including surgical resection combined with chemo- or cryotherapy, have limited usefulness because of systemic side effects, recurrence, and metastases. Tumor-intrinsic Wnt/β-catenin pathway mediates immune exclusion in the tumor microenvironment (TME) and promotes tumorigenesis. Previous studies have shown that XAV939, a potent tankyrase inhibitor, can be used for the pharmacological inhibition of β-catenin. In this study, using tocopheryl polyethylene glycol 1000 succinate (TPGS)-based nanoparticle formulation for XAV939, we show that β-catenin inhibition suppresses melanoma cell proliferation and migration. Additionally, XAV939 nanoparticles promoted immunogenic cell death (ICD) of tumor cells with a significant extracellular release of ICD molecules, including HMGB1, calreticulin, and ATP. Further, using a mouse model of conjunctival melanoma, we show that β-catenin inhibition significantly suppresses conjunctival melanoma progression. Collectively, the local delivery of β-catenin represents a novel and safe approach to promoting ICD and activating anti-tumor immunity for combinatorial immune checkpoint inhibition therapies against vision and life-threatening ocular melanomas. This study was supported by research funding from the Intramural Grants Program, Auburn University Research Initiative in Cancer (AURIC), and start-up funds from the Department of Pathobiology, College of Veterinary Medicine, Auburn University.

Formulation and evaluation of a two-stage targeted liposome coated with hyaluronic acid for improving lung cancer chemotherapy and overcoming multidrug resistance

Multidrug resistance (MDR) has emerged as a prominent challenge contributing to the ineffectiveness of chemotherapy in treating non-small cell lung cancer (NSCLC) patients. Currently, mitochondria of cancer cells are identified as a promising target for overcoming MDR due to their crucial role in intrinsic apoptosis pathway and energy supply centers. Here, a two-stage targeted liposome (HA/TT LP/PTX) was successfully developed via a two-step process: PTX-loaded cationic liposome (TT LP/PTX) were formulated by lipid film hydration & ultrasound technique, followed by further coating with natural anionic polysaccharide hyaluronic acid (HA). TT, an amphipathic polymer conjugate of triphenylphosphine (TPP)-tocopheryl polyethylene glycol succinate (TPGS), was used to modify the liposomes for mitochondrial targeting. The average particle size, zeta potential and encapsulation efficiency (EE%) of HA/TT LP/PTX were found to be 153 nm, −30.3 mV and 92.1% based on the optimal prescription of HA/TT LP/PTX. Compared to cationic liposome, HA-coated liposomes showed improved stability and safety, including biological stability in serum, cytocompatibility, and lower hemolysis percentage. In drug-resistant A549/T cells, HA was shown to improve the cellular uptake of PTX through CD44 receptor-mediated endocytosis and subsequent degradation by hyaluronidase (HAase) in endosomes. Following this, the exposure of TT polymer facilitated the accumulation of PTX within the mitochondria. As a result, the function of mitochondria in A549/T cells was disturbed, leading to an increased ROS level, decreased ATP level, dissipated MMP, and increased G2/M phase arrest. This resulted in a higher apoptotic rate and stronger anticancer efficacy.

Hyaluronan-based theranostic nanomicelles for breast cancer-targeting and anticancer drug delivery

Integration of diagnostic and therapeutic modalities into a single nanoplatform can play an important role in personalized cancer therapy. In this work, an all-in-one theranostic nanoplatform (HPCT nanomicelles) for breast cancer was fabricated, composed of the synthetic polymer hyaluronan-b-poly(ε-caprolactone) (HA-PCL), drug curcumin (Cur) and adjuvant tocopheryl polyethylene glycol succinate (TPGS). HPCT nanomicelles presented adequate drug loading efficiency, excellent stability, and attractive hyaluronidase-sensitive release features. Imaging agent radionuclide 99mTc was loaded into HPCT nanomicelles (denoted as 99mTc-HPCT nanomicelles) and in vivo SPECT/CT imaging verified the HA-based nanomicelles could actively target breast cancer in mice. In vivo anti-tumor pharmacodynamic studies indicated that HPCT nanomicelles exhibited desirable anti-tumor efficacy with favorable biosafety. 99mTc-HPCT nanomicelles, integrating imaging and therapeutic modalities, have the promising potential to be an all-in-one theranostic nanoplatform for breast cancer.

