Study of the Effect of Phosvitin as a Potential Carrier on the Permeation Process of Somatotropin (STH) and Corticotropin (ACTH) from Biodegradable Polymers Used as Vehicles for STH and ACTH in Semi-Solid Formulations for Skin Application.

Phosvitin shows chelating abilities, an affinity for ACTH (corticotropin), growth factors, antioxidant properties, and acidic nature. An attempt was made to use this protein in hydrogels as a transporter of other protein substances: somatotropin (STH) and (ACTH). The aim of the study was to evaluate the effect of phosvitin on the permeation of ACTH and STH from semi-solid forms of the drug applied to the skin. Four hydrogel substrates were prepared using natural polymers: sodium alginate, methylcellulose, and starch. Based on the evaluation of physicochemical parameters, the hydrogel with the most favorable properties was selected and loaded with the active substances STH and ACTH, followed by the addition of phosvitin. A study of the permeation of STH and ACTH through the artificial cellulose membrane and through porcine skin was carried out without and with the addition of phosvitin. The effect of protein substances on rheological and textural parameters was studied. The evaluation of physicochemical parameters showed a favorable effect of STH and Phosvitin on the stability of the hydrogel with 4% methylcellulose and no effect of ACTH. All prepared formulations showed a reaction close to the natural pH of human skin. In the porcine skin permeation study, the addition of Phosvitin to the hydrogel with STH caused a slight increase in the amount of STH permeated and an increase in the time for STH to permeate porcine skin by 30 min. Phosvitin caused an increase in the amount of ACTH permeated through porcine skin almost twofold. Phosvitin may prove to be a promising permeation promoter for model protein-peptide substances when applied to the skin surface.

Immobilised artificial membrane liquid chromatography vs liposome electrokinetic capillary chromatography: Suitability in drug/bio membrane partitioning studies and effectiveness in the assessment of the passage of drugs through the respiratory mucosa.

This study pioneers a comparison of the application of biomimetic techniques, immobilised artificial membrane liquid chromatography (IAM LC) and liposome electrokinetic capillary chromatography (LEKC), for the prediction of pulmonary drug permeability. The pulmonary absorption profiles of 26 structurally unrelated drug-like molecules were evaluated using their IAM hydrophobicity index (CHI IAM) measured in IAM LC, and the logarithm of distribution constants (log KLEKC) derived from the LEKC experiments. Lipophilicity (phospholipids) parameters obtained from IAM LC and most LEKC analyses were linearly related to the n-octanol/water partitioning coefficients of the neutral forms (i.e., log Po/w values) to a moderate extent. However, the relationship with distribution coefficients at the experimental pH (7.4) (i.e., log D7.4) were weaker overall for IAM LC data and sigmoidal for some liposome compositions (phosphatidyl choline (PC): phosphatidyl inositol (PI) 85:15 mol% and 90:10 mol%) and concentrations (4 mM) in LEKC. This suggests that phospholipid partitioning supports both hydrophobic and electrostatic interactions occurring between ionised drugs and charged phospholipid moieties. The latter interactions are original when compared to those taking place in the more established n-octanol/water partitioning systems. A stronger correlation (R2 > 0.65) was identified between the LEKC retention parameters, and the experimental apparent lung permeability (i.e., log Papp values) as opposed to the values obtained by IAM LC. Therefore, LEKC offers unprecedented advantages over IAM LC in simulating cell membrane partitioning processes in the pulmonary delivery of drugs. Although LEKC has the advantage of more effectively simulating the electrostatic and hydrophobic forces in drug/pulmonary membrane interactions in vitro, the technique is unsuitable for analysing highly hydrophilic neutral or anionic compounds at the experimental pH. Conversely, IAM LC is useful for analysing compounds spanning a wider range of lipophilicity. Its simpler and more robust implementation, and propensity for high-throughput automation make it a favourable choice for researchers in drug development and pharmacological studies.

