Lipophilic Research Articles

Promises of Lipid-Based Nanocarriers for Delivery of Dimethyl Fumarate to Multiple Sclerosis Brain.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the central nervous system (CNS) infecting 2.5million people worldwide. It is the most common nontraumatic neurological impairment in young adults. The blood-brain barrier rupture for multiple sclerosis pathogenesis has two effects: first, during the onset of the immunological attack, and second, for the CNS self-sustained "inside-out" demyelination and neurodegeneration processes. In addition to genetic variations, environmental and lifestyle variables can also significantly increase the risk of developing MS. Dimethyl fumarate (DMF) and sphingosine-1-phosphate (S1P) receptor modulators that may pass the blood-brain barrier and have positive direct effects in the CNS with quite diverse mechanisms of action raise the possibility that a combination therapy could be successful in treating MS. Lipid nanocarriers are recognized as one of the best drug delivery techniques to the brain for effective brain delivery. Numerous scientific studies have shown that lipid nanoparticles can enhance the lipid solubility, oral bioavailability, and brain availability of the drugs. Nanolipidic carriers for DMF delivery could be derived through vitamin D, tocopherol acetate, stearic acid, quercetin, cell-mimicking platelet-based, and chitosan-alginate core-shell-corona-shaped nanoparticles. Clinical and laboratory diagnosis of MS can be performed mainly through magnetic resonance imaging. The advancements in nanotechnology have enabled the clinicians to cross the blood-brain barrier and to target the brain and central nervous system of the patient with multiple sclerosis.

A Combination of Magnoflorine and Spinosin Improves the Antidepressant effects on CUMS Mouse Model.

Depression is a common neuropsychiatric disease. As a famous traditional Chinese medicine with significant anti-depressive and sleep-promoting effects, Ziziphi Spinosae Semen (ZSS) has attracted the attention of many researchers. Although it is well known that Magnoflorine (MAG) and Spinosin (SPI) were the main active components isolated from ZSS, there is a lack of research on the combined treatment of depression with these two ingredients. The shaking bottle method was used to simulate the human environment for detecting the changes in oil-water partition coefficient before and after the drug combination. Cell viability was evaluated by the MTT assay. To establish a mouse model of depression and insomnia by CUMS method, and then to explore the effect of combined administration of MAG and SPI on depression in CUMS model by observing behavior and analyzing pharmacokinetics. The change in LogP values affected the lipid solubility of MAG and increased the water solubility of SPI, allowing them to penetrate more easily through the blood-brain barrier into the brain. Compared with the model group, MAG-SPI with a concentration of 60 μM significantly increased cell survival rate. In both the TST and FST experiments, the mice showed a decrease in immobilization time. Pharmacokinetic results showed that the pharmacokinetic parameters, Cmax and AUC of MAG and SPI, were increased in the case of combination, which resulted in enhancement of their relative bioavailability and improvement of in vivo effects. The present study demonstrated that a combination of MAG and SPI had a synergistic antidepressant effect in CUMS mouse model.

Fenthion flea-killer: Unpredictable and dangerous

Introduction This case of fenthion poisoning demonstrates the delayed, protracted and yet unpredictable nature of cholinergic effects which are unique to fenthion toxicity. Case Presentation A 36-year-old female presented to the emergency department with drowsiness and vomiting, 8 hours after an unknown pesticide ingestion. She had some cholinergic symptoms (miosis, incontinence, emesis) suspicious of organophosphate toxicity but was initially well with no bronchorrhea or bradycardia. During her admission, she developed increasing salivation and bronchorrhea resulting in respiratory failure requiring intubation 27 h’ post-ingestion. Possible aspiration pneumonitis was initially considered given the delayed nature of deterioration. However, blood toxicology results confirmed fenthion poisoning. Atropine and pralidoxime boluses were administered followed by continuous infusion. She was extubated after initial improvement and stabilization – only to require reintubation for recurring respiratory failure and seizures on Days 4 and 5, each time following apparent recovery. She was eventually weaned off mechanical ventilation only on Day 31. Discussion and Conclusion This case illustrates the importance of physician awareness to potentially innocuous presentations of fenthion poisoning as symptoms at the onset may appear benign and falsely reassuring. Serious toxic manifestations may be significantly delayed over a prolonged, waxing-and-waning clinical course because of the compound’s high lipid solubility and metabolism into potent secondary compounds.