Redox homeostasis modulation using theranostic AIE nanoparticles results in positive-feedback drug accumulation and enhanced drug penetration to combat drug-resistant cancer.

Drug-resistant cancers usually have multiple barriers to compromise the effect of therapies, of which multidrug-resistance (MDR) phenotype as the intracellular barrier and dense tumor matrix as the extracellular barrier, significantly contribute to the poor anticancer performance of current drug delivery systems (DDS). Here in this study, we fabricated a novel aggregation-induced emission (AIE)-active polymer capable of self-assembling into ultrasmall nanoparticles (∼20 ​nm) with D-alpha Tocopheryl Polyethylene Glycol Succinate (TPGS), for dual-encapsulating of doxorubicin (Dox) and sulforaphane (SFN) (AT/Dox/SFN). It revealed that redox homeostasis modulation of MDR cells (MCF-7/Adr) using AT/Dox/SFN can trigger mitochondria damage and ATP deficiency, which reverse the MDR phenotype of MCF-7/Adr cells to afford enhanced cellular uptake of both drug and DDS in a positive-feedback manner. The enhanced cellular drug accumulation further initiates the “neighboring effect” for improved drug penetration. Using this strategy, the growth of in vivo MCF-7/Adr tumors can be effectively inhibited at a low dosage (1/5) of doxorubicin (Dox) as compared to free Dox. In summary, we offer a new approach to overcome both the intracellular and extracellular barriers of drug-resistant cancers and elucidate the potential action mechanisms, which are beneficial for better cancer management.

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia

Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae. After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae. After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.

Comparative Evaluation of Antimicrobial, Antiamoebic, and Antiviral Efficacy of Ophthalmic Formulations.

The extensive use of ophthalmic antibiotics is contributing to the appearance of resistant bacterial strains, which require prolonged and massive treatments with consequent detrimental outcomes and adverse effects. In addition to these issues, antibiotics are not effective against parasites and viruses. In this context, antiseptics could be valuable alternatives. They have nonselective mechanisms of action preventing bacterial resistance and a broad spectrum of action and are also effective against parasites and viruses. Here, we compare the in vitro antibacterial, antiameobic, and antiviral activities of six ophthalmic formulations containing antiseptics such as povidone-iodine, chlorhexidine, and thymol against Gram-positive and Gram-negative bacteria, the amoeba Acanthamoeba castellanii, and two respiratory viruses, HAdV-2 and HCoV-OC43. The results suggest that, among all the tested formulations, Dropsept, consisting of Vitamin E TPGS-based (tocopheryl polyethylene glycol succinate) in combination with the antiseptic chlorhexidine, is the one with the highest range of activities, as it works efficiently against bacteria, amoeba, and viruses. On the other hand, the solution containing PVA (polyvinyl alcohol) and thymol showed a promising inhibitory effect on Pseudomonas aeruginosa, which causes severe keratitis. Given its high efficiency, Dropsept might represent a valuable alternative to the widely used antibiotics for the treatment of ocular infections. In addition to this commercial eye drop solution, thymol-based solutions might be enrolled for their natural antimicrobial and antiamoebic effect.

Promoted cellular uptake and intracellular cargo release of ICG/DOX-carrying hybrid polymeric nanoassemblies upon acidity-activated PEG detachment to enhance cancer photothermal/chemo combination therapy

