Nontoxic Vehicle Research Articles

Data-Driven Approaches to Predict Dendrimer Cytotoxicity.

Dendrimers are employed as functional elements in contrast agents and are proposed as nontoxic vehicles for drug delivery. Toxicity is a property that is to be evaluated for this novel class of bionanomaterials for in vivo applications. The current research is hampered due to the lack of structured data sets for toxicity studies for dendrimers. In this work, we have built a data set by curating literature for toxicity data and augmented it with structural and physicochemical features. We present a comprehensive, feature-rich database of dendrimer toxicity measured across various cell lines for prediction, design, and optimization studies. We have also explored novel computational approaches for predicting dendrimer cytotoxicity. We demonstrate superior outcomes for toxicity prediction using essential regression in the space of small data sets.

Prediction of drug-carrier interactions of PLA and PLGA drug-loaded nanoparticles by molecular dynamics simulations

In the field of drug delivery, biodegradable polymeric nanoparticles have attracted a great deal of research interest due to their potential as an ideal non-toxic vehicle for the delivery of active compounds in a controlled and targeted manner. However, at the stage of academic and industrial development, the lack of regulatory instructions for the assessment and characterization of those nanometric materials is considerably delaying their clinical success if compared to other macroscopic systems (i.e. microparticles). In fact, owing to their high surface area to volume ratio, unwanted interactions between nanoparticles and biological systems may occur, leading to unexpected toxicity. In addition, knowledge of drug-polymer interactions is compulsory, as they can directly affect many fundamental properties, such as the drug-loading ability, nanoparticle size, the drug physical state and stability, as well as the actual drug release profile.In this context, computational methods able to rapidly predict the binding and dynamics between drug molecule and its carrier, and between the carrier and biological systems, are highly desirable to minimize the investment in drug design and development. In this study a full atomistic molecular dynamics simulation approach was validated to investigate biomolecular behaviour of poly (lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA) as nanoparticulate drug delivery systems. Both polymer systems have been firstly investigated without drugs to better observe their tendency to interact with aqueous solution, which represents a crucial point for drug delivery systems. Subsequently, simulations were run after the incorporation of drugs. Paracetamol, Prednisolone, and Isoniazid were chosen as model drugs in relation to their different affinity with lipids. Specific interactions between polymers and drugs were considered, and a direct comparison between computational results and experimental evidences found in literature was carried out.

PH-sensitive ternary Fe3O4/GQDs@G hybrid microspheres; Synthesis, characterization and drug delivery application

In this work, a simple approach used to develop new ternary gelatin-coated magnetite/graphene quantum dots hybrid microspheres (Fe3O4/GQDs@GM) as an anticancer drug carrier. Moreover, a neat gelatin microsphere (GM) was prepared to compare the performance of both prepared systems. Prepared samples were identified by using fourier transform infrared (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analysis. photoluminescence (PL) analysis approved the PL property for the Fe3O4/GQDs@GM, as well as, the vibrating sample magnetometer (VSM) exhibited superparamagnetic properties for it. Study the in vitro biodegradation behavior of ternary Fe3O4/GQDs@GM in the trypsin approved its enzymatic degradation capability. 30.15% and 22.29% of curcumin (CUR) as a natural anticancer drug respectively was loaded in Fe3O4/GQDs@GM and GM. The drug release test at two different pH (7.4 and 5.0) showed the pH-sensitive drug release pattern. The biocompatibility of the prepared microspheres was confirmed by calculation the viability of the breast cancer cell (MDA-MB 231) after treatment with each microsphere. DAPI staining test revealed apoptosis on MDA-MB 231 cancer cells that treated with the drug-loaded microspheres. The results of the drug delivery and biological studies revealed an improved performance for ternary Fe3O4/GQDs@GM, therefore, it could be proposed as a biodegradable, pH-sensitive, and non-toxic vehicle for anticancer drug delivery.

Luminescent chitosan/carbon dots as an effective nano-drug carrier for neurodegenerative diseases.

