Microemulsions and nanoemulsions modified with cationic surfactants for improving the solubility and therapeutic efficacy of loaded drug indomethacin.

In this work, a noncovalent strategy was successfully used to modify colloidal stability andin vitroandin vivoefficacy of two amphiphilic formulations of the anti-inflammatory drug indomethacin. Namely, nanoemulsions and microemulsions based on oleic acid and nonionic surfactants have been produced and compared. The influence of cationic surfactants cetyltrimethylammonium bromide and its carbamate bearing analogue on the size characteristics, stability and ability to provide prolonged action of loaded drug indomethacin has been evaluated. Adding the positively charged molecules in the surface layer of nanoemulsions and microemulsions has shown the stability increase along with maintaining the size characteristics and homogeneity in time. Moreover, the carbamate modified analogue demonstrated beneficial behavior. Indomethacin loaded in microemulsions and nanoemulsions showed prolonged-release (10%-15% release for 5 h) compared to a free drug (complete release for 5 h). The rate of release of indomethacin from nanoemulsions was slightly higher than from microemulsions and insignificantly decreased with an increase in the concentration of the cationic surfactant. For carbamate surfactant nanocarrier loaded with fluorescence probe Nile Red, the ability to penetrate into the cell was supported by flow cytometry study and visualized by fluorescence microscopy.In vitrotests on anti-inflammatory activity of the systems demonstrated that the blood cell membrane stabilization increased in the case of modified microemulsion. The anti-inflammatory activity of the encapsulated drug was tested in rats using a carrageenan-induced edema model. Nanoemulsions without cationic surfactants appeared more efficient compared to microemulsions. Indomethacin emulsion formulations with carbamate surfactant added showed slower carrageenan-induced edema progression compared to unmodified compositions. Meanwhile, the edema completely disappeared upon treatment with emulsion loaded indomethacin after 4 h in the case of microemulsions versus 5 h in the case of nanoemulsions.

Nanoemulsions containing Garcinia mangostana L. pericarp extract for topical applications: Development, characterization, and in vitro percutaneous penetration assay.

A highly stable oil-in-water nanoemulsion for topical applications, containing mangostins extracted from the pericarp of mangosteen (Garcinia mangostana L.), is a promising strategy to protect mangostins as well as to improve penetration of these important antioxidants through the skins. Nanoemulsions consisted of virgin coconut oil as the oil phase, Tween-80 and Span-80 as surfactants, and xanthan gum as the thickening agent, were prepared using the high-energy and low-energy emulsification methods. The nanoemulsions that were stable up to 28 days had oil droplet diameter of 220 nm to 353 nm and zeta potential of -46.9 mV to -63.7 mV. The accelerated stability test showed that the most stable nanoemulsions were those prepared using the low-energy emulsification method with an estimated shelf life of eleven months, composed of 11% oil phase, 17% surfactant, and 72% aqueous phase. The in vitro percutaneous penetration test for the nanoemulsion with added xanthan gum provided high cumulative skin penetration of mangostins of up to 114 µg/cm2. The results of this study indicate that virgin coconut oil-based nanoemulsions containing mangostins, prepared using the low-energy emulsification method, stabilized by xanthan gum and mixed at 40°C can prospectively be used for topical applications.

Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome.

To improve the anti-tumor effect of polyethylene glycol-modified liposome containing doxorubicin (DOX-PEG liposome), the effect of sequential administration of PEG-Span 80 niosome was investigated for Colon-26 cancer cells (C26)-bearing mice. The concept of the current study is as follows: Since both particulates would be accumulated in the tumor tissue due to the enhanced permeability and retention (EPR) effect, PEG-Span 80 niosome, mainly composed of synthetic surfactant (Span 80), would interact with DOX-PEG liposome and be a trigger to induce the release of DOX from the liposome within the tumor tissue, leading to the improvement of anti-tumor effect of DOX-PEG liposome. To find out an adequate liposome for this strategy, several PEG liposomes with different compositions were examined in terms of drug release enhancement and it was found that PEG-Span80 niosome could significantly enhance the release of calcein and DOX from a PEG liposome composed of 90% hydrogenated soybean phosphatidylcholine (HSPC) and 10% cholesterol. The sequential administration of PEG-Span 80 niosome at 24 or 48 h after dosing of DOX-PEG liposome provided a higher anti-tumor effect than the single dose of DOX-PEG liposome in the C26-bearing mice. Particularly, the 24 h-later dosing of PEG-Span 80 niosome has been found to be more effective than the 48 h-later dosing. It was also confirmed that the coexistence of PEG-Span 80 niosome with DOX-PEG liposome in 50% serum or in 50% supernatant of tumor tissue homogenate significantly increased DOX release from PEG liposome, suggesting that DOX release from DOX-PEG liposome within tumor tissue would be enhanced via the interaction with PEG-Span 80 niosome. This strategy would lead to the safer and more inexpensive chemotherapy, since it could make it possible to provide the better anti-tumor effect by utilizing the lower dose of DOX.