Some studies have reported that the PEGylation of nanoparticle-based drug delivery systems could increase drug solubility, prolong systematic circulation time of drug carriers and decrease immunogenicity. Nevertheless, the uptake of these PEGylated nanoparticles by cancer cells was largely hindered. To promote intracellular co-delivery of indocyanine green (ICG), an amphiphilic photothermal transduction agent, and doxorubicin (DOX), a chemotherapy drug, for improved anticancer efficacy of the photothermal/chemo combination therapy, the hybrid polymeric nanoassemblies equipped with acid-activated PEG detachment were developed as vehicles by co-assembly of hydrophobic poly(lactic-co-glycolic acid) (PLGA), pH-responsive methoxy poly(ethylene glycol)-benzoic imine-octadecane (mPEG5k-b-C18) and amphiphilic tocopheryl polyethylene glycol succinate (TPGS) segments in aqueous solution of pH 8.0. The ICG/DOX-carrying mPEG5k-b-C18/TPGS/PLGA nanoassemblies (ID@PbCTPNs) were characterized to exhibit a well-dispersed spherical shape and maintained stable colloidal structure in serum-containing solution. Also ID@PbCTPNs sufficiently reduced ICG self-aggregation and leakage in pH 7.4 aqueous solution, thereby enhancing aqueous photostability and photo-elicited hyperthermia of ICG molecules. With the solution pH being lowered from 7.4 to 5.0, the acid-triggered dePEGylation of ID@PbCTPNs not only led to reduction of particle size but also accelerated cargo liberation. The findings of in vitro cellular uptake and cytotoxicity revealed that the cellular uptake and intracellular drug release of ID@PbCTPNs was appreciably increased via acid-elicited dePEGylation, thus largely promoting their anticancer potency on TRAMP-C1 cells by the photothermal/chemo combinatorial therapy. This work demonstrates that the designed ID@PbCTPNs show the promising application in cancer treatment.

Dual Loading of Doxorubicin and Magnetic Iron Oxide into PLA-TPGS Nanoparticles: Design, in vitro Drug Release Kinetics, and Biological Effects on Cancer Cells.

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer co-loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA-TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.

A selective and inert stationary phase combining triptycene with tocopheryl polyethylene glycol succinate for capillary gas chromatography

This work reports a selective and inert triptycene-based stationary phase (TPT) combining the triptycene framework with tocopheryl polyethylene glycol succinate (TPGS) units for capillary gas chromatography (GC). The TPT stationary phase was physically coated onto a capillary column by static coating method with the column efficiency of 4200 plates/m and moderate polarity. As demonstrated, the TPT column exhibited high inertness towards organic bases, including basic heterocycles, aliphatic and aromatic amines, showing distinct advantages over the TPGS and commercial columns. Also, the TPT column displayed high-resolution performance towards the isomers of methylpyridines, toluidines, xylidines and alkanes (C6–C8). Moreover, it showed excellent separation repeatability and reproducibility with RSD values in the range of 0.03%-0.07% for run-to-run, 0.12%–0.18% for day-to-day and 2.3%–3.6% for column-to- column (n = 4). Its applications to purity test of chemical products and to GC-MS analysis of the essential oil of Artemisia annua L. demonstrated its good potential for practical analyses. The present work has novelty in constructing highly selective and inert stationary phases and providing a feasible strategy for concurrently addressing the related problems in GC analyses. Its methodology and findings is of important value in terms of fundamental researches and practical applications.

Poly (Lactic-co-Glycolic Acid) & Tocopheryl Polyethylene Glycol Succinate Nanoparticles for the Treatment of Different Brain Cancers.

Nanotechnology and material science developments emerge in the manufacturing of various novel modes of drug delivery, which have proven scientifically promising. Polymer nanoparticles have high stability, high specificity, high drug-carrying power, control release, and potential to be used in various pathways. They usually supply hydrophilic and hydrophobic molecules with medicines. In this review, we have discussed the different types of brain tumour, different PLGA (Poly Lactic-co-Glycolic Acid) nanostructures, PLGA in brain tumour targeting, and the recent advancement of PLGA based nanoparticles. This review focused on the method of preparation of polymeric nanoparticles, the significance of EPR (Enhanced Permeability and Retention) effect with PLGA, the significance of TPGS in cancer, and discussed the pharmaceutical application of PLGA nanoparticles. We expect these polymeric nanoparticles will be very successful and efficient for disease targeting in the future and new techniques will emerge.