Recent developments in the application of immobilized artificial membrane (IAM) chromatography to drug discovery.

INTRODUCTION: Immobilized artificial membrane (IAM) chromatography is widely used in many aspects of drug discovery. It employs stationary phases, which contain phospholipids combining simulation of biological membranes with rapid measurements. AREAS COVERED: Advances in IAM stationary phases, chromatographic conditions and the underlying retention mechanism are discussed. The potential of IAM chromatography to model permeability and drug-membrane interactions as well as its use to estimate pharmacokinetic properties and toxicity endpoints including ecotoxicity, is outlined. Efforts to construct models for prediction IAM retention factors are presented. EXPERT OPINION: IAM chromatography, as a border case between partitioning and binding, has broadened its application from permeability studies to encompass processes involving tissue binding. Most IAM-based permeability models are hybrid models incorporating additional molecular descriptors, while for the estimation of pharmacokinetic properties and binding to off targets, IAM retention is combined with other biomimetic properties. However, for its integration into routine drug discovery protocols, reliable IAM prediction models implemented in relevant software should be developed, to enable its use in virtual screening and the design of new molecules. Conversely, preparation of new IAM columns with different phospholipids or mixed monomers offers enhanced flexibility and the potential to tailor the conditions according to the target property.

Partitioning of an Enzyme-Polymer Surfactant Nanocomplex into Lipid-Rich Cellular Compartments Drives In Situ Hydrolysis of Organophosphates.

Most organophosphates (OPs) are hydrophobic, and after exposure, can sequester into lipophilic regions within the body, such as adipose tissue, resulting in long term chronic effects. Consequently, there is an urgent need for therapeutic agents that can decontaminate OPs in these hydrophobic regions. Accordingly, an enzyme-polymer surfactant nanocomplex is designed and tested comprising chemically supercharged phosphotriesterase (Agrobacterium radiobacter; arPTE) electrostatically conjugated to amphiphilic polymer surfactant chains ([cat.arPTE][S-]). Experimentally-derived structural data are combined with molecular dynamics (MD) simulations to provide atomic level detail on conformational ensembles of the nanocomplex using dielectric constants relevant to aqueous and lipidic microenvironments. These show the formation of a compact admicelle pseudophase surfactant corona under aqueous conditions, which reconfigures to yield an extended conformation at a low dielectric constant, providing insight into the mechanism underpinning cell membrane binding. Significantly, it demonstrated that [cat.arPTE][S-] spontaneously binds to human mesenchymal stem cell membranes (hMSCs), resulting in on-cell OP hydrolysis. Moreover, the nanoconstruct can endocytose and partition into the intracellular fatty vacuoles of adipocytes and hydrolyze sequestered OP.

Determination of bisphosphonate properties in terms of bioavailability, bone affinity, and cytotoxicity.

BACKGROUND: The study aimed to evaluate the therapeutic potential of fourteen newly synthesized bisphosphonates by assessing their bioavailability, bone affinity, and cytotoxicity. These bisphosphonates included a series of aminomethylenebisphosphonates and standard compounds such as risedronate and tiludronate. METHODS: Drug permeability was determined using Parallel Artificial Membrane Permeability Assays (PAMPA), while bone affinity was assessed by sorption on hydroxyapatite. Bacterial cell response to the bisphosphonates was also examined using Lactobacillus paracasei cells as a model. RESULTS: Several tested compounds, including BP3 to BP8 and BP11, which feature substituents in the pyridine ring such as methyl groups, iodine, bromine, chlorine, or hydroxyl groups, demonstrated potentially more beneficial therapeutic properties than commercially used bisphosphonates. These compounds showed stronger bone affinity and higher gastrointestinal absorption with comparable or lower cytotoxic effects. Specifically, BP11 exhibited the highest bone affinity, while BP8 and BP11 showed the greatest permeability. CONCLUSIONS: The findings suggest that BP3 BP8, and BP11 are promising candidates for further research. These results highlight the importance of comprehensively evaluating bisphosphonates' therapeutic properties to identify effective treatments for osteoporosis and other bone diseases.