Amended Safety Assessment of Fatty Acyl Sarcosines and Sarcosinate Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 5 acyl sarcosines and 9 sarcosinate salts as used in cosmetics; all of these ingredients are reported to function in cosmetics as hair conditioning agents and most also can function as surfactants-cleansing agents. The ingredients reviewed in this assessment are composed of an amide comprising a fatty acyl residue and sarcosine and are either free acids or simple salts thereof. The Panel relied on relevant new data, including concentration of use, and considered data from the previous Panel report, such as the reaction of sarcosine with oxidizing materials possibly resulting in nitrosation and the formation of N-nitrososarcosine. The Panel concluded that these ingredients are safe as used in cosmetics when formulated to be non-irritating, but these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.

Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design.

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication. The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable. The design suggested 3.092 solid:liquid lipid, 2.131% surfactant and 4.757 min ultrasonication fit best to get the optimized formulation. The size of the optimized CNL was noted 124.37 ± 55.81 nm, which is in the acceptable range for brain delivery. SEM results also comply with this size range (near 150 nm) and demonstrated almost spherical and uniform particles with porous and uneven surface structures. PDI, zeta potential, entrapment efficiency and % drug release were observed as 0.201 ± 0.00, - 17.2 ± 2.35 mV, 93.62 ± 0.68% and 92.73 ± 0.06%, respectively. The NLC demonstrated initial burst release with subsequent prolonged release of drug for 48 h. Weibull kinetic equation with 0.9958 R2, minimum AIC and maximum MSC value was found best fit to explain the release behavior. The ß exponent and diffusional coefficient (n) indicated combined release mechanism with Fickian diffusion as drug release mechanism. Formulation was also found stable at different storage condition.

Statistical optimization of bile salt deployed nanovesicles as a potential platform for oral delivery of piperine: accentuated antiviral and anti-inflammatory activity in MERS-CoV challenged mice.

The objective of this paper is to confine piperine, a poor oral bioavailable herbal drug into bile salt based nano vesicles for improving its aqueous solubility, hence, its therapeutic activity. Piperine-loaded bilosomes were fabricated adopting thin film hydration technique according to 32.21 full factorial design to investigate the impact of different formulation variables on the characters of bilosomes: entrapment efficiency (EE%), particle size, and % of drug released post 8 h (Q8hr). The selected optimum formula was F2 (enclosing 1% bile salt, brij72 as a surfactant, and ratio of surfactant:cholesterol was 9:1) with desirability value 0.801, exhibiting high EE% (97.2 ± 0.8%) nanosized spherical vesicles (220.2 ± 20.5 nm) and Q8hr (88.2%±5.6). The superiority of the optimized formula (F2) over the drug suspension was revealed via ex vivo permeation study, also pharmacokinetic study denoted to the boosted oral bioavailability of piperine-loaded bilosome compared to piperine suspension. Moreover, antiviral activity and safety margin of F2 was significantly higher than that of the drug suspension. The ability of piperine to interact with the key amino acids in the receptor binding domain 4L3N as indicated by its docking configuration, rationalized its observed activity. Furthermore, F2 significantly reduce oxidant markers, inflammatory cytokines in MERS-CoV-infected mice. Hence, bilosomes can be considered as a carrier of choice for piperine with potential antiviral and anti-inflammatory activities.

Polymeric Nanoreactors as Emerging Nanoplatforms for Cancer Precise Nanomedicine.