Bioinformatics-based Analyses and B/Th Cell Epitope Prediction of Mugwort Pollen Allergen Art v 1 Protein.

To analyze the sequence characteristics of mugwort pollen allergen Art v 1 protein and predict its B cell and Th (helper T cell) cell epitopes, the gene sequence and amino acid sequence of Art v 1 protein were obtained by referring to Genebank. ExPASy's Prot Param, TMHMM, DNAstar Protean, Swiss-Model, UCLA-DOE LAB SAVES v6.0, and IEDB were used to analyze and predict physicochemical properties, transmembrane region, secondary structure, tertiary structure, and B cell and Th cell epitopes of the protein. The Art v 1 protein is composed of 132 amino acid residues, the relative molecular weight is 13404.26, the molecular formula is C584H903N157O181S12, pI value is 7.49, the lipid solubility index is 41.59, and the hydrophilic index is -0.454, which is considered as hydrophilic protein. The instability index (ii) is 78.11, which is classified as an unstable protein. The N-terminus of the protein has an α-helical transmembrane region, which is located in the 5-27 amino acid residue sequence, and the 1-24 position is the signal peptide sequence. There are random coil, β-turn, α-helix, and β-sheet, and it also contains hydrophilic region, flexible region, and surface accessibility region structures. The prediction results of tertiary structure are consistent with the analysis results of secondary structure. Five dominant B cell epitopes were predicted, which were Art v 1 71-87, Art v 1 33-49, Art v 1 104-120, Art v 1 95-111, and Art v 1 86-102. There were five Th cell dominant epitopes, which were Art v 1 2-16, Art v 1 3-17, Art v 1 4-18, Art v 1 5-19, and Art v 1 6-20. The Art v 1 protein is predicted to have good antigenicity due to the presence of B cell and Th cell epitopes.

Dynamic Transport and Distribution of Organic Pollutants in Water and Sediments of the Rur River

The distribution and fate of organic pollutants within different compartments of a river system are determined by several key effects and drivers. Within the scope of this study, the aqueous and sedimentary compartments have been analyzed complementary to understand transport and accumulation pathways and to determine temporospatial effects. The bi-annual campaigns allow general statements to be made about relevant processes and effects on pollutant distribution. GC/MS non-target screenings revealed that there is only a minor group of contaminants that occur both in the water and in the riverbed. Nevertheless, for both phases, the main contamination with organic compounds occurred in the anthropogenic, middle to lower course of the river with loads up to 18.3 kg/d (2,4,7,9-tetramethyl-5-decyne-4,7-diol, TMDD) in the water and amounts up to 3.3 mg/gTOC (ƩEPA16 polycyclic aromatic hydrocarbons, PAHs) in the riverbed. Main emission sources were comparable, resulting in a high, almost constant contamination level which also contributes to the pollution of the superior, receiving river. Indeed, the pollution transport of the aqueous and sedimentary phases was closely connected, but with slight temporal and spatial heterogeneities. For the aqueous compartment, seasonal effects were identified while a remarkable change in riverbed contamination occurred due to an extreme flood event. However, dams within the catchment system cause a disconnection of the transport of lipophilic and hydrophilic substances. Overall, the combined investigation of different phases is an important aspect for a comprehensive view of river and environmental contamination.

A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities.

Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid-protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

Druggable genomic landscapes of high-grade gliomas.

