Lipophilic Character Research Articles

Rational design and preparation of superhydrophobic photo-cured hybrid epoxy coating modified by fluorocarbon substituted silsesquioxane-based nanoparticles

Functional superhydrophobic coating has caused intense concern due to its potential applications. A facile and mild dip-coating method is proposed for fabricating superhydrophobic coatings in this work. The epoxy resin (EP) modified by fluorocarbon substituted silsesquioxanes (SQ-F) could be coated on filter paper (FP) and polyurethane sponge (PU), respectively. SQ-F nanoparticles can self-assemble to form multiscale nano-/microstructures during photopolymerization, which improve the hydrophobicity of epoxy. The successful incorporation of SQ-F/EP on filter paper and polyurethane sponge is demonstrated by FT-IR, X-ray photoelectron spectroscopy and energy dispersive spectrometer. SQ-F/EP@FP could separate a series of oil–water mixtures and emulsion effectively with high separation efficiencies over 99.99 %. Furthermore, both liquid pollutant and solid stains are removed by the surface's self-cleaning ability. In comparation with SQ-F/EP@FP, SQ-F/EP@PU with lipophilic and hydrophobic characteristics, possesses oil adsorption capacity about 102 times of its original weight. Moreover, SQ-F/EP@PU could absorb the crude oil within a few minutes and the adsorption capacity reaches as high as 92 times of its original weight.

Analytical investigation of cannabis biomarkers in raw urban wastewater to refine consumption estimates

Wastewater analysis of Δ9-tetrahydrocannabinol (THC) biomarkers can provide essential information on trends in cannabis consumption. Although analysis is mostly focused on the aqueous phase, previous studies have illustrated the need of improving the measurements of raw influent wastewater (IWW) considering also suspended solids. This is important for cannabis biomarkers, because a substantial part of them is expected to be found in the suspended solids due to their more lipophilic character compared with other metabolites/drugs included in these types of studies. However, it remains open to which extent trend estimates might be affected by solely analysing the liquid phase. To investigate this aspect, robust analytical methodologies are required to measure both the liquid and solid phases of IWW. In this work, we firstly tested liquid-liquid extraction (LLE) for THC and its major metabolites (THCOH, and THCCOOH). Using LLE, no filtration or centrifugation step was required for raw IWW analysis, and the three analytes were extracted from both the liquid and the solid phase simultaneously. In parallel, the raw IWW was centrifuged and the obtained solid and liquid phases were analyzed separately: the liquid phase by both LLE and solid phase extraction (SPE) for comparison of data, and the suspended solids by solid-liquid extraction (SLE). The separate analysis of both phases in a number of samples revealed that a significant amount of cannabis biomarkers (ranging from 42 to 90%) was found in the suspended solids. In addition, the total amount of cannabis biomarkers obtained by analysing raw IWW on the one hand, and by separate analysis of the liquid and the solid phases, on the other hand, was in good agreement. Data from this study show that the sole analysis of the liquid phase would lead to a notable underestimation of cannabis biomarkers concentrations in IWW.

Lyophilised nanovesicles loaded with vitamin B12

The use of nanomaterials in recent years has shown many advantages for the production of pharmaceuticals, cosmetics, food, and food packaging. Nanovesicles are emerging as carriers of bio-compounds and drugs at a wide variety of applications due to the hydrophilic and lipophilic character of the structure: an aqueous core surrounded by a lipid layer. In this work, vitamin B12 (cobalamin) was encapsulated, due to its synergic activity with antibiotics. Moreover, this bio compound is present in several food products and pharmaceuticals products. A freeze-drying process is proposed for nanocarriers developments, due to its advantages for storage and transportation. Three types of vesicles formulations were tested: liposomes, niosomes and positively charged niosomes. Maltodextrin at 20 % concentration (w/w) was added to the formulation to protect the vesicles during the lyophilisation process. The nanovesicles particle size and morphology was characterized by Dynamic Light Scattering and Transmission Electron Microscopy, and the encapsulation efficiency by HPLC with UV–vis’s detection. The lyophilised powder was resuspended in three aqueous phases: pure water, glycerol and PEG400 aqueous solutions. An increase in the mean vesicle size was observed as a general trend. It was also studied the effect of adding vitamin B12 before or after the lyophilisation step on mean vesicles size, results indicated that vesicles were less affected in size when vitamin B12 was added before the lyophilisation step. Moreover, encapsulation efficiency (EE) of vitamin B12 in lyophilised vesicles arise values up to 70 % while the loading capacity (LC) of these systems were 100 mg/g, values obtained for liposomes when PEG400 solution was used as hydrating media, showing that the method developed for loaded lyophilised nanocarriers do not alter EE and LC.