Indocyanine green-carrying polymeric nanoparticles with acid-triggered detachable PEG coating and drug release for boosting cancer photothermal therapy

In order to boost anticancer efficacy of indocyanine green (ICG)-mediated photothermal therapy (PTT) by promoting intracellular ICG delivery, the ICG-carrying hybrid polymeric nanoparticles were fabricated in this study by co-assembly of hydrophobic poly(lactic-co-glycolic acid) (PLGA) segments, ICG molecules, amphiphilic tocopheryl polyethylene glycol succinate (TPGS) and pH-responsive methoxy poly(ethylene glycol)-benzoic imine-1-octadecanamine (mPEG-b-C18) segments in aqueous solution. The ICG-loaded nanoparticles were characterized to have ICG-containing PLGA core stabilized by hydrophilic PEG-rich surface coating and a well-dispersed spherical shape. Moreover, the ICG-loaded nanoparticles in pH 7.4 aqueous solution sufficiently inhibited ICG self-aggregation and leakage, thereby increasing aqueous photostability of ICG molecules. Notably, when the solution pH was reduced from pH 7.4–5.5, the acid-triggered hydrolysis of benzoic-imine linkers within mPEG-b-C18 remarkably facilitated the detachment of mPEG segments from ICG-loaded nanoparticles, thus accelerating ICG release. The findings of in vitro cellular uptake and cytotoxicity studies further demonstrated that the PEGylated ICG-carrying hybrid nanoparticles were efficiently internalized by MCF-7 cells compared to free ICG and realized intracellular acid-triggered rapid ICG liberation, thus enhancing anticancer effect of ICG-mediated PTT to potently kill cancer cells.

Amphiphilic tocopheryl polyethylene glycol succinate as gas chromatographic stationary phase for high-resolution separations of challenging isomers and analysis of lavender essential oil.

This work presents the investigation of using tocopheryl polyethylene glycol succinate as the stationary phase for gas chromatography separations of isomers with different varieties and gas chromatography-mass spectrometry analysis of a wide range of components in lavender essential oil. Its capillary column exhibited moderate polarity and column efficiency of 4000 plates/m determined by n-dodecane at 120°C. As demonstrated, it showed outstanding separation performance toward challenging isomers such as xylenes, alkanes, phenols, and anilines and a wide range of components in essential oils with distinct advantages over the commercial polyethylene glycol and polysiloxane columns. Moreover, its capillary columns displayed excellent repeatability and reproducibility with the RSD values of the retention times in the range of 0.02-0.07% for run-to-run, 0.14-0.22% for day-to-day, and 2.5-4.3% for column-to-column. Its application to gas chromatography-mass spectrometry analysis of the lavender essential oil proved its good potential for practical gas chromatography analyses. To our knowledge, this work presents the first example of employing tocopheryl polyethylene glycol succinate for chromatographic analyses and demonstrates its promising future in this field.

Drug crystal growth in ternary amorphous solid dispersions: Effect of surfactants and polymeric matrix-carriers

The present study evaluates the crystal growth rate of amorphous drugs when dispersed in different ternary polymeric amorphous solid dispersions (ASDs) in the presence of surfactants. Specifically, ternary ASDs of aprepitant (APT, selected as a model drug) were prepared via melt-quench cooling by evaluating three commonly used ASDs matrix/carriers, namely hydroxypropyl cellulose (HPC), poly(vinylpyrrolidone) (PVP) and the copolymer Soluplus® (SOL), and two suitable surfactants, namely d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P407). Results showed that all components were completely miscible (verified via hot stage polarized microscopy) and both surfactants were acting as plasticizers to the API. APT's crystal growth rate was increased in the presence of both P407 and TPGS, while PVP was identified as the matrix/carrier with the greatest impact API's crystal growth rate inhibition. Interestingly, TPGS presented a noticeable synergistic effect when combined with PVP resulting in a further reduction of APT's crystal growth rate. Furthermore, evaluation of APT's nucleation induction time in dissolution medium (PBS pH 6.8) revealed PVP as the most effective crystallization inhibitor, whereas the addition of TPGS showed to improve PVP's ability to inhibit APT's recrystallization. Finally, the formation of intermolecular interactions in the ternary APT-PVP-TPGS provided an explanation for the observed PVP-TPGS synergistic effects, with molecular dynamics simulations being able to unravel the type and extent of these interactions on a theoretical basis.