Vitamin E-TPGS Research Articles

Preparation of biocompatible Zein/Gelatin/Chitosan/PVA based nanofibers loaded with vitamin E-TPGS via dual-opposite electrospinning method

Wound management is a critical aspect of healthcare, necessitating effective and innovative wound dressing materials. Many existing wound dressings lack effectiveness and exhibit limitations, including poor antimicrobial activity, toxicity, inadequate moisture regulation, and weak mechanical performance. The aim of this study is to develop a natural-based nanofibrous structure that possesses desirable characteristics for use as a wound dressing. The chemical analysis confirmed the successful creation of Zein (Ze) (25% w/v) /gelatin (Gel) (10% w/v) /chitosan (CS) (2% w/v) /Polyvinyl alcohol (PVA) (10% w/v) nanofibrous scaffolds loaded with vitamin E tocopheryl polyethylene glycol succinate (Vit E). The swelling percentages of nanofiber (NF), NF + Vit E, cross-linked nanofiber (CNF), and CNF + Vit E were 49%, 110%, 410%, and 676%, respectively; and the degradation rates of NF, NF + Vit E, CNF, and CNF + Vit E were 29.57 ± 5.06%, 33.78 ± 7.8%, 14.03 ± 7.52%, 43 ± 6.27%, respectively. The antibacterial properties demonstrated that CNF impregnated with antibiotics reduced Escherichia coli (E. coli) counts by approximately 27–28% and Staphylococcus aureus (S. aureus) counts by about 34–35% compared to negative control. In conclusion, cross-linked Ze/Gel/CS/PVA nanofibrous scaffolds loaded with Vit E have potential as suitable wound dressing materials because environmentally friendly materials contribute to sustainable wound care and controlled degradation ensures wound dressings breakdown harmlessly.

Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells.

Purpose: Corneal fibroblasts are involved in the wound healing of the cornea with proliferation, migration, and differentiation processes. Coenzyme Q10 (CoQ10) and vitamin E can enhance corneal wound healing when applied after a corneal lesion as an eye drop. Thus, this study was performed to determine the potential efficiency of a CoQ10 ophthalmical solution containing a CoQ10 and vitamin E D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-derived formulation in human corneal fibroblasts (HCFs) in vitro. Methods: Primary HCFs were obtained from cadaveric corneal tissue, and cell viability was determined using MTT assay at 24 and 72 h. Cell migration was evaluated using an in vitro wound healing assay, and mRNA expressions of collagen type I (COL-I), collagen type III (COL-III), lumican, hyaluronan, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitors of MMP (TIMP)-1, TIMP-2, interleukin (IL)-1β, IL-6, IL-8, and IL-10 were assessed using reverse transcription polymerase chain reaction at 24 and 72 h. Results: At various concentrations of CoQ10 ophthalmical solution (CoQ10-os), cell viability and wound healing rates of HCFs increased compared with the control group. The expressions of COL-I, COL-III, lumican, and hyaluronan were increased by CoQ10-os, whereas those of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were not affected by CoQ10-os at 24 and 72 h. In treating HCFs with a CoQ10-os medium, IL-1β, IL-6, and IL-8 decreased, whereas IL-10 was significantly increased in a time- and dose-dependent manner. Conclusions: The findings indicate that CoQ10 and vitamin E-TPGS are potent regulators of the bioactivity of HCFs, thus supporting their potential application as ophthalmical solutions in therapies aimed at the fast regeneration of damaged cornea tissues.

