Cell Permeability Studies Research Articles

Increasing the bioavailability of curcumin using a green supercritical fluid technology-assisted approach based on simultaneous starch aerogel formation-curcumin impregnation

A green approach based on simultaneous starch aerogel formation-curcumin impregnation via supercritical fluid technology was used to increase the bioavailability of curcumin. The loading amounts of curcumin were 16.4, 21.4, and 24.9 mg/g of aerogel for the 25% Amyl-loaded, 55% Amyl-loaded, and 72% Amyl-loaded samples, respectively. Curcumin-loaded aerogels showed the eventual distribution of curcumin in the hydrophobic area of the internal structure of the aerogels. In vitro gastrointestinal release profiles demonstrated the enhanced curcumin release from the curcumin-loaded aerogel formulations produced by the SC-CO2 technology over free curcumin. After intestinal digestion, the percentage of released curcumin from 25% Amyl-loaded, 55% Amyl-loaded, and 72% Amyl-loaded was 7.2, 12.1, and 12.1%, respectively, while the release of native curcumin was only 0.5%. Caco-2 cell permeation studies revealed superior bioavailability of curcumin from the curcumin-loaded aerogels. Curcumin-loaded aerogels exhibited improved storage stability than free curcumin.

Oral self-nanoemulsifying drug delivery systems for enhancing bioavailability and anticancer potential of fosfestrol: In vitro and in vivo characterization

PurposeThe objective of the current research work was to fabricate a fosfestrol (FST)-loaded self-nanoemulsifying drug delivery system (SNEDDS) to escalate the oral solubility and bioavailability and thereby the effectiveness of FST against prostate cancer. Methods32 full factorial design was employed, and the effect of lipid and surfactant mixtures on percentage transmittance, time required for self-emulsification, and drug release were studied. The optimized solid FST-loaded SNEDDS (FSTNE) was characterized for in vitro anticancer activity and Caco-2 cell permeability, and in vivo pharmacokinetic parameters. ResultsUsing different ratios of surfactant and co-surfactant (Km) a pseudo ternary phase diagram was constructed. Thirteen liquid nano emulsion formulations (LNE-1 to LNE-13) were formulated at Km = 3:1. LNE-9 exhibited a higher % transmittance (99.25 ± 1.82 %) and a lower self-emulsification time (24 ± 0.32 s). No incompatibility was observed in FT-IR analysis. Within 20 min the solidified FST loaded LNE-9 (FSTNE) formulation showed almost complete drug release (98.20 ± 1.30 %) when compared to marketed formulation (40.36 ± 2.8 %), and pure FST (32 ± 3.3 %) in 0.1 N HCl. In pH 6.8 phosphate buffer, the release profiles are found moderately higher than in 0.1 N HCl. FSTNE significantly (P < 0.001) inhibited the PC-3 prostate cell proliferation and also caused apoptosis (P < 0.001) compared to FST. The in vitro Caco-2 cell permeability study results revealed 4.68-fold higher cell permeability of FSTNE than FST. Remarkably, 4.5-fold rise in bioavailability was observed after oral administration of FSTNE than plain FST. ConclusionsFSTNE remarkably enhanced the in vitro anticancer activity and Caco-2 cell permeability, and in vivo bioavailability of FST. Thus, FST-SNEDDS could be utilized as a potential carrier for effective oral treatment of prostate cancer.

Polymer selection for amorphous solid dispersion of a new drug candidate by investigation of drug polymer molecular interactions.

The antitumor drug candidate X-05 is being developed as an innovative anti-lung cancer drug candidate due to its excellent antitumour activity. A Caco-2 cell permeability study and solubility study confirmed that X-05 belonged to BCS class or compounds. Therefore, the main challenge is to develop appropriate preparations for preclinical studies and further clinical phase research. By evaluating the preliminary results of kinetic solubility in biorelevant media and the structural analysis of X-05 and polymers, three polymers PVP K30, PVP VA 64 and HPMCAS, which may have intermolecular interactions with X-05, were chosen to select the optimal carrier for X-05 to prepare amorphous solid dispersions (ASDs). ASD X-05-PVP VA 64 was selected as the optimal polymer by evaluating its kinetic solubility in biorelevant media and solid stability. The physical and chemical properties of ASD X-05-PVP VA 64 remain stable when the drug loading is as high as 50%. The drug-polymer interactions of ASD X-05-PVP VA 64 were studied by ultraviolet spectrophotometry, nuclear magnetic resonance spectrometry, infrared and Raman spectrophotometry, and the results indicated that the intermolecular hydrogen bond interaction between the drug and polymer was the foundation of the solubilization and stabilization of X-05 in PVP VA 64.

Bacterial cell permeability study by metal oxide and mixed metal oxide nanoparticles: analysis of the factors contributing to the antibacterial activity of nanoparticles.