Construction of Discrimination Models of Cationic Drugs for Phospholipidosis Induction Potential by Using Interaction Data with Immobilized Artificial Membrane as Well as Physicochemical Properties.

Accurate prediction of the phospholipidosis-induction risk of drugs at early stages is important in drug development. So far, discrimination models for predicting the induction risk of cationic drugs have been proposed, but it is still challenging to accurately predict the risk of cationic drugs with intermediate hydrophobicity (logP). In this study, we introduced a parameter (Δlogk40) reflecting not only hydrophobic interaction but also interactions with the polar headgroup between cationic drugs and phospholipids, obtained with liquid chromatography using an immobilized artificial membrane column. The parameter was used along with other physicochemical properties as features to construct discrimination models. Linear discriminant analysis, the modified Mahalanobis discriminant analysis, support vector machine, and random forest were employed for model construction. The results showed that all discrimination models exhibited good predictive performance, with the modified Mahalanobis discriminant analysis and random forest providing the best results for cationic drugs, suggesting that the usefulness of the parameter reflecting complex interactions between cationic drugs and immobilized artificial membrane for constructing discrimination models to predict the induction risk. Furthermore, by applying the parameter as a feature in constructing discrimination models, we demonstrated an improvement in the predictive performance for drugs with intermediate hydrophobicity.

ATP regeneration by ATPases for in vitro biotransformation.

Adenosine triphosphate (ATP) regeneration is a significant step in both living cells and in vitro biotransformation (ivBT). Rotary motor ATP synthases (ATPases), which regenerate ATP in living cells, have been widely assembled in biomimetic structures for in vitro ATP synthesis. In this review, we present a comprehensive overview of ATPases, including the working principle, orientation and distribution density properties of ATPases, as well as the assembly strategies and applications of ATPase-based ATP regeneration modules. The original sources of ATPases for in vitro ATP regeneration include chromatophores, chloroplasts, mitochondria, and inverted Escherichia coli (E. coli) vesicles, which are readily accessible but unstable. Although significant advances have been made in the assembly methods for ATPase-artificial membranes in recent decades, it remains challenging to replicate the high density and orientation of ATPases observed in vivo using in vitro assembly methods. The use of bioproton pumps or chemicals for constructing proton motive forces (PMF) enables the versatility and potential of ATPase-based ATP regeneration modules. Additionally, overall robustness can be achieved via membrane component selection, such as polymers offering great mechanical stability, or by constructing a solid supporting matrix through layer-by-layer assembly techniques. Finally, the prospects of ATPase-based ATP regeneration modules can be expected with the technological development of ATPases and artificial membranes.

Differential susceptibility of geographically distinct Ixodes ricinus populations to tick-borne encephalitis virus and louping ill virus.

Tick-borne encephalitis virus (TBEV) is an emerging pathogen in the Netherlands. Multiple divergent viral strains are circulating and the focal distribution of TBEV remains poorly understood. This may, however, be explained by differences in the susceptibility of tick populations for specific viruses and viral strains, and by viral strains having higher infection success in their local tick population. We investigated this hypothesis by exposing Dutch Ixodes ricinus ticks to two different TBEV strains: TBEV-NL from the Netherlands and TBEV-Neudoerfl from Austria. In addition, we exposed ticks to louping Ill virus (LIV), which is endemic to large parts of the United Kingdom and Ireland, but has not been reported in the Netherlands. Ticks were collected from two locations in the Netherlands: one location without evidence of TBEV circulation and one location endemic for the TBEV-NL strain. Ticks were infected in a biosafety level 3 laboratory using an artificial membrane feeding system. Ticks collected from the region without evidence of TBEV circulation had lower infection rates for TBEV-NL as compared to TBEV-Neudoerfl. Vice versa, ticks collected from the TBEV-NL endemic region had higher infection rates for TBEV-NL compared to TBEV-Neudoerfl. In addition, LIV infection rates were much lower in Dutch ticks compared to TBEV, which may explain why LIV is not present in the Netherlands. Our findings show that ticks from two distinct geographical populations differ in their susceptibility to TBEV strains, which could be the result of differences in the genetic background of the tick populations.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

PURPOSE: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. METHODS: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. RESULTS: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. CONCLUSION: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.