How to precisely detect and effectively cure cancer which is defined as precise nanomedicine has drawn great attention worldwide. Polymeric nanoreactors which can in situ catalyze inert species into activated ones, can greatly increase imaging quality and enhance therapeutic effects along with decreased background interference and reduced serious side effects. After a brief introduction, the design and preparation of polymeric nanoreactors are discussed from the following aspects, that is, solvent-switch, pH-tuning, film rehydration, hard template, electrostatic interaction, and polymerization-induced self-assembly (PISA). Subsequently, the biomedical applications of these nanoreactors in the fields of cancer imaging, cancer therapy, and cancer theranostics are highlighted. The last but not least, conclusions and future perspectives about polymeric nanoreactors are given. It is believed that polymeric nanoreactors can bring a great opportunity for future fabrication and clinical translation of precise nanomedicine.

Preparation and in vitro evaluation of amphiphilic paclitaxel small molecule prodrugs and enhancement of oral absorption.

A series of novel amphiphilic paclitaxel (PTX) small molecule prodrugs, PTX-succinic anhydride-cystamine (PTX-Cys), PTX-dithiodipropionic anhydride (PTX-SS-COOH) and PTX-succinic anhydride-cystamine-valine (PTX-SS-Val) were designed, synthesized and evaluated against cancer cell lines. Compared with paclitaxel, these prodrugs contained water-soluble groups such as amino, carboxyl and amino acid, which improved the aqueous solubility of the prodrugs. More importantly, the valine was introduced in PTX-SS-Val molecule and made the molecule conform to the structural characteristics of intestinal oligopeptide transporter PEPT1 substrate. Thus the oral bioavailability of prodrug could be improved because of the mediation of PEPT1 transporter. These small molecule paclitaxel prodrugs could self-assemble into nanoparticles in aqueous solution, which effectively improved the solubility of paclitaxel, and had certain stability in pH 6.5, pH 7.4 buffer solutions and simulated gastrointestinal fluids. Some of these prodrugs, especially for PTX-Cys and PTX-SS-Val, exhibited nearly equal or slightly better anticancer activity when compared to paclitaxel. Further studies on PTX-Cys and PTX-SS-Val showed that both had good intestinal absorption in the rat single-pass intestinal perfusion (SPIP) experiments. Oral pharmacokinetic experiments showed that PTX-SS-Val could effectively improve the oral bioavailability of PTX.

Linking In Vitro Intrinsic Dissolution Rate and Thermodynamic Solubility with Pharmacokinetic Profiles of Bedaquiline Long-Acting Aqueous Microsuspensions in Rats.

Pharmacokinetic (PK) profiles of a range of bedaquiline (BDQ) long-acting injectable (LAI) microsuspensions in rats after parenteral (i.e., intramuscular and subcutaneous) administration were correlated with the in vitro intrinsic dissolution rate (IDR) and thermodynamic solubility of BDQ in media varying in surfactant type and concentration to better understand the impact of different nonionic surfactants on the in vivo performance of BDQ LAI microsuspensions. All LAI formulations had a similar particle size distribution. The investigated surfactants were d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), poloxamer 338, and poloxamer 188. Furthermore, the relevance of medium complexity by using a biorelevant setup to perform in vitro measurements was assessed by comparing IDR and thermodynamic solubility results obtained in biorelevant media and formulation vehicle containing different surfactants in varying concentrations. In the presence of a surfactant, both media could be applied to obtain in vivo representative dissolution and solubility data because the difference between the biorelevant medium and formulation vehicle was predominantly nonsignificant. Therefore, a more simplistic medium in the presence of a surfactant was preferred to obtain in vitro measurements to predict the in vivo PK performance of LAI aqueous suspensions. The type of surfactant influenced the PK profiles of BDQ microsuspensions in rats, which could be the result of a surfactant effect on the IDR and/or thermodynamic solubility of BDQ. Overall, two surfactant groups could be differentiated: TPGS and poloxamers. Most differences between the PK profiles (i.e., maximum concentration observed, time of maximum concentration observed, and area under the curve) were observed during the first 21 days postdose, the time period during which particles in the aqueous suspension are expected to dissolve.

Bile Acid Tethered Docetaxel-Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes.

In this study, we describe the engineering of sub-100 nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel (DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS, DTX-PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non-rodent species including non-human primates. We further demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next-generation chemotherapeutic.