In this work, we investigate the nanoparticle-cell wall interaction by NiO and mixed metal oxide CuO-NiO nanoparticles. We have synthesized and characterized the nanoparticles using XRD, FESEM, EDS, UV vis. spectroscopy, FTIR, Zeta, and TEM analysis in our previous work. Furthermore, a preliminary antibacterial study showed that both the nanoparticles performed very well as antibacterial agents. In this extended work, we investigate the mechanism of interaction of NiO and CuO-NiO nanoparticles with S. aureus and E. coli cells as there are number of studies for antibacterial mechanism of CuO nanoparticles. The uptake of crystal violet dye in the outer bacterial membrane, the release of ß-galactosidase enzyme, and relative electric conductivity assay were used to investigate changes in the permeability and integrity of the cell membrane. Superoxide ions, which are produced intracellularly as ROS by nanoparticles, severely damage bacterial membranes. Zeta potential measurement, which resulted in surface charge neutralization, proved membrane instability. FTIR analysis was used to identify changes in the proteins, carbohydrates, and fatty acids that make up the chemical composition of cell surfaces. AFM imaging demonstrated extensive alteration of the nanomechanical and surface characteristics. Confocal microscopy examination supported the DNA fragmentation and nanoparticle-cell adhesion. Due to their enhanced antibacterial activity when compared to monometallicoxide nanoparticles, this study demonstrated that mixed metal oxides can be employed in the health and biomedical sectors.

Methylprednisolone 100 mg tablet formulation with pea protein: experimental approaches over intestinal permeability and cytotoxicity

Objective This study was carried out to transform the hydrolyzed pea protein into a pharmaceutical tablet form by masking methylprednisolone. Significance This study provides some crucial contributions in showing how functional excipients such as pea protein, which are generally used in food industries, can be used in pharmaceutical product formulations and their effects. Methods Methylprednisolone was formulated using spray drying technology. Design Expert Software (Version 13) was used for the statistical analysis. The in vitro cytotoxic effects for NIH/3T3 mouse fibroblast cells were investigated by XTT cell viability assay. HPLC was used to analyze the Caco-2 permeability studies and dissolution tests. Results The optimum formulation was evaluated against the reference product by performing cytotoxicity and cell permeability studies. According to our test results, Papp (apparent permeability) values of Methylprednisolone were measured around 3 × 10-6 cm/s and Fa (fraction absorbed) values around 30%. These data indicate that Methylprednisolone HCl has ‘moderate permeability’ and our study confirmed that it could have belonged to BCS Class II-IV since both low solubility and moderate permeability. Conclusion The findings offer valuable information to guide and inform the use of pea protein in pharmaceutical formulations. Significant effects on methylprednisolone tablet formulation designed with the philosophy of quality by design (QbD) of pea protein have been demonstrated by both in vitro and cell studies.

Development, characterization and Caco-2 cells absorption of curcumin solid dispersion for oral administration

Curcumin is an active dietary compound. However, its low solubility and rapid metabolism limit its absorption in the gastrointestinal (GI) tract and reduces its systemic bioavailability. To overcome these drawbacks, curcumin solid dispersion (CSD) was developed employing polyvinylpyrrolidone (PVP) as a carrier without and with soybean phospholipids (SP) as a co-carrier and prepared using a melting solvent method. The influence PVP and SP on physicochemical properties and in vitro permeability of CSD was investigated. Curcumin in all developed CSD demonstrated amorphous state as confirmed by X-ray diffraction. Spherical particles of ∼140 nm and ∼190 nm were obtained when CSD without and with SP was diluted with water. Consequently, CSD without and with SP possessed significantly greater curcumin water solubility of ∼4200-fold and ∼6500-fold, respectively, as compared to free curcumin, which leading to enhanced curcumin absorption across Caco-2 cell. The dissolution studies, both in 0.1 N HCl and phosphate buffer pH6.8, of CSD showed that curcumin was quickly and completely dissolved within 5 min. Caco-2 cell permeation studies revealed that CSD with SP presented a lag time with slightly lower curcumin absorption than CSD without SP. Moreover, the physical and chemical stability of CSD was found to be stable for up to 6 months at 4 °C and room temperature. From these findings, CSD could be beneficial for enhancing the oral absorption profiles of curcumin.

Development, validation and application of a gas chromatography method for the determination of dillapiole from Piper aduncum essential oil in skin permeation samples.