Vitamin-E TPGS Based Microemulsion: An Approach for Solubility Enhancement of Poorly Water-Soluble Drugs

Poor aqueous solubility is the primary concern for dissolving new drug substances during early development. Several novel solubility enhancement techniques such as particle size reduction, salt formation, making solid dispersion, complex formation, use of cosolvent techniques, use of surfactants, physical and chemical modification, and PH adjustment using buffering agents have been explored extensively to resolve the issue of poor aqueous solubility of drug substances. Drug delivery in micro and nano-sized formulations is one of the ways to improve the solubility of these drug candidates over the physiological pH range. In recent years, combination methods have also been considered an interesting approach where more than one solubility enhancement technique is used. The present review focuses on the feasible approach for improving the solubility by forming Vitamin E TPGS-based suspension in micro or nano form by particle size reduction. Further, by granulation or spray drying techniques, these suspensions converted to a solid dosage form for oral drug delivery for patient compliance are being explore

In vitro dissolution/permeation tools for amorphous solid dispersions bioavailability forecasting I: Experimental design for PermeaLoop™

Along with the increasing demand for candidate-enabling formulations comes the need for appropriate in vitro bioavailability forecasting. Dissolution/permeation (D/P) systems employing cell-free permeation barriers are increasingly gaining interest, due to their low cost and easy application as passive diffusion bio-predictive profiling in drug product development, as this accounts for nearly 75% of new chemical entities (NCEs) absorption mechanism.To this end, this study comprises theoretical considerations on the design and experimental work towards the establishment and optimization of a PermeaLoop™ based dissolution/permeation assay to simultaneously evaluate the drug release and permeation using Itraconazole (ITZ)-based amorphous solid dispersions (ASD) formulations, with different drug loads, based on a solvent-shift approach. Alternative method conditions were tested such as: donor medium, acceptor medium and permeation barrier were screened using both PermeaPad® and PermeaPlain® 96-well plates. A range of solubilizers, namely Sodium Dodecyl Sulfate, Vitamin E-TPGS and hydroxypropyl-β-cyclodextrin, were screened as possible solubilizing additives to the acceptor medium, while donor medium was varied between blank FaSSIF (phosphate buffer) and FaSSIF. The method optimization also included the ITZ dose selection, being the ITZ single dose (100 mg) considered the most adequate to be used in further experiments to allow the comparison with in vivo studies.In the end, a standardized approach that may be applied to predict the bioavailability of weakly basic poorly soluble drug-based formulations is described, contributing to strengthening the analytical portfolio of in vitro pre-clinical drug product development.

Off-Label use of Raloxifene hydrochloride in uterine fibroids: A novel insert-based formulation approach and IN-VIVO preclinical evaluation

Most available uterine fibroids (UF) treatments are invasive and administered through either oral or parenteral routes. Raloxifene hydrochloride (RLH), a selective estrogen receptor modulator, is chosen as a drug of choice. Currently, it is used in the prevention and treatment of osteoporosis. However, RLH in recent clinical trials on UF shows a significant reduction in the size of UF; therefore, the present work is proposed to use RLH for its off-label use for the treatment of UF. This research aimed to formulate an RLH-loaded drug eluting insert (DEI) and study its uterine-targeting efficiency after intrauterine administration. Capsular-shaped biodegradable insert was prepared by melting method. PCL was selected as the rate-controlling polymer, while PEG 4000 and Vitamin ETPGS were selected as solubilizers. The insert was characterized using SEM, FTIR, XRD, and DSC and evaluated for mechanical strength, drug loading, in-vitro drug release, in-vivo evaluation, and histology studies. The results signify no interference between the drug and excipients in designing the RLH insert. The drug release showed up to 45–50% in 15 days with the desired degradation. In a healthy New Zealand white female rabbit, uterus fibroid was induced by Diethylstilbestrol. The uterus fibroid was confirmed by ultrasonography before the insertion of the implant surgically. The therapeutic effects of Raloxifene were evaluated based on detecting fibroid shrinkage at specific intervals and tissue histology at the end of the study. The Raloxifene-treated rabbits showed positive therapeutic results in comparison to placebo and untreated animals. Preclinical in vivo results show the biodegradation of DEI with a significant reduction in the size of UF. Uterine targeting of RLH-insert was successfully designed and evaluated for its off-label use in the treatment of UF through intrauterine targeting via. Vaginal route. Drug targeting to the site of action anticipates the dose reduction desired to elicit the therapeutic outcome and overcome the side effects of existing therapies.