Safety Assessment of PEGylated Alkyl Glycerides as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 60 PEGylated alkyl glycerides. PEGylated alkyl glycerides are mono-, di-, and/or triglycerides that have been modified with ethylene glycol repeat units (in the starting material form as epoxide). Most of the PEGylated alkyl glycerides are reported to function as skin-conditioning agents or surfactants. The Panel reviewed the available animal and clinical data as well as data from the 1999 report for the 5 polyethylene glycol (PEG) glyceryl cocoates and the 2012 report of PEGylated oils, to determine the safety of these ingredients. The Panel concluded these ingredients are safe in the current practices of use and concentration when formulated to be nonirritating; this conclusion supersedes the 1999 conclusion issued on 5 PEG glyceryl cocoate ingredients.

Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19.

Given the speed of viral infection spread, repurposing of existing drugs has been given the highest priority in combating the ongoing COVID-19 pandemic. Only drugs that are already registered or close to registration, and therefore have passed lengthy safety assessments, have a chance to be tested in clinical trials and reach patients quickly enough to help in the current disease outbreak. Here, we have reviewed available evidence and possible ways forward to identify already existing pharmaceuticals displaying modest broad-spectrum antiviral activity which is likely linked to their high accumulation in cells. Several well studied examples indicate that these drugs accumulate in lysosomes, endosomes and biological membranes in general, and thereby interfere with endosomal pathway and intracellular membrane trafficking crucial for viral infection. With the aim to identify other lysosomotropic drugs with possible inherent antiviral activity, we have applied a set of clear physicochemical, pharmacokinetic and molecular criteria on 530 existing drugs. In addition to publicly available data, we have also used our in silico model for the prediction of accumulation in lysosomes and endosomes. By this approach we have identified 36 compounds with possible antiviral effects, also against coronaviruses. For 14 of them evidence of broad-spectrum antiviral activity has already been reported, adding support to the value of this approach. Presented pros and cons, knowledge gaps and methods to identify lysosomotropic antivirals, can help in the evaluation of many drugs currently in clinical trials considered for repurposing to target COVID-19, as well as open doors to finding more potent and safer alternatives.

Dicationic Amino Substituted Gemini Surfactants and their Nanoplexes: Improved Synthesis and Characterization of Transfection Efficiency and Corneal Penetration In Vitro.

PURPOSE: To formulate and characterize nanoparticles from m-7NH-m gemini surfactants, synthesized by a new improved method, for non-invasive gene delivery including optimization of composition for transfection efficiency and corneal penetration. METHODS: A one-pot, solvent-free, DMAP-free method was developed for the synthesis of m-7NH-m (m = 12-18) gemini surfactant series. Lipoplexes (LPXs) and nanoplexes (NPXs) of gemini surfactant-plasmid DNA were formulated with and without DOPE helper lipid, respectively, at various charge ratios and characterized by dynamic light scattering and zeta potential measurements. Transfection efficiency, cellular toxicity, effect of DOPE and gene expression kinetic studies were carried out in A7 astrocytes by flow cytometry and confocal microscopy. Corneal penetration studies of 18-7NH-18 NPXs were carried out using 3D EpiCorneal® tissue model. RESULTS: The new synthesis method provides a two-fold improved yield and the production of a pure species of m-7NH-m without DMAP and trimeric m-7N(m)-m surfactants as impurities. Structure and purity was confirmed by ESI-MS, 1H NMR spectroscopy and surface tension measurements. Particle size of 199.80 ± 1.83 nm ± S.D. and a zeta potential value of +30.18 ± 1.17 mV ± S.D. was obtained for 18-7NH-18 5:1 ratio NPXs showed optimum transfection efficiency (10.97 ± 0.11%) and low toxicity (92.97 ± 0.57% viability) at the 48-h peak expression. Inclusion of DOPE at 1: 0.5 and 1:1 ratios to gemini surfactant reduced transfection efficiency and increased toxicity. Treatment of EpiCorneal® tissue model showed deep penetration of up to 100 µm with 18-7NH-18 NPXs. CONCLUSION: Overall, 18-7NH-18 NPXs are potential gene delivery systems for ophthalmic gene delivery and for further in vivo studies.

A Review of Sclerosing Foam Stability in the Treatment of Varicose Veins.