Yellow-Emitting Carbon Dots for Selective Fluorescence Imaging of Lipid Droplets in Living Cells.

This study shows a one-pot preparation of carbon dots by a solvothermal method in ethylene glycol. The carbon dots show yellow-colored fluorescence emission in water. The carbon dots showed distinct preference to be present in the hydrophobic environment which was evident from their efficient transfer from aqueous phase to organic phase. They were also found to locate themselves in the vesicle bilayer and micelle core. This inherent lipophilic character of these carbon dots has been successfully utilized for the selective imaging of lipid droplets inside the living cells. The selective imaging of lipid droplets was confirmed by similar staining patterns with other staining dyes and the starvation study.

Insights into the lipophilicity of four commonly prescribed antidiabetic drugs and their simultaneous analysis using a simple TLC-spectrodensitometric method: Application to fixed-dose combination tablets and human plasma

The retention and lipophilicity characteristics of four oral antidiabetic drugs namely; Metformin (MET), Linagliptin (LIN), Empagliflozin (EMP), and Dapagliflozin (DAP) were evaluated by a facile TLC-spectrodensitometric method. The developed method was validated and employed for simultaneous determination of the investigated drugs in their synthetic quaternary mixture, single- and multi-component tablets, and human plasma. The separation of the cited drugs was achieved using silica gel G 60F254-TLC plates and a mobile system consisting of n-butanol: water: glacial acetic acid (7: 3: 1, v/v/v). After scanning at 234 nm, good linearities (10.0–2000.0 ng/band for each drug) and correlation coefficients (r = 0.99882–0.99972) with lower limits of detection and quantitation (2.17–3.58 and 6.57–10.85 ng/band, respectively) were statistically calculated. The obtained recoveries (98.35–101.38%) proved the wide applicability of the established method for concurrent estimation of the studied antidiabetics in fixed-dose combination tablets and human plasma. Besides, the present work was extended to estimate the lipophilicity parameters of the targeted drugs. Molecular lipophilicity (RM), relative lipophilicity (RM0), and lipophilic descriptor (C0) were calculated for MET, LIN, EMP, and DAP. Good correlations (r = 0.8729–0.9933) between the chromatographic retention data and molecular descriptors of the studied drugs were attained. The obtained results confirmed the poor lipophilicity of MET and LIN compared to EMP and DAP. Lastly, understanding the lipophilicity of the cited drugs may be promising for the future design of safer and more effective formulations for diabetes mellitus, cancer, and Alzheimer’s disease. Over and above, this work may be further applied to QSAR studies.

Susceptibility of Angiostrongylus cantonensis Larvae to Anthelmintic Drugs.

Human helminthiasis affects approximately one in five people in the world and disproportionally affects the poorest and most deprived communities. Human angiostrongyliasis, caused by nematode Angiostrongylus cantonensis, is a neglected emerging disease with escalating importance worldwide. Chemotherapy is the main control method for helminthiasis, but the therapeutic arsenal is limited. This study aimed to evaluate the antiparasitic and molecular properties of the major available anthelmintic drugs against A. cantonensis in vitro. The first-stage larvae (L1), isolated from feces of an A. cantonensis-infected rat, were exposed to a set of 12 anthelmintic drugs in vitro. The larvae were monitored, and the concentration- and time-dependent viability alterations were determined. From 12 anthelmintic drugs, six (ivermectin, salamectin, moxidectin, pyrantel pamoate, albendazole and levamisole) were identified to affect the viability of A. cantonensis. The macrocyclic lactones (ivermectin, salamectin, moxidectin) and the imidazothiazole levamisole, were the most effective drugs, with IC50 ranging from 2.2 to 2.9 µM and a rapid onset of action. Albendazole, the most widely used anthelmintic in humans, had a slower onset of action, but an IC50 of 11.3 µM was achieved within 24 h. Molecular properties studies suggest that a less lipophilic character and low molecular weight could be favorable for the biological activity of the non-macrocyclic molecules. Collectively, our study revealed that macrocyclic lactones, levamisole, pyrantel pamoate, and albendazole are important anthelmintic agents against A. cantonensis. The results of this in vitro study also suggest that A. cantonensis L1 may be a particularly sensitive and useful model for anthelmintic studies.