Utilizing TPGS for Optimizing Quercetin Nanoemulsion for Colon Cancer Cells Inhibition

Background: Colorectal cancer is one of the most challenging cancers to treat. Exploring novel therapeutic strategies is necessary to overcome drug resistance and improve patient outcomes. Quercetin (QR) is a polyphenolic lipophilic compound that was chosen due to its colorectal anticancer activity. Nanoparticles could improve cancer therapy via tumor targeting by utilizing D-tocopheryl polyethylene glycol succinate (vitamin-E TPGS) as a surfactant in a nanoemulsion preparation, which is considered an efficient drug delivery system for enhancing lipophilic antineoplastic agents. Thus, this study aims to develop and optimize QR-loaded nanoemulsions (NE) using TPGS as a surfactant to enhance the QR antitumor activity. Method: The NE was prepared using a self-assembly technique using the chosen oils according to QR maximum solubility and TPGS as a surfactant. The prepared QR-NE was evaluated according to its particle morphology and pH. QR entrapment efficiency and QR in vitro drug release rate were determined from the selected QR-NE then we measured the QR-NE stability. The anticancer activity of the best-selected formula was studied on HT-29 and HCT-116 cell lines. Results: Oleic acid was chosen to prepare QR-NE as it has the best QR solubility. The prepared NE, which had particles size < 200 nm, maximum entrapment efficiency > 80%, and pH 3.688 + 0.102 was selected as the optimal formula. It was a physically stable formula. The prepared QR-NE enhanced the QR release rate (84.52 ± 0.71%) compared to the free drug. QR-NPs significantly improved the cellular killing efficiency in HCT-116 and HT-29 colon cancer cell lines (lower IC50, two folds more than free drug). Conclusion: The prepared QR-NE could be a promising stable formula for improving QR release rate and anticancer activity.

Osmolality of Excipients for Parenteral Formulation Measured by Freezing Point Depression and Vapor Pressure - A Comparative Analysis.

To investigate the difference in methods to determine the osmolality in solutions of stabilizers used for long-acting injectable suspensions. The osmolality was measured by freezing point depression and vapor pressure for 11 different polymers and surfactants (PEG 3350, 4000, 6000, 8000, 20,000, PVP K12, K17 and K30, poloxamer 188, 388 and 407, HPMC E5, Na-CMC, polysorbate 20 and 80, vitamin E-TPGS, phospholipid, DOSS and SDS) in different concentrations. Independently of the measuring method, an increase in osmolality with increasing concentration was observed for all polymers and surfactants, as would be expected due to the physicochemical origin of the osmolality. No correlation was found between the molecular weight of the polymers and the measured osmolality. The osmolality values were different for PVPs, PEGs, and Na-CMC using the two different measurement methods. The values obtained by the freezing point depression method tended to be similar or higher than the ones provided by vapor pressure, overall showing a significant difference in the osmolality measured by the two investigated methods. For lower osmolality values (e.g. surfactants), the choice of the measuring method was not critical, both the freezing point depression and vapor pressure could be used. However, when the formulations contained higher concentrations of excipients and/or thermosensitive excipients, the data suggests that the vapor pressure method would be more suited.

Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Resveratrol loaded polymeric micelles for theranostic targeting of breast cancer cells.