Lithocholic acid-based oligomers as drug delivery candidates targeting model of lipid raft.

This study presents a new approach to designing a lithocholic acid functionalized oligomer (OLithocholicAA-X) that can be used as a drug carrier with additional, beneficial activity. Namely, this novel oligomer can incorporate an anti-cancer drug due to the application of an effective backbone as its component (lithocholic acid) alone is known to have anticancer activity. The oligomer was synthesized and characterized in detail by nuclear magnetic resonance, attenuated total reflectance Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, thermal analysis, and mass spectrometry analysis. We selected lipid rafts as potential drug carrier-membrane binding sites. In this respect, we investigated the effects of OLithocholicAA-X on model lipid raft of normal and altered composition, containing an increased amount of cholesterol (Chol) or sphingomyelin (SM), using Langmuir monolayers and liposomes. The surface topography of the studied monolayers was additionally investigated by atomic force microscopy (AFM). The obtained results showed that the investigated oligomer has affinity for a system that mimics a normal lipid raft (SM:Chol 2:1). On the other hand, for systems with an excess of SM or Chol, thermodynamically unfavorable fluidization of the films occurs. Moreover, AFM topographies showed that the amount of SM determines the bioavailability of the oligomer, causing fragmentation of its lattice.

Systematic literature review of in vivo rat femoral defect models using biomaterials to improve the induced membrane technique: a comprehensive analysis.

Purpose: The aim of this study was to conduct a systematic literature review analyzing the results of in vivo rat femoral defect models using biomaterials for improving the induced membrane technique (IMT). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Embase, and Web of Science databases were searched. Inclusion criteria were studies reporting results of the IMT in in vivo rat femoral critical-sized defect models using a biomaterial possibly combined with molecules. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments guidelines. Results: Twenty studies met the inclusion criteria. Femoral stabilization with plate and screws was the most frequent. Histologic, biomechanical, and/or radiologic analyses were performed. In two-stage strategies, the PMMA spacer could be associated with bioactive molecules to enhance IM growth factor expression and improve bone formation. Modulating the roughness of spacers could increase IM thickness and accelerate its formation. In one-stage strategies, human tissue-derived membranes combined with bone grafting achieved bone formation comparable to a standard IMT. All calcium phosphate grafts seemed to require a functionalization with growth factors or bone marrow mononuclear cells to improve outcomes compared with non-functionalized grafts. Conclusion: This systematic review described the main parameters of the in vivo rat femoral defect models using biomaterials to improve the induced membrane technique. Although the studies included had several methodological limitations that may limit the scope of these conclusions, one- and two-stage strategies reported promising results with biomaterials to improve the IMT.

Modeling of small molecule's affinity to phospholipids using IAM-HPLC and QSRR approach enhanced by similarity-based machine algorithms.

Immobilized artificial membrane chromatography (IAM) has been proposed as a more biosimilar alternative to classical lipophilicity measurement. Determination of small molecule's affinity to phospholipids can be supported for predicting their behavior in the human body. Therefore, a better understanding of the molecular interaction mechanism between small xenobiotics and phospholipids can accelerate drug discovery. Here, the quantitative structure-retention relationships (QSRR) approach was integrated with mechanistic descriptors calculated using Chemicalize software to propose an easy-to-interpretation QSRR model. Considering the heterogeneous character of the data set, locally weighted least squares kernel regression belonging to similarity-based machine learning methods have been applied. The results showed that lipophilicity, charge, and maximum projection area determine molecule binding to phospholipids. Full validation of the obtained model based on OECD recommendations has been performed and the applicability domain was defined using the probability-oriented distance-based approach. The high values of predictive squared correlation coefficient (Q2), and small root mean square error of prediction (RMSEP), 0.812 and 6.739, respectively, confirmed that the obtained QSRR model is not well-fitted to the training data but also showed prediction power. Additionally, only 1.5% of molecules from the training set and 2.8% from the validation test are outside the applicability domain, confirming great predictive abilities.