In silico Characterization, ADMET prediction and Molecular Docking studies of few 2/3 carboxylate-4/5/6-monosubstitued indole derivatives as potential GSK-3β inhibitors

Diabetes Mellitus is a leading cause of high mortality rate in the world. Recently, GSK-3β inhibitors showed promising results to treat Diabetes mellitus and several such molecules are in clinical trials. Ethyl 2/3-carboxylate-4/5/6-monosubstituted-1H-indole derivatives were designed with the aim to search new lead molecules. The molecular structures were drawn in ChemBiodraw Ultra© and molecular docking studies were performed by using Schrödinger and AutoDock 1.5.6 software. Few in silico properties such as Log P and toxicity profile were predicted online using SwissADME and PreADMET respectively. Amongst all the designed molecules, few derivatives showed maximum binding affinity in LBD of 6V6L protein. The lipophilic character of the molecules was predicted through their individual Log P Values; molecules with better binding affinities in LBD displayed Log P values of 2.25-3.13. Additionally, some of the designed molecules were subjected to PreADMET for predicting their safety and few were predicted to induce toxic reaction were as others were predicted to be safe in the models that were selected for prediction. Ethyl 2/3-carboxylate-4/5/6-monosubstituted-1H-indole derivative were designed resulting in new molecules with high binding affinities, also few of these molecules were predicted to be non-carcinogenic with low Log P values.

Characterization and Interaction with Biomembrane Model of Benzo[k,l]xanthene Lignan Loaded Solid Lipid Nanoparticles.

Benzo[k,l]xanthene lignans are a group of rare natural products belonging to the class of polyphenols with promising biological activities and are studied as potential chemotherapeutic agents. The lipophilic character of a xanthene core makes these molecules difficult to be used in an aqueous medium, limiting their employment in studies for pharmaceutical applications. To overcome this problem, a drug-delivery system which is able to improve the stability and bioavailability of the compound can be used. In this study, a bioactive benzoxanthene lignan (BXL) has been included in SLN. Unloaded and BXL-loaded SLN have been prepared using the Phase Inversion Temperature method and characterized in terms of size, zeta potential, entrapment efficiency and stability. Differential scanning calorimetry was used to evaluate the thermotropic behavior and ability of SLN to act as carriers for BXL. A biomembrane model, represented by multilamellar vesicles, was used to simulate the interaction of the SLN with the cellular membrane. Unloaded and loaded SLN were incubated with the MLV, and their interactions were evaluated through variations in their calorimetric curves. The results obtained suggest that SLN could be used as a delivery system for BXL.

Lipid-Drug Conjugates and Nanoparticles for the Cutaneous Delivery of Cannabidiol.

Lipid nanoparticles are currently used to deliver drugs to specific sites in the body, known as targeted therapy. Conjugates of lipids and drugs to produce drug-enriched phospholipid micelles have been proposed to increase the lipophilic character of drugs to overcome biological barriers. However, their applicability at the topical level is still minimal. Phospholipid micelles are amphiphilic colloidal systems of nanometric dimensions, composed of a lipophilic nucleus and a hydrophilic outer surface. They are currently used successfully as pharmaceutical vehicles for poorly water-soluble drugs. These micelles have high in vitro and in vivo stability and high biocompatibility. This review discusses the use of lipid-drug conjugates as biocompatible carriers for cutaneous application. This work provides a metadata analysis of publications concerning the conjugation of cannabidiol with lipids as a suitable approach and as a new delivery system for this drug.

In Silico and In Vitro Assessment of Antimicrobial and Antibiofilm Activity of Some 1,3-Oxazole-Based Compounds and Their Isosteric Analogues

In this paper, we report on the antimicrobial activity assessment of 49 compounds previously synthesized as derivatives of alanine or phenylalanine that incorporate a 4-(4-X-phenylsulfonyl)phenyl fragment (X = H, Cl, or Br), namely 21 acyclic compounds (6 × N-acyl-α-amino acids, 1 × N-acyl-α-amino acid ester, and 14 × N-acyl-α-amino ketones) and 28 pentatomic heterocycles from the oxazole-based compound class (6 × 4H-1,3-oxazol-5-ones, 16 × 5-aryl-1,3-oxazoles, and 6 × ethyl 1,3-oxazol-5-yl carbonates). Both in silico and in vitro qualitative and quantitative assays were used to investigate the antimicrobial potential of these derivatives against planktonic and biofilm-embedded microbial strains. Some of the tested compounds showed promising antimicrobial and antibiofilm activity depending on their chemical scaffold and lipophilic character.