Despite the putatively targetable genomic landscape of high-grade gliomas, the long-term survival benefit of genomically-tailored targeted therapies remains discouraging. Using glioblastoma (GBM) as a representative example of high-grade gliomas, we evaluated the clonal architecture and distribution of hotspot mutations in 388 GBMs from the Cancer Genome Atlas (TCGA). Mutations were matched with 54 targeted therapies, followed by a comprehensive evaluation of drug biochemical properties in reference to the drug's clinical efficacy in high-grade gliomas. We then assessed clinical outcomes of a cohort of patients with high-grade gliomas with targetable mutations reviewed at the Johns Hopkins Molecular Tumor Board (JH MTB; n = 50). Among 1,156 sequence alterations evaluated, 28.6% represented hotspots. While the frequency of hotspot mutations in GBM was comparable to cancer types with actionable hotspot alterations, GBMs harbored a higher fraction of subclonal mutations that affected hotspots (7.0%), compared to breast cancer (4.9%), lung cancer (4.4%), and melanoma (1.4%). In investigating the biochemical features of targeted therapies paired with recurring alterations, we identified a trend toward higher lipid solubility and lower IC50 in GBM cell lines among drugs with clinical efficacy. The drugs' half-life, molecular weight, surface area and binding to efflux transporters were not associated with clinical efficacy. Among the JH MTB cohort of patients with IDH1 wild-type high-grade gliomas who received targeted therapies, trametinib monotherapy or in combination with dabrafenib conferred radiographic partial response in 75% of patients harboring BRAF or NF1 actionable mutations. Cabozantinib conferred radiographic partial response in two patients harboring a MET and a PDGFRA/KDR amplification. Patients with IDH1 wild-type gliomas that harbored actionable alterations who received genotype-matched targeted therapy had longer progression-free (PFS) and overall survival (OS; 7.37 and 14.72 respectively) than patients whose actionable alterations were not targeted (2.83 and 4.2 months respectively). While multiple host, tumor and drug-related features may limit the delivery and efficacy of targeted therapies for patients with high-grade gliomas, genotype-matched targeted therapies confer favorable clinical outcomes. Further studies are needed to generate more data on the impact of biochemical features of targeted therapies on their clinical efficacy for high-grade gliomas.

The Lipid Solubility of Most Drugs Play Important Role of Its Pharmacological Action and Duration of Action

The fact of human body and animal body formed of organs which formed of tissue which its constituents are the cells. The cell enveloped by cell membrane which contain more its content of lipid compounds to protect the cell. Hence when the chemical compounds (drugs) across to the cytoplasm of the cell must have a lipophilic character. Also there is a fact the oily substances not mix with the watery substance, so must be take a cream form (water in oil or oil in water emulsion), so the drugs must be soluble in lipid to across the cell to obtain the desirable effect. The partition co-efficient is a significant expression of lipid solubility. Many of drugs convert to prodrug this prodrug has highly lipid solubility and has long duration of action e.g., testosterone cypionate, rolitetracycline, penicillin procaine, benzylpenicillin G, nandrolone decanoate….etc., on the other hand the water soluble compounds (hydrophilic drugs) e.g., vitamin B complexes which exert its effects and excreted from the kidney quickly this indicate to no long duration of vitamin B complex except the cyanocobalamin (vit.B12) which incorporated to sesame oil to deposit in the body to treatment the inflammation of nerves of diabetic patients which suffering from neuropathy.

Abstract C041: Drug repurposing to target TGF-β in chemoresistant high-grade serous ovarian cancer