Treatment of breast cancer underwent extensive progress in recent years with molecularly targeted therapies. However, non-specific pharmaceutical approaches (chemotherapy) persist, inducing severe side-effects. Phytochemicals provide a promising alternative for breast cancer prevention and treatment. Specifically, resveratrol (res) is a plant-derived polyphenolic phytoalexin with potent biological activity but displays poor water solubility, limiting its clinical use. Here we have developed a strategy for delivering res using a newly synthesized nano-carrier with the potential for both diagnosis and treatment.Methods: Res-loaded nanoparticles were synthesized by the emulsion method using Pluronic F127 block copolymer and Vitamin E-TPGS. Nanoparticle characterization was performed by SEM and tunable resistive pulse sensing. Encapsulation Efficiency (EE%) and Drug Loading (DL%) content were determined by analysis of the supernatant during synthesis. Nanoparticle uptake kinetics in breast cancer cell lines MCF-7 and MDA-MB-231 as well as in MCF-10A breast epithelial cells were evaluated by flow cytometry and the effects of res on cell viability via MTT assay.Results: Res-loaded nanoparticles with spherical shape and a dominant size of 179±22 nm were produced. Res was loaded with high EE of 73±0.9% and DL content of 6.2±0.1%. Flow cytometry revealed higher uptake efficiency in breast cancer cells compared to the control. An MTT assay showed that res-loaded nanoparticles reduced the viability of breast cancer cells with no effect on the control cells.Conclusions: These results demonstrate that the newly synthesized nanoparticle is a good model for the encapsulation of hydrophobic drugs. Additionally, the nanoparticle delivers a natural compound and is highly effective and selective against breast cancer cells rendering this type of nanoparticle an excellent candidate for diagnosis and therapy of difficult to treat mammary malignancies.

A novel method for preparing stabilized amorphous solid dispersion drug formulations using acoustic fusion.

A diverse set of drug and polymer combinations have been effectively evaluated utilizing a newly developed method called acoustic fusion to form amorphous solid dispersions (ASD) on the mg-scale, indicating that this approach is a general procedure that can be applied for ASD drug formulations. We have demonstrated the effectiveness of this acoustic fusion process by generating amorphous solid dispersions of various BCS class 2 and 4 drug candidates, including torcetrapib, itraconazole, and lopinavir, with a variety of polymer systems, including HPMCAS (L, M, and H), copovidone, Soluplus®, PEG1500, Vitamin-E TPGS, Kolliphor EL, and Eudragit, etc. Formulations of these ASD drug products demonstrated significantly elevated solubility of the drug substance compared to the solubility of the crystalline form of the drug. Acoustic fusion products using the model drug torcetrapib in either HPMCAS-LF, copovidone + Vitamin-E TPGS, or Soluplus®, exhibited enhanced supersaturation solubility in aqueous buffer in vitro compared to the drug in crystalline form, indicating that the acoustic fusion process resulted in an amorphous solid dispersion state similar to those formed in spray drying (SD) or hot melt extrusion (HME) processes. In vivo dosing of formulations of the acoustic fusion products in a rat pharmacokinetic study at a dose level of 10 mg/kg resulted in an improvement in exposures of approximately 8-fold by AUC(0-24) in comparison to a conventional suspension formulation of the drug material in crystalline form, thus validating the efficiency of this novel acoustic fusion approach for elevating the bioperformance in preclinical studies.

Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.

MRP2-mediated transport of etoposide in MDCKII MRP2 cells is unaffected by commonly used non-ionic surfactants.

The aim of the present study was to investigate the ability of non-ionic surfactants to inhibit MRP2-mediated transport in vitro in MDCKII MRP2 cells. Transport studies across MDCKII MRP2 cell monolayers were performed using 3H-etoposide and 3H-digoxin. 19 different non-ionic surfactants, including several polysorbates (PS), cremophor EL, vitamin E-TPGS, and n-nonyl β-D-glucopyranoside (NG), were investigated. Barrier function of the cells was investigated measuring TEER and transport of 14C-glycine. The amount of isotope was quantified using liquid scintillation counting. In MDCKII MRP2 cells a polarized transport of etoposide and digoxin in the secretory (basolateral to apical) direction with efflux ratios of 5.5 ± 0.7 and 18.5 ± 4.2, respectively, was measured. P-gp inhibitors such as valspodar and zosuquidar did not affect etoposide transport, and furthermore PS20 decreased secretory transport of digoxin, but not of etoposide. Transport of etoposide was therefore mainly MRP2-mediated and used as a probe to investigate pharmaceutical excipients. Non-ionic surfactants did not modulate etoposide transport across intact cell monolayers of MRP2 overexpressing MDCKII cells, although preliminary studies suggest that most were able to alter MRP2-mediated efflux of the fluorescent 5-chloromethylfluorescein (CMF). In conclusion, etoposide transport across MDCKII MRP2 cells was modulated by cyclosporin A, an inhibitor of MRP2 and P-gp, but not by specific P-gp inhibitors (valspodar and zosuquidar), which suggests that etoposide transport is primarily influenced by MRP2. In addition, commonly used non-ionic surfactants did not decrease MRP2-mediated etoposide transport in MDCKII MRP2 cells. These results suggest that etoposide transport in MDCKII MRP2 cells is a model system to investigate MRP2 interactions, and that surfactants may not have a large potential for increasing oral bioavailability of drugs through inhibition of MRP2 transport activity.