Designing new materials for effective and targeted drug delivery is pivotal in biomedical research. Herein, we report on the development of a chitosan/carbon dot-based nanocomposite and investigate its efficacy as a carrier for the sustained release of dopamine drug. The carbon dots (CDs) were synthesized from the carbonization of chitosan and were further conjugated with chitosan (CS) to obtain a chitosan/carbon dot (CS/CD) matrix. Dopamine was later encapsulated in the matrix to form a dopamine@CS/CD nanocomposite. The cytotoxicity of IC-21 and SH-SY5Y cell lines was studied at various concentrations of the nanocomposite and the results demonstrate around 97% cell viability. The photoluminescence property revealed the characteristic property of the carbon dots. When excited at 510 nm an emission peak was observed at 550 nm which enables the use of carbon dots as a tracer for bioimaging. The HRTEM images and the D, G, and 2D bands of the Raman spectra confirm the successful synthesis of carbon dots and through DLS the particle size is estimated to be ∼3 nm. The release studies of the encapsulated drug from the composite were analyzed in an in vitro medium at different pH levels. The novelty of this method is the use of a non-toxic vehicle to administer drugs effectively towards any ailment and in particular, the carbon dots facilitate the consistent release of dopamine towards neurodegenerative diseases and tracing delivery through bioimaging.

Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles

Three novel polycationic gemini amphiphiles with different spacers were developed and evaluated in terms of their physiochemical properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine® 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA). We demonstrated that the cationic liposomes 2X6/DOPE and 2X7/DOPE are potential non-toxic vehicles for gene delivery.

Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.

This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.

55. Remote control CPAs delivery via cryonanoliposomes

Whole organ preservation remains one of the greatest challenges in cryobiology. The main approaches to organ preservation such as hypothermic storage, supercooling, and vitrification each suffer from limitations including short timescales for preservation, ice crystal formation, mechanical and thermal stresses, cryoprotectant toxicity, etc. Liposomes are non-toxic, biodegradable and non-immunogenic drug delivery vehicles that are approved by the US FDA (1995). Liposomes are still among the most widely used nanoparticles as drug delivery systems and they are suitable for delivering both hydrophilic and lipophilic agents. Despite their widespread use in diverse fields, this technology has not been widely applied in the field of cryopreservation. We propose a CPA delivery system which can achieve targeted delivery of cryoprotectant agents (CPAs) to the intracellular or extracellular environment, while also serving as a means to deliver CPAs to a specific cell type within complex tissues. Furthermore, our proposed CPA delivery system will utilize controlled and timed release of CPAs which will allow delivery at specific time points throughout the freezing and thawing process. Ultrasonic and electromagnetic waves can be used to manipulate the release profile of CPA-loaded liposomes and their release profile can be fine-tuned based on liposomal characteristics such as phospholipid type and saturation. We anticipate several applications for controlled, timed release of CPAs. For example, vitrification involves high concentrations of toxic CPAs which must be loaded at low temperatures and be washed from the system after preservation in order to reduce toxicity. Our system will allow liposomes to be perfused at relatively higher temperatures and the release of their contents would be activated at relatively lower temperatures, improving uniform distribution and reducing toxicity. Other examples include the timed release of enzymes during rewarming which would degrade toxic CPAs such as DMSO thereby reducing CPA toxicity, or endothermic reactants, which could help with temperature uniformity during cooling. Finally, encapsulation of vital energy substrates (e.g. glucose) and their timed release during the earlier phases of thawing process may aid in meeting challenges associated with rewarming.

Enhanced photochemical nitric oxide release from a flutamide derivative incorporated in Pluronic F127 micelles

The incorporation of nitric oxide (NO) photodonors into nontoxic vehicles may allow for the tunable control of topical NO release to treat pathological conditions associated with the impairment of NO production in the dermal vasculature. Pluronic F127 is a PEO–PPO–PEO triblock copolymer that is used as a nontoxic vehicle that undergoes thermally reversible micellization and gelation. In this study, we synthesized a thermally stable flutamide derivative, N-(3-aminopropyl)-3-(trifluoromethyl)-4-nitrobenzenamine (ATN), which is capable of releasing NO upon irradiation with visible light, as shown by real-time chemiluminescence NO detection. We demonstrated that the incorporation of ATN into the hydrophobic nuclei of F127 micelles leads to an enhancement of its photochemical NO release, which is consistent with the photodecomposition route associated with the nitro-to-nitrite photorearrangement of ATN. This mechanism underscores a new role of the F127 micelles as concentrating “nanoreactors” for hydrophobic NO releasing drugs. In this case, this effect may represent a new strategy for enhancing photochemical NO release from ATN, which makes the micellar F127/ATN solutions promising for topical NO application.