Development and validation of PAMPA-BBB QSAR model to predict brain penetration potential of novel drug candidates.

Efficiently circumventing the blood-brain barrier (BBB) poses a major hurdle in the development of drugs that target the central nervous system. Although there are several methods to determine BBB permeability of small molecules, the Parallel Artificial Membrane Permeability Assay (PAMPA) is one of the most common assays in drug discovery due to its robust and high-throughput nature. Drug discovery is a long and costly venture, thus, any advances to streamline this process are beneficial. In this study, ∼2,000 compounds from over 60 NCATS projects were screened in the PAMPA-BBB assay to develop a quantitative structure-activity relationship model to predict BBB permeability of small molecules. After analyzing both state-of-the-art and latest machine learning methods, we found that random forest based on RDKit descriptors as additional features provided the best training balanced accuracy (0.70 ± 0.015) and a message-passing variant of graph convolutional neural network that uses RDKit descriptors provided the highest balanced accuracy (0.72) on a prospective validation set. Finally, we correlated in vitro PAMPA-BBB data with in vivo brain permeation data in rodents to observe a categorical correlation of 77%, suggesting that models developed using data from PAMPA-BBB can forecast in vivo brain permeability. Given that majority of prior research has relied on in vitro or in vivo data for assessing BBB permeability, our model, developed using the largest PAMPA-BBB dataset to date, offers an orthogonal means to estimate BBB permeability of small molecules. We deposited a subset of our data into PubChem bioassay database (AID: 1845228) and deployed the best performing model on the NCATS Open Data ADME portal (https://opendata.ncats.nih.gov/adme/). These initiatives were undertaken with the aim of providing valuable resources for the drug discovery community.

Impact of miconazole nitrate ferrying cationic and anionic nanoemulsion and gels on permeation profiles of across EpiDerm, artificial membrane, and skin: Instrumental evidences.

Based on our previous report, the study was extended to investigate the impact of miconazole nitrate (MCN) loaded cationic/anionic nanoemulsions and nanoemulsion gels on permeation behaviour across artificial-membrane, EpiDerm, and rat skin. Nanoemulsions and gels were evaluated for size, charge, viscosity, size-distribution, pH, and percent entrapment efficiency (%EE). In vitro drug diffusion across artificial membrane and EpiDerm were conducted to get diffusion coefficients. Permeation profiles were studied using rat skin to investigate mechanistic insight of formulated mediated permeation followed by CLSM (confocal laser scanning microscopy), SEM (scanning electron microscopy), AFM (atomic force microscopy), and irritation studies. Results showed that MCNE11-Rh (probed cationic nanoemulsion at pH âˆ¼ 7.2) and MNE11-Rh (probed anionic nanoemulsion at pH âˆ¼ 7.2) showed size values of 158 nm and 145 nm, respectively whereas MCNE11-GR (probed cationic nanoemulsion gel at pH âˆ¼ 6.8) and MNE11-GR (probed anionic nanoemulsion gel at pH âˆ¼ 6.8) exhibited size values 257 nm and 243 nm, respectively. The %EE values were found to be as 91.5 % and 89.6 % for MCNE11-Rh and MNE11-Rh, respectively. The gels (∼6000 cP) elicited relatively high viscosity than nanoemulsions (∼3300 - 3500 cP). MCNE11-GR showed the highest values of permeation flux, diffusion rate, diffusion coefficient (D), and permeation coefficient (P) across artificial membrane, EpiDerm, and rat skin which may be attributed to three potential factors (cationic charge, composition, and hydration by the hydrophilic gel) working in tandem. Transepidermal water loss (TEWL) by the MCNE11-GR was maximum (14.4 g/m2h) than control (6.1 g/m2h) indicating augmented interaction of MCNE11-Rh with skin components. Conclusively, cationic nanoemulsion gel was promising carrier for enhanced permeation and the drug access to the dermal region to treat deep seated fungal infections.