Antifungal efficacy of Itraconazole loaded PLGA-nanoparticles stabilized by vitamin-E TPGS: In vitro and ex vivo studies

Itraconazole (ITZ) loaded Poly-(D, L-lactic-co-glycolic acid, PLGA) nanoparticles (PLGA-NPs) stabilized by D-α-Tocopherol polyethylene-glycol succinate-1000 (TPGS) were developed by nanoprecipitation and single emulsion solvent evaporation methods to improve antifungal activity of ITZ by enhancing its solubility, and hence bioavailability. Encapsulation efficiency, drug loading, in-vitro release, ex-vivo permeation and antifungal activity were performed for the optimized PLGA-NPs. Characterization of PLGA-NPs were performed by scanning electron microscopy, dynamic light scattering, differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. We observed that nanoprecipitation method was more efficient in encapsulating ITZ by using 0.3% TPGS (stabilizer) than single emulsion solvent evaporation method. Our thermal analysis studies showed no characteristic peaks for crystalline ITZ, indicating drug efficiently encapsulated inside the nanoparticle with no compatibility issues. Drug loaded PLGA-NPs preserved the antifungal activity of ITZ against Candida albicans. Drug release profile from the NPs showed an initial burst release followed by an extended release phase suggesting the potential of NPs for sustained release applications. Furthermore, ITZ encapsulated in PLGA-NPs showed enhanced intestinal permeability in the ex-vivo study. In conclusion, the developed nano-system successfully encapsulated ITZ, yielding an increased permeation and consequential antifungal activity.

Integrating the drug, disulfiram into the vitamin E-TPGS-modified PEGylated nanostructured lipid carriers to synergize its repurposing for anti-cancer therapy of solid tumors

The ‘repurposed drug,’ disulfiram (DSF), is an inexpensive FDA-approved anti-alcoholism drug with multi-target anti-cancer effect. However, the use of DSF in clinical settings remains limited due to its high instability in blood. In the present study, we created nanostructured lipid carriers (NLC) encapsulated DSF modified with d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E-TPGS). A spherical shape, superior drug encapsulation (80.7%), and decreased crystallinity of DSF were confirmed with results obtained from TEM, XRD, and DSC analysis. Addition of TPGS considerably improved the physicochemical stability profile of NLC-encapsulated DSF under the different conditions tested here. Furthermore, TPGS-DSF-NLCs outperformed unmodified DSF-NLCs and the free DSF solution by having significantly higher cytotoxicity, lower IC50 value (4T1: 263.2 nM and MCF-7: 279.9 nM), and an enhanced cellular uptake in MCF7 and 4T1 cell lines. In vivo anti-tumor analysis in 4T1 murine xenograft model mice revealed a significant (p-value < 0.05) decrease in tumor volume and higher tumor growth inhibition rate (48.24%) with TPGS-DSF-NLC treatment as compared to both the free DSF solution (8.49%) and DSF-NLC formulations (29.2%). Histopathology analysis of tumor tissues further confirmed a noticeably higher anti-tumor activity of TPGS-DSF-NLC through augmented cell necrosis in solid tumors. Hence, the present study established that addition of TPGS can synergize the anti-cancer activity of NLC-encapsulated DSF formulations, and thus, offer a promising anti-cancer delivery system for DSF.