Abstract High-grade serous ovarian cancer (HGSOC) has low 5-year survival rate of 48%, due to chemotherapy resistance. Effective new therapies are required to improve the survival rate of HGSOC. TGF-β is a family of proteins associated with epithelial-mesenchymal transition and have been implicated in ovarian cancer progression and chemoresistance. Drugs that target TGF-β may have potential to be used to treat chemoresistant HGSOC and control tumour growth and progression. Drug repurposing is a strategy to identify new uses for approved drugs outside of their original indication, and ensure timely access to efficacious and cost-effective therapy for chemoresistant HGSOC. The aims of the study is to determine the effect of the repurposed drug teniposide on HGSOC cell growth, death, and apoptosis. A ligand-based screening was performed by Cresset Discovery for approved drugs that bind to the TGF-β receptor complex and ligand. Teniposide was shortlisted according to its dosing, lipid solubility, pharmacokinetics, and side effects. MTT assays were performed on eight molecularly-characterised HGSOC cell lines to obtain the IC50 of teniposide. The effect of the IC50 dose of teniposide on HGSOC cell growth, death, and apoptosis were monitored on the IncuCyte live-cell imager. Western blotting was performed to determine the expression of TGF-β signalling pathway proteins after treatment with teniposide. The average IC50 of teniposide in HGSOC cell lines is 10µM, within the range of the maximum plasma concentration (61µM). HGSOC cell lines treated with 10µM teniposide showed decreased cell growth, and increased cell death and apoptosis, similar to HGSOC cell lines treated with clinically-relevant dose of carboplatin (30µM). HGSOC cell lines treated with 10µM teniposide showed significantly higher cell death and apoptosis compared to treatment with 30µM carboplatin. Our preliminary results show that teniposide significantly reduced proliferation of HGSOC and has potential to be repurposed for treatment of chemoresistant HGSOC. Citation Format: Michelle WY Wong-Brown, Zlata Johnson, Saad Salem, Bayley G Matthews, Caroline E Ford, Deborah J Marsh, Nikola A Bowden. Drug repurposing to target TGF-β in chemoresistant high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C041.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of Panax ginseng, possessing complement inhibition ability, structural similarity to cholesterol, and comparable fat solubility to phospholipids, were used as promising candidate IIS inhibitors. Two different types of ginsenoside-based lp-NDs (Gs lp-NDs) were created, and their efficacy in reducing IIS recognition was examined. The Gs lp-NDs were observed to inhibit the adsorption of C3 in the protein corona (PC) and the generation of SC5b-9. Adding Gs to lp-NDs reduced complement adsorption and phagocytosis, resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs. These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants, potentially reducing non-specific clearance by the IIS and improving lifespan.

A review on recent advances on nobiletin in central and peripheral nervous system diseases

In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system.

The Biology, Pathological Roles of Exosomes and Their Clinical Application in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease with a high global incidence and places a great burden on the patient, their family and society. Early diagnosis of PD is the key to hindering the progression process and may enable treatment to partially reverse the disease course. Exosomes are lipid bilayers with a diameter of 40-160nm (average ∼100nm), show a cup-shaped structure in transmission electron microscopy (TEM) images, and contain different types of nucleic acids and proteins. On the one hand, several molecules contained in exosomes are correlated with PD pathology. On the other hand, biomarkers based on exosomes have gradually become diagnostic tools in PD. Since exosomes can freely cross the blood-brain barrier, CNS-derived exosomes obtained from the periphery have the potential to be a powerful marker for early PD diagnosis. Of course, exosomes also have great potential as drug delivery systems due to their low toxicity, lipid solubility and immunological inertness. However, there is still a lack of standardized, efficient, and ultrasensitive methods for the isolation of exosomes, hindering the development of effective biomarkers. Therefore, this review describes the biological characteristics of exosomes, exosome extraction methods, and the pathological role, diagnostic/therapeutic value of exosomes in PD.

Advances in the Preparation, Stability, Metabolism, and Physiological Roles of Anthocyanins: A Review.

Anthocyanins are natural flavonoid polyphenolic compounds widely found in fruits and vegetables. They exhibit antioxidant properties and prophylactic effects in the immune and cardiovascular systems, confer protection against cancer, and contribute to the prevention of cardiovascular diseases. Thus, their incorporation into functional foods, pharmaceuticals, supplements, and cosmetic formulations aims at promoting human well-being. This review comprehensively outlined the structural attributes of anthocyanins, expanding upon diverse methodologies employed for their extraction and production. Additionally, the stability, metabolic pathways, and manifold physiological functions of anthocyanins were discussed. However, their constrained fat solubility, susceptibility to instability, and restricted bioavailability collectively curtail their applicability and therapeutic efficacy. Consequently, a multidimensional approach was imperative, necessitating the exploration of innovative pathways to surmount these limitations, thereby amplifying the utilitarian significance of anthocyanins and furnishing pivotal support for their continual advancement and broader application.