Gold(III)-P-chirogenic complex induces mitochondrial dysfunction in triple-negative breast cancer

SummaryChemical agents that specifically exploit metabolic vulnerabilities of cancer cells will be beneficial but are rare. The role of oxidative phosphorylation (OXPHOS) in promoting and maintaining triple-negative breast cancer (TNBC) growth provides new treatment opportunity. In this work, we describe AuPhos-19, a small-molecule gold(III)-based agent bearing a chiral phosphine ligand that selectively disrupts mitochondrial metabolism in murine and human TNBC cells but not normal epithelial cells. AuPhos-19 induces potent cytotoxic effect with half maximal inhibitory concentration (IC50) in the nanomolar range (220–650 nM) across different TNBC cell lines. The lipophilic cationic character of AuPhos-19 facilitates interaction with mitochondrial OXPHOS. AuPhos-19 inhibits mitochondria respiration and induces significant AMPK activation. Depolarization of the mitochondria membrane, mitochondria ROS accumulation, and mitochondria DNA depletion provided further indication that AuPhos-19 perturbs mitochondria function. AuPhos-19 inhibits tumor growth in tumor-bearing mice. This study highlights the development of gold-based compounds targeting mitochondrial pathways for efficacious cancer treatment.

Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2.

The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

Formulation and Evaluation of Apigenin-Loaded Hybrid Nanoparticles.

Apigenin (AGN) is a potent phytochemical with strong antioxidant and anticancer potential. But its therapeutic efficacy is limited due to its high lipophilic characteristics. Therefore, the present investigation aimed to develop AGN-loaded polymer-lipid hybrid nanoparticles (AGN-PLHNPs). Herein, we successfully developed AGN-PLHNPs and optimized them by a 33-Box-Behnken de-sign. The poly (lactic-co-glycolic acid) (PLGA; coded as F1), phospholipon 90 G (PL-90G; coded as F2), and poloxamer 188 (P-188; coded as F3) were considered as the independent factors while particle size (PS; coded as R1), entrapment efficiency (%EE; R2), and cumulative drug release (%CDR; R3) were selected as dependent responses. The average PS, %EE, and %CDR of the AGN-PLHNPs were observed in the range of 101.93 nm to 175.26 nm, 58.35% to 81.14%, and 71.21% to 93.31%, respectively. The optimized AGN-PLHNPs revealed better homogeneity (poly-dispersity index < 0.2) and colloidal stability with high zeta potential (>25 mV). It also exhibited fast release in the initial 4 h after that sustained release up to 48 h of study. Moreover, the results of both DPPH as well as ABTS assays revealed significant improvement in the antioxidant activity. Furthermore, the optimized AGN-PLHNPs exhibited enhanced cytotoxicity efficacy against MCF-7 as well as MDA-MB-231 breast cancer cell lines.

Antitumor and antileishmanial activities of limonene-thiosemicarbazones bearing heterocycles nucleous

In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based thiosemicarbazones containing different pentacyclic heterocyclic nucleus moiety focused in the search of novel antitumor and antileishmanial agents. In the antitumor assay, the derivative imidazole of S-(-)-limonene 8 was the most active compound, especially for U-251, UACC-62 and K562 human tumor cell lines with GI50 ranging from 1.0 to &lt;0.25 µg.mL-1. On the other hand, the imidazole-thiosemicarbazone of R-(+)-limonene 4 was the most promising derivative against the promastigote form of L. amazonensis (IC50=5.9µM). Meanwhile, thiosemicarbazones without limonene moiety (9-12) showed the lowest activities in the biological assays performed. The results demonstrated the influence of the lipophilic molecular character and stereochemistry of chiral monoterpene on the evaluated activities.

Optimizing Use of DMI Fungicides for Management of Apple Powdery Mildew Caused by Podosphaera leucotricha in New York State.