Lipid nanoparticles protect from edelfosine toxicity in vivo

Edelfosine, an alkyl-lysophospholipid antitumor drug with severe side-effects, has previously been encapsulated into lipid nanoparticles (LN) with the purpose of improving their toxicity profile. LN are made of lipids recognized as safe by the Food and Drug Administration (FDA) and, therefore, these systems are generally considered as nontoxic vehicles. However, toxicity studies regarding the use of LN as vehicles for drug administration are limited. In the present study, we investigated the in vivo toxicity of free edelfosine, and the protection conferred by LN. The free drug, non-loaded LN and edelfosine-loaded LN were orally administered to mice. Our results show that the oral administration of the free drug at 4 times higher than the therapeutic dose caused the death of the animals within 72h. Moreover, histopathology revealed gastrointestinal toxicity and an immunosuppressive effect. In contrast, LN showed a protective effect against edelfosine toxicity even at the higher dose and were completely safe. LN are, therefore, a safe vehicle for the administration of edelfosine by the oral route. The nanosystems developed could be further used for the administration of other drugs.

Two-site diamond-like point defects as new single-photon emitters

In this small review, we recall two promising candidates for biomarker nanosystems, in which a two-site defect embedded in a diamond-like lattice makes a single-photon source. The two candidates are the silicon-vacancy defect in diamond, and the carbon antisite-vacancy pair in 4H silicon carbide.These defects, which by symmetry resemble to the famous nitrogen-vacancy defect in diamond, bear an exact or nearly exact C 3v symmetry, giving them selection rules which lead their important magnetooptical properties. The embedding diamond-like crystal lattice not only determines the symmetry of two-site defects, but also ensure a nontoxic vehicle on which they reside; a definitive requirement against biomarker nanosystems.In the silicon-vacancy case, the size of the biomarker system is also an important feature. Nanoparticles of the embedding crystal do not exceed the size of molecular clusters, in order to be able to aid measuring all types of relevant biomolecular processes.

Enhancement of gene transfer efficiency in the Bcap-37 cell line by dimethyl sulphoxide and menthol

Simple and efficient gene transfer into the nucleus would facilitate non-viral gene delivery. One promising method of non-viral gene delivery is to apply penetration enhancers. Chemicals, such as dimethyl sulfoxide (DMSO) and menthol, may have promise as non-toxic vehicles in improving gene transfer efficiency. In this study, the cytotoxic effects of DMSO and menthol were evaluated using MTT assays. Gene delivery efficiency in a human breast cancer cell line (Bcap-37) was investigated by quantitative PCR, fluorescence microscopy and flow cytometry. Non-toxic concentrations of DMSO (2%) and menthol (12.5µM) enhanced the efficiency of liposome-mediated gene delivery in Bcap-37 cells. Quantitative PCR results showed that growth hormone (GH) mRNA expression in the post-menthol and pre-DMSO treatment groups was 10-fold higher compared to that in the liposome group, while in the pre-menthol and post-DMSO treatment groups, a 30-fold increase in GH mRNA expression was observed. Both DMSO and menthol treatments increased green fluorescent protein (GFP) expression efficiency as shown by fluorescence microscopy experiments. Compared to the liposome group, the number of positive cells in the pre-menthol and post-DMSO treatment groups was significantly increased by 15%. Furthermore, cell cycle analysis demonstrated that there were significant differences among the DMSO-treated group, the menthol-treated group and the normal group, which implied different effects of DMSO and menthol treatments. In conclusion, both non-toxic and harmless DMSO (2%) and menthol (12.5µM) treatments improve gene transfer efficiency, while post-DMSO treatment may be the most effective protocol in increasing transgene expression efficiency.

Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice

Routine laboratory procedures, such as handling or transporting animals or carrying out injections on animals, are stressful for animals but are necessary in many pre-clinical studies. Here, the authors show that multiple injections of the non-toxic vehicle cyclodextrin moderately increased plasma corticosterone concentrations in female BALB/c mice. Additionally, male BALB/c mice that had received a single intraperitoneal injection of harmless saline had an increased glucocorticoid response to a second saline injection. The authors found that female mice that had been exposed to an acute psychological stress session had a decreased glucocorticoid response to a second homotypic stressor. In contrast, multiple psychological stress sessions led to increased glucocorticoid release in female mice. Acute injection(s) of saline in male mice and of cyclodextrin in female mice led to transient lymphocytopenia. Further analysis showed that repeated stress-induced lymphocytopenia is glucocorticoid-dependent. The authors conclude that laboratory stress can affect physiological parameters in mice, potentially altering study results.