Effect of hesperidin on deltamethrin toxicity in rat periodontal membrane

Aim: Deltamethrin (DM), a hydrophobic and lipophilic substance used for insect control, easily accumulates in the body, increasing ROS production and causing mucosal inflammation and damage. The aim of this study was to explore the prophylactic effects of hesperidin on DM toxicity in periodontal membrane. Methods: The study was conducted for 14 days on 21 male Wistar albino rats. The experimental animals were divided into three groups (n=7): The Sham group received 0.9% NaCl (1 mL). The deltamethrin group received 0.5 mg/kg DM (1 mL, dissolved in dimethyl sulfoxide). The deltamethrin + hesperidin group received DM (0.5 mg/kg) + hesperidin (100 mg/kg) (both drugs dissolved in 1 mL dimethyl sulfoxide). All treatments were administered daily via the orogastric route for 14 days. At the end of the experiment, the rats were euthanized by cervical dislocation, and biochemical and histological analyses were performed. Results: The biochemical tests showed significantly higher malondialdehyde (MDA) levels in the deltamethrin group than in the Sham group. Combined application of hesperidin and deltamethrin resulted in significantly lower MDA levels in the deltamethrin + hesperidin group than in the deltamethrin group. Histopathological examination of the periodontal tissues of the deltamethrin group revealed cell degeneration at the alveolar bone-tooth junction, including atypical cells, irregularity in collagen fibers, dilatation and congestion of the blood vessels, and inflammatory cell infiltrates distributed in aggregate and solitary forms. The deltamethrin + hesperidin group showed substantially less cell degeneration. Conclusion: Hesperidin application helped alleviate deltamethrin toxicity by preventing oxidative stress and reducing cell degeneration. How to cite this article: İpek F, Deveci E, İpek P. Effect of hesperidin on deltamethrin toxicity in rat periodontal membrane. J Med Dent Invest 2023;4:e230332. https://doi.org/10.5577/jomdi.e230332 Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

Lipid recovery from deep eutectic solvents by polar antisolvents

Deep eutectic solvents (DES) can be a green alternative extraction technology for microalgae lipids, acting simultaneously as a pre-treatment agent and solvent. However, due to the low vapor pressure of both DES and lipid solute, the recovery of lipids and solvent regeneration remains difficult. In this study, we developed a novel strategy to separate the dissolved sunflower and model algae oil from imidazole/hexanoic acid DES by using polar antisolvents (water, methanol, and ethanol). The polarity and the amount of antisolvent influenced the lipid solubility in DES. While the water was the strongest antisolvent, the alcohols were easier to evaporate, ensuring easy DES regeneration. By adding small amounts of water and methanol, more than 90% of the lipids were recovered in the form of high-purity oils (>90%). In the case of ethanol, a large amount of ethanol was required, which diluted the solvent-rich phase and solubilized more lipids in it. Based on three repeated cycles with the selected antisolvent methanol, > 90% of the eutectic solvent could be regenerated.

(NaPO3)6-modulated reassembly of encapsulated curcumin nanoparticles from yolk granules: Preparation, characterization, and bioavailability

Our previous research has shown that yolk granules can act as a unitary carrier of lipophilic substances. In this study, the Ca2+ content was adjusted using (NaPO3)6 to control the reassembly of yolk granules for curcumin encapsulation to generate yolk granule-curcumin nanoparticles (Gra-Cur NPs). (NaPO3)6 reduced the particle hydrodynamic diameter (Dh). Dissociated granules had the same protein profile as untreated granules, indicating that no new protein subunits were produced. Hydrophobic interaction was the main force of curcumin binding to yolk granules, and curcumin is amorphous after encapsulated. Gra-Cur NPs had excellent thermal and storage stability. Flow cytometry revealed that the rate of HT-29 cell apoptosis and curcumin absorption of encapsulated curcumin was higher than that of curcumin dissolved in DMSO, with smaller Dh. The findings of this study will allow for the development and implementation of bioactive compounds as novel carriers.