BACKGROUND: Varicose veins are common clinical entities. Foam sclerotherapy is a minimally invasive and simple procedure; however, the side effects, efficacy, and stability of sclerosing foam are not ideal. OBJECTIVE: To summarize the current studies on sclerosing foam stability and promote foam sclerotherapy development. MATERIALS AND METHODS: We reviewed the literature before June 2018 and included only representatives studies on sclerosing foam stability. We summarized the foam half-life time (FHT) of polidocanol (POL) under 17 preparation conditions and the FHT of sodium tetradecyl sulfate under 21 preparation conditions. The preparation conditions included various combinations of temperature, liquid-gas ratio, preparation method, etc. RESULTS: The FHT of POL varied between 40 and 4,000 seconds under different conditions. The FHT of sodium tetradecyl sulfate varied from 25.7 to 390 seconds. The higher the drug concentration, the lower the temperature required to increase foam stability. The addition of surfactant greatly increased foam stability. For different gas compositions, the FHT sequence was as follows: CO2 < CO2 + O2 < O2 < air. CONCLUSION: Foam stability can be improved by changing the preparation conditions; therefore, the role of surfactants and predictive methods for FHT are worth investigating further.

Safety Assessment of Alkyl Phosphates as Used in Cosmetics.

The Expert Panel assessed the safety of 28 alkyl phosphates and concluded that these ingredients are safe in the current practices of use and concentration when formulated to be nonirritating. The ingredients in the alkyl phosphate family share a common phosphate core structure, and vary by the identity of the alkyl chains attached therein. Most of the alkyl phosphates function as surfactants in cosmetic ingredients; however, the triesters function as plasticizers rather than surfactants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients.

Novel O/W nanoemulsions for nasal administration: Structural hints in the selection of performing vehicles with enhanced mucopenetration.

We propose novel oil-in-water nanoemulsions (O/W NEs) including PEGylated surfactants and chitosan, showing good biocompatibility and optimization for nasal administration of drugs or vaccines. The transmucosal route has been shown to be ideal for a fast and efficient absorption and represents a viable alternative when the oral administration is problematic. The critical structural features in view of optimal encapsulation and transmucosal delivery were assessed by characterizing the NEs with complementary scattering techniques, i.e. dynamic light scattering (DLS), small angle X-ray (SAXS) and neutron scattering (SANS). Combined results allowed for selecting the formulations with the best suited structural properties and in addition establishing their propensity to enter the mucus barrier. To this scope, mucin was used as a model system and the effect of adding chitosan to the NEs, as adjuvant, was investigated. Remarkably, the presence of chitosan had a positive impact on the diffusion of the NE particles through the mucin matrix. We can infer that chitosan-mucin interaction induces density inhomogeneity and an increase in the pore size within the gel matrix that enhances the PEGylated NEs mobility. The coupling of mucoadhesive and mucopenetrating agents is shown to be a promising strategy for innovative transmucosal delivery systems.

Derivation of a chronic reference dose for perfluorohexane sulfonate (PFHxS) for reproductive toxicity in mice.

Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid that was used as an industrial surfactant, but is now found as an environmental contaminant worldwide. In addition to its use as an industrial surfactant, it is a legacy contaminant from the use of aqueous film-forming foams. Despite its widespread occurrence in the environment and evidence of biological activity associated with PFHxS and similar perfluoroalkyl sulfonic acids in rodents, there is no oral toxicity value currently available from the IRIS Database. To derive an oral reference dose (RfD) for PFHxS, available toxicity studies were reviewed using a weight-of-evidence approach. A 42-day mouse reproductive study was chosen as the critical study for the derivation of the oral RfD. Benchmark dose modeling was utilized to derive a point of departure (POD) for a reduction in litter size. A 95% lower confidence limit on the benchmark dose (BMDL) of 13,900 ng/mL (serum PFHxS) was modeled for a reduction in litter size. An oral RfD for PFHxS of 4.0 ng/kg/d was calculated by conversion of the BMDL to a human equivalent oral dose using a human half-life adjusted dosimetric conversion factor and the application of a total uncertainty factor of 300. Additional research is needed to better characterize the toxicity associated with oral exposure to PFHxS and refine the development of toxicity values.

Exploration of supersaturable lacidipine ternary amorphous solid dispersion for enhanced dissolution and in vivo absorption.