Powdery mildew, caused by the ascomycete Podosphaera leucotricha, is an endemic disease found wherever apples are grown that reduces both tree vigor and fresh market yield. In the absence of durable host resistance, chemical management is the primary means of disease control. Demethylation inhibitor (DMI) fungicides are widely used to manage apple powdery mildew, but members within this fungicide class have been observed to differ in efficacy with respect to disease control. Moreover, debate exists as to the optimal timing of DMI fungicide applications for management of apple powdery mildew. In this regard, the goal of this study was to determine the best-use practices for DMI fungicides to manage apple powdery mildew in New York State. Multiyear trials were conducted to evaluate the potential differential efficacy performance of four common DMI fungicides, and additional trials were conducted to assess optimal application timing. In all years, we observed that treatments of flutriafol and myclobutanil consistently had the lowest incidences of powdery mildew compared with difenoconazole and fenbuconazole. In the 2018 and 2021 trials, the newly registered mefentrifluconazole was more comparable to the difenoconazole program with respect to powdery mildew disease incidence. We hypothesize that differences in DMI efficacy may result from each fungicide's water solubility and lipophilicity characteristics and thus their ability to move systemically in the host or more easily penetrate the surface of germinating conidia. Applications timed between petal fall and first cover resulted in the lowest incidence of powdery mildew on terminal leaves of apple shoots compared with applications timed before petal fall. These observations are contrary to previous studies conducted in regions with differing climates. We also found that the incidence of secondary powdery mildew observed 2 weeks after petal fall was influenced by applications of DMI fungicides during the previous season. For example, management programs consisting of applications of flutriafol or myclobutanil in the previous season tended to have lower incidence of apple powdery in the next spring, presumably because of reductions in overwintering inoculum. Despite reports of DMI resistance in other apple pathosystems, the DMI fungicide class is still relevant for the successful management of apple powdery mildew in New York State.

Synthesis and evaluation of sulfosuccinate-based surfactants as counterions for hydrophobic ion pairing

Hydrophobic ion pairing is a promising strategy to raise the lipophilic character of therapeutic peptides and proteins. In past studies, docusate, an all-purpose surfactant with a dialkyl sulfosuccinate structure, showed highest potential as hydrophobic counterion. Being originally not purposed for hydrophobic ion pairing, it is likely still far away from the perfect counterion. Thus, within this study, docusate analogues with various linear and branched alkyl residues were synthesized to derive systematic insights into which hydrophobic tail is most advantageous for hydrophobic ion pairing, as well as to identify lead counterions that form complexes with superior hydrophobicity. The successful synthesis of the target compounds was confirmed by FT-IR, 1H-NMR, and 13C-NMR. In a screening with the model protein hemoglobin, monostearyl sulfosuccinate, dioleyl sulfosuccinate, and bis(isotridecyl) sulfosuccinate were identified as lead counterions. Their potential was further evaluated with the peptides and proteins vancomycin, insulin, and horseradish peroxidase. Dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate significantly increased the hydrophobicity of the tested peptides and proteins determined as logP or lipophilicity determined as solubility in 1-octanol, respectively, in comparison to the gold standard docusate. Dioleyl sulfosuccinate provided an up to 8.3-fold higher partition coefficient and up to 26.5-fold higher solubility in 1-octanol than docusate, whereas bis(isotridecyl) sulfosuccinate resulted in an up to 6.7-fold improvement in the partition coefficient and up to 44.0-fold higher solubility in 1-octanol. The conjugation of highly lipophilic alkyl tails to the polar sulfosuccinate head group allows the design of promising counterions for hydrophobic ion pairing. Statement of significanceHydrophobic ion pairing enables efficient incorporation of hydrophilic molecules into lipid-based formulations by forming complexes with hydrophobic counterions. Docusate, a sulfosuccinate with two branched alkyl tails, has shown highest potential as anionic hydrophobic counterion. As it was originally not purposed for hydrophobic ion pairing, its structure is likely still far away from the perfect counterion. To improve its properties, analogues of docusate with various alkyl tails were synthesized in the present study. The investigation of different alkyl residues allowed to derive systematic insights into which tail structures are most favorable for hydrophobic ion pairing. Moreover, the lead counterions dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate bearing highly lipophilic alkyl tails provided a significant improvement in the hydrophobicity of the resulting complexes.