Development and Prospective Applications of 3D Membranes as a Sensor for Monitoring and Inducing Tissue Regeneration.

For decades, tissue regeneration has been a challenging issue in scientific modeling and human practices. Although many conventional therapies are already used to treat burns, muscle injuries, bone defects, and hair follicle injuries, there remains an urgent need for better healing effects in skin, bone, and other unique tissues. Recent advances in three-dimensional (3D) printing and real-time monitoring technologies have enabled the creation of tissue-like membranes and the provision of an appropriate microenvironment. Using tissue engineering methods incorporating 3D printing technologies and biomaterials for the extracellular matrix (ECM) containing scaffolds can be used to construct a precisely distributed artificial membrane. Moreover, advances in smart sensors have facilitated the development of tissue regeneration. Various smart sensors may monitor the recovery of the wound process in different aspects, and some may spontaneously give feedback to the wound sites by releasing biological factors. The combination of the detection of smart sensors and individualized membrane design in the healing process shows enormous potential for wound dressings. Here, we provide an overview of the advantages of 3D printing and conventional therapies in tissue engineering. We also shed light on different types of 3D printing technology, biomaterials, and sensors to describe effective methods for use in skin and other tissue regeneration, highlighting their strengths and limitations. Finally, we highlight the value of 3D bioengineered membranes in various fields, including the modeling of disease, organ-on-a-chip, and drug development.

Potential of liposomes and lipid membranes for the separation of ß-blockers by capillary electromigration and liquid chromatographic techniques.

ß-Blockers belong to a frequently used class of drugs primarily used to treat heart and circulatory conditions. Here we describe the use of lipid vesicles and liposomes as cell membrane biomimicking models in capillary electromigration (CE) and liquid chromatography (LC) techniques for the investigation of interactions between lipid membranes and ß-blockers. In addition to liposomes, the use of commercial intravenous lipid emulsions, and their interactions with ß-blockers are also discussed. Different CE and LC instrumental techniques designed for these purposes are introduced. Other methodologies for studying interactions between ß-blockers and lipid membranes are also briefly discussed, and the different methodologies are compared. The aim is to give the reader a good overview on the status of the use of liposomes and lipids in CE and LC for studying ß-blocker interactions.

Do it yourself: fabricating and evaluating a mosquito (Diptera: Culicidae) blood-feeding device to replace a commercial option.

Tools for rearing hematophagous insects, such as mosquitoes (Diptera: Culicidae), in an insectary are essential for research and operational evaluations in vector biology and control. There is an abundance of low-cost options for practitioners without conventional infrastructure. However, few midrange options exist that provide a balance of efficiency and low material waste. We present here a reproducible design for an electrically powered blood-feeding device that offers long-term reusability, low material waste, and customizability for different species or experiments. The limitation is the requirement for electricity, but the gain is a simple, low-skill device that can be modified as needed. To validate the design, assessments of feeding angle and blood-feeding success were compared between the Salt Lake City Mosquito Abatement District artificial membrane feeder (SLAM) and a commercial system (Hemotek). Engorgement in Aedes aegypti (80-90%), Culex pipiens (50-80%), and Culex tarsalis (30-75%) was similar between the 2 units, resulting in nearly identical fecundity outcomes between devices. Additionally, 45° angles were more successful, generally, than presenting the feeders flat or vertical to the mosquitoes (df3,48, P = 1.014 × 10-15). This angle is simple to present with the SLAM device. Materials for in-house reproduction of the SLAM system are now widely available in regions with access to e-commerce and shipped goods. This results in a device schematic that should fit well into a relatively modular, do-it-yourself paradigm where the practitioner needs only to assemble some materials without complex engineering. This article provides schematics, cost comparison, and validation of the in-house-made SLAM system.