Comparative study on the in vitro digestion of different lipids in starch-based Pickering emulsions

Starch-based Pickering stabilizer has attracted more attentions due to its health-friendly attribute. Lipid digestion in Pickering emulsion is the key to its delivery ability for active substances. Herein, in vitro oral-gastric-intestinal digestions of Pickering emulsions stabilized by starch particles with different oil phases (e.g., coconut, corn, olive, and sunflower oils) were investigated. The highest rate of lipid digestion was coconut oil (25.71 %), followed by olive (12.64 %), corn (11.16 %), and sunflower (8.99 %) oils. The lipid digestibility was influenced by saturation of fatty acids: coconut (91.41 %)>olive (16.58 %)>corn (14.63 %)>sunflower (10.85 %) oils. The increase of starch concentration (0.5 % – 4.0 %, w/w) had positive effects, while the increase of oil fraction (25 % – 70 %, v/v) had negative impacts on free fatty acid release due to the formation of different initial droplet sizes. The microstructures observed using confocal laser scanning microscope indicated that starch-based Pickering emulsion possessed super stability against oral and gastric digestions, which made it a superior delivery system for lipophilic active substances under severe gastric environment. These results may promote the design of functional food emulsions stabilized by starch particles which can regulate digestion of triglycerides.

Oral Self-Nanoemulsifying System Containing Ionic Liquid of BX795 Is Effective against Genital HSV-2 Infection in Mice.

BX795 is an emerging drug candidate that has shown a lot of promise as a next-generation non-nucleoside antiviral agent for the topical treatment of herpes simplex virus type-1 (HSV-1) and herpes simplex virus type-2 (HSV-2) infections. Our studies indicated that BX795 has limited oral bioavailability, which could be attributed to its low and pH-dependent solubility. Lipid-based formulations such as self-nanoemulsifying systems (SNESs) can improve the solubility and oral bioavailability of BX795, but the poor lipid solubility of BX795 further limits the development of SNES. To improve the loading of BX795 into SNES, we evaluated the ability of various bulky and biocompatible anions to transform BX795 into an ionic liquid (IL) with higher lipid solubility. Our studies showed that sodium lauryl sulfate and docusate sodium were able to transform BX795 into IL. Compared to pure BX795, the developed BX795 ILs showed differential in vitro cytocompatibility to HeLa cells but exhibited similar in vitro antiviral activity against HSV-2. Interestingly, BX795 docusate (BX795-Doc), an IL of BX795 with ∼135-fold higher lipid solubility than pure BX795, could be successfully incorporated into an SNES, and the developed BX795-Doc-SNES could readily form nanoemulsions of size ≤200 nm irrespective of the pH of the buffer used for dilution. Our in vitro studies showed that BX795-Doc-SNES retained the inherent antiviral activity against HSV-2 and showed similar in vitro cytocompatibility, indicating the availability of BX795 from the SNES in vitro. Finally, orally delivered SNES containing BX795-Doc showed a significant reduction in HSV-2 infection in mice compared to the untreated control. Thus, the transformation of BX795 into IL and the subsequent incorporation of the BX795 IL into the SNES are an effective strategy to improve oral therapy of genital herpes infection.

PHYSICAL-CHEMICAL ANALYSIS OF POLYMER NANOCAPSULES CONTAINING COPAÍBA (Copaifera spp.) AND ANDIROBA (Carapa guianensis Aubl.) VEGETABLE OILS

Vegetable oils are natural products that are in liquid form, volatile, and aromatic, extracted from different parts of plants. In the Amazon region, vegetable oils are traded and sold by the community to increase their family income. Polymeric nanocapsules are nanoparticles composed of an encapsulating agent (biodegradable polymers) such as polycaprolactone, poly(methyl methacrylate), and creatine, which enclose lipophilic substances (active core). The main technological characteristics of these nanostructured systems are the controlled release of active ingredients, biodisponibility, and chemical and physical stability. In this study, nanocapsules containing copaiba and andiroba vegetable oils, as well as their mixtures, were synthesized. The nanocapsules showed particle sizes, Zeta potentials, and polydispersity indices (PDI) ranging from 117 to 218 nm, 28.5 to 35 mV, and 0.130 to 0.251, respectively. The 30/70 ratio (Copaiba/Andiroba) exhibited the most stable mixture among them.