Oxalic acid in ginger specifically denatures the acrid raphides in the unprocessed dried tuber of Pinellia ternata

Abstract Objective: Pinellia Tuber, the dried tuber of Pinellia ternata, is widely used in Japanese Kampo medicines and traditional Chinese medicines. The unprocessed Pinellia Tuber is known to cause very strong acrid irritation at oral and laryngopharynx mucosa. Recent studies have shown that the sharp needle-like crystals called raphides, that are composed of calcium oxalate and proteins, are the main causative substances of the irritation. Ginger, the rhizome of Zingiber officinale, has been used in the processing to reduce the acridity of Pinellia Tuber since before the sixth century, however, the mechanisms of reducing acridity have not been scientifically proved yet. Methods: We developed the raphides denaturation assay (RDA) to quantify the degree of denaturation in the raphides to cause irritation. By their lipophilic characters, the raphides could be extracted in petroleum ether (PE) layer from powdered Pinellia Tuber suspended in water, and the contents of the raphides in PE layer were measured by the absorbance. By this assay, we conducted the activity-guided fractionation from the boiling water extract of ginger to find the ingredients to denature the raphides. We also conducted the gustatory tests to detect the change of the irritation of the denatured raphides. Results: The treatment of powdered Pinellia Tuber suspension with ginger extract reduced the distribution of raphides in PE layer in RDA in a concentration-dependent manner. The activity-guided fractionation using RDA revealed that oxalic acid was the main active ingredient in ginger extract to denature the raphides of Pinellia Tuber. Oxalic acid reduced the lipophilicity of the raphides in the thermo-, time-, and concentration-dependent manners, and its activity was affected by pH. The treatment of powdered Pinellia Tuber suspension with oxalic acid significantly reduced its acrid irritation in gustatory test in human. Conclusions: We found that oxalic acid is the main active ingredient in ginger to reduce the acrid irritation of Pinellia Tuber.

Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients

Introduction: With its large surface area, skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics, skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue. Objective: In order to characterize the vertical and lateral movement of molecules into and inside the skin, the diffusivity of active ingredients with different physicochemical properties and their penetration ability in different dermal skin layers was investigated. Methods: A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep-implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography measurement. Results: The depth depended penetration of superficial and deep-implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight but different lipophilic characteristics, were tested for their penetration ability inside a propylene glycol and oleic acid formulation. Conclusion: The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influences the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.

Modified 7-Chloro-11H-indeno[1,2-b]quinoxaline Heterocyclic System for Biological Activities

Recent advances in functionalized organic Spiro heterocyclic compounds composed of nitrogen bonded five- and six-membered rings have been made, establishing them as a synthetic target in organic-based biomedical applications. In this work, we report a synthesis of spirocyclic compounds under a one-pot reaction using 1,3-dipolar cycloaddition in a regio and diastereoselective manner. The higher atomic economy with higher yield (95%) and regio and stereoselectivity were achieved by a multi-component reaction of L-proline (1), Indenoquinoxaline (2), and the dipolarophile of malononitrile (3) solvents followed by reflux conditions. The reaction intermediate comprised azomethineylides derived from reactive primary amines, and the spiro derivatives were synthesized up to a ≈ 95% yield. The structural and characteristic chemical components of the as-prepared Spiro compounds were characterized by 1H-NMR, FTIR, and Mass spectroscopy. The functionalized spiro-pyrrolizidines were found to be effective for biological uses by considering their in vitro screening and antimicrobial impacts. Spiro constituents were found to be much more effective for Gram-positive bacteria due to the stronger lipophilic character of the molecules, and they resulted feasible membrane permeation in a biological system. Based on the planarity geometry of the Spiro pyrrolizidines, meta-substitution possesses steric hindrance and hence shows less effectiveness compared to para-substitution on the same nucleus, which shows a marginal steric effect. The biological studies showed that the derived spiro heterocyclic systems have an inhibitory effect of 50%.

Liposome: A Novel Drug Delivery System

Liposome was derived from two Greek words “Lipos meaning fat and Soma meaning body”. Liposome were spherical shaped vesicles consist of phospholipids and cholesterol. Due to their size hydrophobic and lipophilic character they are very promising system for drug delivery. This novel drug delivery system aims to target the drug directly to the site of action. Liposomes are very biocompatible and stable and have unique property to entrap both hydrophilic drug and lipophilic drug to its compartment and lead to controlled release effect. They are of 0.05- 5.0 micrometer in diameter. Liposomes are used for the treatment of various diseases like tumors or cancer. Liposomal Drug Delivery System and various aspects related to liposome that can be studied Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. This review describes liposomes structure, composition, preparation methods, and evaluation clinical applications