Double-shell gold nanoparticle-based DNA-carriers with poly- l-lysine binding surface

In view of the prospective applications of polyamine coatings in functional gold nanoparticles for use as carriers in gene delivery systems, in tissue repair and as bactericidal and virucidal non-toxic vehicle, we have investigated the interactions of poly- l-lysine (PLL) with gold nanoparticles (AuNP). Since direct binding of PLL to AuNP is not strong at neutral pH, we have focused on PLL interactions with carboxylated self-assembled monolayers (SAM) on AuNP, such as the citrate-capped AuNP. The double-shell nanoparticles AuNP@Cit/PLL thus produced do not contain any toxic thiols. We have observed strong electrostatic interactions between polycationic chains of PLL and AuNP@Cit in weakly acidic to weakly alkaline solutions (pH 5–9), as evidenced by the bathochromic shift of the local surface plasmon (SP) band and strong increase in resonance elastic light scattering (RELS) intensity. The stoichiometry of interactions evaluated on the basis of RELS data indicates on a hyper-Langmuirian type of interactions with stoichiometric coefficient n = 1.35 (PLL : AuNP@Cit). From the RELS titration data, a shift of the deprotonation constant for the bound PLL has been determined ( pK a = 11.6 for the bound PLL vs. 10.48 for the free PLL). The deprotonation of PLL leads to AuNP aggregate disassembly, evidenced by sharp RELS decline and hypsochromic shift of SP band. We have found that under these conditions, a residual aggregation due to the interparticle interactions between β-sheets of PLL overcoat become predominant. The molecular dynamics simulations indicate that multiple hydrogen bonds can also be formed between the PLL linker and the shell molecules of AuNP@Cit. The double-shell nanoparticles, AuNP@Cit/PLL, have been shown to attract DNA molecules using highly sensitive RELS measurements presenting the proof-of-concept for the suitability of this non-toxic nanostructured material for gene delivery applications. The advantage of the proposed material is no toxicity related to the ligand release in gene delivery processes in contrast to the thiol-functionalized AuNP.

Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

BackgroundSeveral active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models.MethodsExcipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility.ResultsThe following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y® Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol.ConclusionsAs reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.

Oral administration of heat‐solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals

Sir, The paper by Narayanan et al., 20091 demonstrating the protective effect of curcumin and resveratrol in prostate cancer gives an interesting insight regarding the use of phytochemical combination therapy. It is of interest to note that liposome encapsulated curcumin was used for in vivo experimental animal use in this study to resolve the bioavailability issue of curcumin, resulting from poor absorption.1 It is very likely that poor absorption is a consequence of the fact that curcumin is practically insoluble in water. Therefore, solubility is an important issue in in vitro and in vivo experiments. Here, we would like to point out that we have shown increased solubility of curcumin (12-fold) and turmeric (3-fold) by the use of heat.2 The treatment with heat did not destroy curcumin’s biological activity, as shown by its inhibition of 4-hydroxy-2-nonenal (HNE) mediated modification (80% inhibition of HNE-modification) of a multiple antigenic peptide3 substrate in an enzyme-linked immunosorbent assay4 that employed HNE-modification of a solid-phase antigen substrate. Mass-spectrometric (matrix assisted laser desorption ionization time of flight) and spectrophotometric (400-700 nm) analysis of curcumin solubilized by heat did not demonstrate any heat-mediated disintegration of curcumin.3,5 In addition, we have also shown that curcumin solubilized in mild alkali (pH 7.6, 130 μM) also significantly inhibited HNE-antigen modification.6 It has been shown that most of the curcumin (90%) in phosphate buffered sulfate and serum free media (pH 7.2, at 37°C) was broken down in 30 min.7 The treatment with heat, however, appears to protect curcumin from breaking down faster. Heat-solubilized curcumin amounts decreased 47% in 12 h compared to starting levels, and 67% in 72 h compared to starting levels.2 Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) is the most active ingredient of turmeric obtained from the rhizome Curcuma longa.7 This yellow pigment is a polyphenol that has been shown to be efficaceous against a variety of diseases, including cancer.2,7-9 Several vehicles have been employed to deliver curcumin in vivo or topically. DMSO (dimethyl sulfoxide) has been used for curcumin administration in vivo.10 A combination of hydroxypropyl-beta-cyclodextrin and propylene glycol alginate have been found to be best with respect to solubility of curcumin and release from the vehicle11 for topical delivery of curcumin. Incorporation of curcumin in an oil-in-water microemulsion12 has also been used for topical application. Another group13 has shown the potential of poly(ethylene oxide)-b-poly(epsilon-caprolactone)micelles as an injectable formulation for efficient solubilization, stabilization, and controlled delivery of curcumin in in vitro studies. Kunwar et al.14 have attempted curcumin binding to albumin and the use of liposomes as vehicles to deliver curcumin to live cells. For delivery of drugs in vivo or topically, water is indisputably the simplest and the most non-toxic vehicle, provided the drug is soluble in aqueous medium. We have already demonstrated a significant increase in solubility of curcumin in water. Here, we suggest the possibility of considering heat-solubilized curcumin15 for future in vivo and in vitro studies.