Amorphous solid dispersion stands out among different formulation strategies for the improvement of dissolution rate and bioavailability via generating supersaturated drug solution, which provides a higher solubility than the crystalline counterpart, leading to a promoted intestinal absorption. Soluplus (SOL), termed as the fourth generation of solid dispersion carrier, presented a preferable effect on supersaturation maintaining and bioavailability enhancement for poorly water soluble drugs. However, some binary drug/SOL systems still suffer from insufficient dissolution and unsatisfied in vivo absorption. Thus, taking Lacidipine (LCDP) as a model drug, the aim of this study was to explore a ternary amorphous solid dispersion consisted of SOL and a surfactant to further increasing the dissolution rate and in vivo absorption. First of all, various surfactants were screened via equilibrium solubility enhancement and sodium dodecyl sulfate (SDS) was selected as the most effective candidate. Thereafter, the influence of SOL/SDS and drug/carrier weight ratio on the supersaturation maintaining was investigated. The supersaturated drug solutions were spray dried and the in vitro release, pharmacokinetic behavior as well as physical stability were investigated. It was found that although combination use of SOL and SDS did not present remarkable advantage in supersaturation maintenance in liquid state, 6-7 times higher dissolution rate under non-sink condition was noticed at SOL/SDS ratio 3:1 after spray drying, for LCDP/SOL/SDS based formulation compared to that of the binary LCDP/SOL system, which was maintained even after 92.5% humidity and 60 °C accelerated stability test. Moreover, compared to the LCDP/SOL formulation, approximately 3.3 and 3.7-fold increase in C max and AUC0-∞ was achieved with LCDP/SOL/SDS based formulation. In conclusion, the presented SDS could not only be regarded as solubility enhancer but also dissolution or bioavailability promoter, highlighting its potential application in ternary supersaturable amorphous solid dispersion for further increasing the dissolution and in vivo absorption of poorly water soluble drugs.

Highly Biocompatible Nanoparticles of Au@Fluorescent Polymers as Novel Contrast Agent for In Vivo Bimodality NIR Fluorescence/CT Imaging.

In this work, one kind of biocompatible and all-in-one dual-modal nanoprobe, based on Au nanoparticles and NIR emissive semiconducting fluorescence polymers, was developed by the one-step solvent-mediated self-assembly method for in vivo X-ray computed tomography (CT) and fluorescence bioimaging for the first time. After preparation, a series of comprehensive evaluations were performed, and the nanoprobe exhibited smart size and modification, good compatibility, inducement of autophagy, long blood circulation, unconspicuous in vivo toxicity, and excellent fluorescence/CT imaging effects. Overall, the studies in this work assuredly indicate that the synthesized Au@FP nanoparticles as a noninvasive contrast agent is suitable for in vivo fluorescence/X-ray CT bimodality biomedical imaging and diagnosis.

Understanding the Role of Sodium Lauryl Sulfate on the Biorelevant Solubility of a Combination of Poorly Water-Soluble Drugs Using High Throughput Experimentation and Mechanistic Absorption Modeling.

This study investigates the influence of surfactant sodium lauryl sulfate (SLS) on the solubility of poorly-water soluble drug substances, model Compound X and Compound Y, used in a fixed dose combination oral solid dosage form. To determine the impact of SLS concentration on the solubility of compounds X and Y, we experimentally determined the critical micelle concentration (CMC) of SLS in water, simulated gastric fluid (SGF), and fed state simulated intestinal fluid (FeSSIF) in the presence of Compound X and Compound Y using UV/Visible spectrophotometry at 25°C. The aggregation of SLS was characterized by calculating the standard Gibbs free energy of micellization in all the media investigated.  To enhance the understanding of SLS aggregation, high throughput experiments and in-vivo mechanistic modelling were used to determine the effect of increasing levels of SLS on the solubility of compounds X and Y as both single agent and combination products to be formulated into a suitable oral solid dosage form. Micellar formation of SLS is a spontaneous process as shown by the negative values of the standard free energy of micellization. The CMC of SLS in the various media investigated in the presence of compounds X and Y decreases in the following order: water> FeSSIF> SGF. However, the aggregation of SLS in the various media is overall more spontaneous in the following order: SGF>FeSSIF>water. Using high throughput experimentation and in-vivo mechanistic modelling, it was determined that a combination oral solid product of compounds X and Y will have optimum solubility and in-vivo absorption if 2 mg of SLS was used in the oral solid dosage form.  The results obtained from this study will help broaden the understanding of the micellization process involving SLS and poorly-water soluble drugs used in combination oral solid dosage forms.