Fabrication of surfactant-stabilized nanosuspension of naringenin to surpass its poor physiochemical properties and low oral bioavailability

BackgroundNanosuspension is a biphasic system consisting of native drug particles dispersed in an aqueous surfactant or polymeric solution with a particle size between 10 to 1000 nm. In contrast to other drug delivery systems, nanosuspension offer the unique advantage of increasing solubility of the native drug resulting into faster drug absorption and hence achieving faster maximum plasma concentration. Hypothesis/PurposeThe present study aims to evaluate surfactants/polymer stabilized nanosuspensions of naringenin (NN), a phytomedicine, to surpass its poor physiochemical properties and low oral bioavailability. Study designOptimization and characterization (DLS, SEM, PXRD and DSC) of nanosuspensions followed by in-vitro drug dissolution studies and pharmacokinetic study in male Sprague–Dawley rats were performed. MethodsNanosuspensions were prepared by precipitation-ultrasonication method with varying concentrations of different surfactants and polymer such as sodium cholate (SC), sodium lauryl sulphate (SLS), poly ethylene glycol 4000 (PEG), polysorbate 80 (Tween® 80), poloxomer-188 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS or Vitamin E-TPGS). ResultsNanosuspension prepared with 0.5% w/v d-α-Tocopherol polyethylene glycol 1000 succinate (TPNS) and 7.5 mg NN, showed the smallest size of 118.1 ± 2.7 nm. TPNS showed increase in drug dissolution in simulated gastric fluid pH 1.2 (SGF) and phosphate buffer pH 6.8 (PB). TPNS demonstrated an improved pharmacokinetic profile compared to pure NN resulting 2.14 and 3.76 folds increase in Cmax and AUC, respectively. In addition, TPNS were stable over a period of six months. ConclusionThe developed formulation strategy of nanosuspension could be exploited to improve the solubility and bio-availability of poorly soluble NN and other phytomedicines.

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy

Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization.Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35–60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02μm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers.Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.

Fabrication and Appraisal of Poly (Lactic-Co-Glycolic Acid) - Moxifloxacin Nanoparticles using Vitamin E-TPGS: A Potential Intracanal Drug Delivery Agent.

Nanotechnology is gaining momentum in the search for ideal biomaterials by dental researchers. The expansible nature of Endodontology deems exploration, learning and scrutinizing newer avenues which have the potential to be applied and investigated. The popularity of polymers as drug delivery vehicles has opened avenues for their application in the root canal system. This study utilized application of biodegradable polymers as potential drug delivery vehicles against Enterococcus faecalis, one of the main reasons for post treatment disease. This study aimed at fabricating Poly (Lactic-co-Glycolic Acid) (PLGA)-moxifloxacin nanoparticles and assessing its sustained antimicrobial efficacy with calcium hydroxide and chitosan-moxifloxacin hydrogel against Enterococcus faecalis. PLGA (50:50) in a quantity of 100 mg was dissolved in 1 ml ethyl acetate and 45 ml of 0.3% w/v Vitamin-E Polyethylene Glycol 1000 Succinate (vitamin E-TPGS) was kept for magnetic stirring in separate beaker. Moxifloxacin (50 μl) was added to polymer PLGA following which vitamin E-TPGS was added to the polymer. Nanoparticles were fabricated using ultrasonication and collected by centrifugation. Surface characterization was assessed using scanning electron microscope. Results were obtained in the form of zone of inhibition by the nanoparticles against Enterococcus faecalis and comparisons were made with chitosan-moxifloxacin hydrogel and calcium hydroxide using Analysis of Variance (ANOVA) followed by Student t-test. Upon statistical analysis, the zone of inhibition against E. faecalis remained constant with PLGA-moxifloxacin nanoparticles for 14 days while it decreased with chitosan-moxifloxacin hydrogel and remained nil for calcium hydroxide (p<0.01). The study posits that PLGA encapsulated moxifloxacin nanoparticles showcased sustained antibacterial effect in low doses against the test pathogen. Its sustained and programmed release makes them unique contenders for further evaluation in Endodontics as potential intracanal medicaments.

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 μg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/d-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment.

Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-d-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7 μM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7 μM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial–mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment.

Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin.

In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5-38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2-2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.