Synthesis and Evaluation of a Series of Heterobiarylamides That Are Centrally Penetrant Metabotropic Glutamate Receptor 4 (mGluR4) Positive Allosteric Modulators (PAMs)

We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.

Selective uptake of multi-walled carbon nanotubes by tumor macrophages in a murine glioma model

Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 µg), nearly 10–20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors.

Targeted liposomal drug delivery in cancer.

Liposomes, which are biodegradable and essentially non-toxic vehicles, can encapsulate both hydrophilic and hydrophobic materials, and are utilized as drug carriers in drug delivery systems. In addition, liposomes can be used to carry radioactive compounds as radiotracers can be linked to multiple locations in liposomes. One option is the hydrated compartment inside the liposome, another the lipid core into which especially hydrophobic conjugates can be attached, and the third option is the outer lipid leaflet where molecules can be bound by covalent linkage. Delivery of agents to the reticuloendothelial system (RES) is easily achieved, since most conventional liposomes are trapped by the RES. For the purpose of delivery of agents to target organs other than RES, long-circulating liposomes have been developed by modifying the liposomal surface. Understanding of the in vivo dynamics of liposome-carried agents is required for the evaluation of the bioavailability of drugs encapsulated in liposomes. In this review, we focus on the in vivo trafficking of liposomes visualized by positron emission tomography (PET) and discuss the characteristics of liposomes that affect the targeting of drugs in vivo.

Impact of water-dispersible beadlets as a vehicle for the delivery of carotenoids to cultured cells.

Water-dispersible beadlets of carotenoids were used as supplements for human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs) and human monocytes. Stability, cellular association and cytotoxicity of the carotenoid beadlets were compared with carotenoids delivered with tetrahydrofuran (THF). Incubations with lycopene, beta-carotene, lutein and astaxanthin dissolved in THF resulted in a lower stability in the medium, lower cellular association, and a higher standard deviation. Beadlets provided 60, 4, 6, and 2 times greater accumulation of lycopene, beta-carotene, lutein and astaxanthin, respectively, by PBMCs than THF. The cellular association of carotenoids delivered by THF seems to be more carotenoid-specific than when carotenoids are delivered by beadlets. After 48 h of incubation under cell culture conditions all of the four carotenoids (1 microM) delivered by beadlets to the medium showed a reduction less than 30%. In addition, no cytotoxic effect of the carotenoid beadlets or the vehicle alone was detected in a concentration range of 0.5-5 microM. The results show that beadlets are a non-toxic vehicle for supplementing and stabilizing carotenoids in culture media offering a reasonable compromise in term of cell accumulation efficiency.

Solubilization and stabilization of carotenoids using micelles: delivery of lycopene to cells in culture.

The use of the organic cosolvents tetrahydrofuran and dimethylsulfoxide was found to be unsuitable for prostate tumor cell cultures because of solvent cytotoxicity and the poor solubility and instability of lycopene. For example, the half-life of lycopene in organic/aqueous solution was found to be less than 2 h. Therefore, a micellar preparation of lycopene was developed for the solubilization and stabilization of lycopene in cell culture media. Neither the micelles themselves nor lycopene solubilized in micelles at concentrations up to 10 microg/mL in the cell culture media produced cytotoxicity or inhibition of cell proliferation in either LNCaP human prostate cells or Hs888Lu human lung cells. Lycopene solubilized in micelles was stable for at least 96 h under standard cell culture conditions so that a constant lycopene supply could be provided to the cells. During the culture process, lycopene was taken up by LNCaP cells and reached a plateau at approximately 12 h. Micelles provide a convenient, inexpensive, and nontoxic vehicle for dissolving and stabilizing carotenes such as lycopene in tissue culture media and then delivering them to cells growing in culture.