Development and evaluation of niacinamide transdermal formulation by artificial membrane permeability.

Despite many efforts to improve the transdermal permeability of drugs, most of them are blocked by the skin barrier. Niacinamide (NAC) is a Biopharmaceutics Classification System class I drug with high aqueous solubility and intestinal permeability. Due to the high solubility and intestinal permeability of NAC, the development of new formulations is insufficient as transdermal, injection etc. Thus, this study aimed to develop the novel NAC formulation with improved skin permeability and secured stability. The NAC formulation approach is to first select a solvent that improves skin permeability, and then select a second penetration enhancer to determine the final formulation. All formulations were evaluated for skin permeability using an artificial membrane (Strat-M®). The optimal formulation (non-ionic formulations (NF1) consisted of NAC/Tween®80 = 1:1 wt ratio in dipropylene glycol [DPG]) showed the highest permeability in all formulations in PBS buffer (pH 7.4). The thermal properties of NF1 were altered. Moreover, NF1 maintained a stable drug content, appearance, and pH value for 12 months. In conclusion, DPG had an excellent effect in increasing the NAC permeation, and Tween®80 played a boosting role. Through this study, an innovative NAC formulation was developed, and good results are expected for human transdermal research.

Nondestructive Methods of Pathogen Detection: Importance of Mosquito Integrity in Studies of Disease Transmission and Control.

Mosquitoes are vectors of many pathogens, including viruses, protozoans, and helminths, spreading these pathogens to humans as well as to wild and domestic animals. As the identification of species and the biological characterization of mosquito vectors are cornerstones for understanding patterns of disease transmission, and the design of control strategies, we conducted a literature review on the current use of noninvasive and nondestructive techniques for pathogen detection in mosquitoes, highlighting the importance of their taxonomic status and systematics, and some gaps in the knowledge of their vectorial capacity. Here, we summarized the alternative techniques for pathogen detection in mosquitoes based on both laboratory and field studies. Parasite infection and dissemination by mosquitoes can also be obtained via analyses of saliva- and excreta-based techniques or of the whole mosquito body, using a near-infrared spectrometry (NIRS) approach. Further research should be encouraged to seek strategies for detecting target pathogens while preserving mosquito morphology, especially in biodiversity hotspot regions, thus enabling the discovery of cryptic or new species, and the determination of more accurate taxonomic, parasitological, and epidemiological patterns.

In vitro-in vivo relationship for amorphous solid dispersions using a double membrane dissolution-permeation setup.

The use of amorphous solid dispersions (ASDs) is one commonly applied formulation strategy to improve the oral bioavailability of poorly water-soluble drugs by overcoming dissolution rate and/or solubility limitations. While bioavailability enhancement of ASDs is well documented, it has often been a challenge to establish a predictive model describing in vitro-in vivo relationship (IVIVR). In this study, it is hypothesized that drug absorption might be overestimated by in vitro dissolution-permeation (D/P)-setups, when drug in suspension has the possibility of directly interacting with the permeation barrier. This is supported by the overprediction of drug absorption from neat crystalline efavirenz compared to four ASDs in a D/P-setup based on the parallel artificial membrane permeability assay (PAMPA). However, linear IVIVR (R2 = 0.97) is established in a modified D/P-setup in which the addition of a hydrophilic PVDF-filter acts as a physical boundary between the donor compartment and the PAMPA-membrane. Based on microscopic visualization, the improved predictability of the modified D/P-setup is due to the avoidance of direct dissolution of drug particles in the lipid components of the PAMPA-membrane. In general, this principle might aid in providing a more reliable evaluation of formulations of poorly water-soluble drugs before initiating animal models.