The essential oil extracted from the leaves of Piper aduncum has antifungal, insecticidal and antibacterial activity. Studies with its main compound, dillapiole (DIL) revealed antibacterial and anti-inflammatory potential. Despite all this bioactivity, there is no updated report on the development and validation of analytical and bioanalytical methodology to quantify DIL in skin samples. A selective, precise, accurate and adequate method for the determination of DIL in solutions, porcine ear skin samples and receptor fluid was developed and validated by headspace extraction-gas chromatography with flame ionization detection (HS-GC-FID). HS-GC-FID was applied to determine DIL in Franz cell permeation and retention studies using porcine ear skin samples. In the HS-GC-FID method, matrix-related interferences were not observed at the peak of the DIL retention time. The results showed a high recovery (>97%) after the extraction procedure, allowing the quantification of DIL in complex matrices. In vitro permeation/retention for DIL showed cumulative amounts permeated in the order: receptor fluid (21.98 ± 1.19 μg/cm2 ) > epidermis (15.40 ± 1.20 μg/cm2 ) > dermis (9.52 ± 1.13 μg/cm2 ). HS-GC-FID was successfully validated and the results point to DIL transdermal permeation and to the potential to develop pharmaceutical formulations for skin delivery to treat inflammation or infections.

Nonbenzenoid BODIPY Analogues: Synthesis, Structural Organization, Photophysical Studies, and Cell Internalization of Biocompatible N-Alkyl-Aminotroponyl Difluoroboron (Alkyl-ATB) Complexes.

The alkyl-BODIPY derivatives are lipid types of fluorescent molecules that exhibit a unique structure and functions including sensing of hydrophobic microenvironments in living cells. Their synthesis involves multisteps from the core structure dipyrromethene scaffold. The alkyl-BODIPY analogues are sought to derivatize with minimal synthetic steps even by altering the core structures derived from benzenoid aromatic moiety. Recently, the nonbenzenoid scaffold (aminotropone) has been explored to synthesize troponyl-BODIPY analogues, which are fluorescent. In the repertoire of nonbenzenoid analogue, N-alkyl-aminotroponyl difluoroboron (alkyl-ATB) is rationally designed comprising long-chain hydrocarbons to explore the lipid type of fluorescent molecules. This report describes the synthesis, photophysical studies, structural organization, and biocompatibilities of ATB derivatives containing different lengths of alkyl chain at 2-aminotropone scaffold. The photophysical studies of ATB derivatives reveal their fluorescence behaviors in organic solvents (CH3OH/CH3CN) with a quantum yield of ∼10 to 15%. These ATB derivatives also exhibit fluorescence characters in the solid state though their quantum yield is relatively low. Cell permeability and cytotoxicity studies reveal that alkyl-ATB derivatives are permeable to HeLa/HEK293T cell lines and show negligible cytotoxicity. The biocompatibility of alkyl-ATB derivatives is studied and confirmed by cell viability (MTT) assay to the HeLa/HEK293T cell lines. Importantly, the cell internalization studies of the representative alkyl-ATB molecule by fluorescence microscopy show that octyl-ATB is efficiently detectable at the cytoplasmic membrane and cellular nucleus in HeLa cells. Hence, alkyl-ATB derivatives are potential fluorescent molecules for developing probes to visualize cellular components under a fluorescence microscope.

Development of Lipid-Drug Conjugate Nanoparticles for Hydrophilic and Lipophilic Drug: A Comparative Ex vivo Gut and Caco-2 Cell Permeability Study

Background: The lipid-drug conjugate nanoparticles (LDC NPs), amongst other lipidbased nanoparticles, are the most accepted ones for the oral delivery of both hydrophilic and hydrophobic drugs with poor bioavailability. Besides, the LDC NPs show altered physicochemical properties of the drug and have the potential applications in targeting the drug to a specific organ. Objective: To synthesize hydrophilic Valacyclovir (VACV)-stearic acid (SA) and lipophilic Acyclovir (ACV)-stearic acid conjugates (VACV-SAC and ACV-SAC), and develop their nanoparticles (VACV-LDC-NPs and ACV-LDC-NPs) for improved intestinal permeability. Methods: Both VACV-SAC and ACV-SAC were synthesized and confirmed using FTIR, NMR, and DSC techniques and characterized for assay. The lipid drug conjugate nanoparticles (LDC NPs) were prepared using cold high-pressure homogenization technique and characterized for drug content, mean particle size, zeta potential, ex vivo gut permeability using rat gut sac model, and Caco-2 cell permeability. Results: The FTIR, NMR, and DSC results confirmed the successful synthesis of LDCs. The assay of VACV-SAC and ACV-SAC was found to be 51.48±5.6% and 41.2±6.2%, respectively. The VACV-LDC-NPs and ACV-LDC-NPs showed %EE of 99.10±6.71% and 86.84±5.32%, the mean particle size of 338.7±8nm and 251.3±7nm and zeta potential of -10.8±2.31mV and -11.2±3.52mV respectively. About 91±5.2% of VACV and 84±6.5% of ACV were found permeated across the rat intestine after 480 minutes from their respective NPs. Furthermore, VACV-LDC-NPs and ACVLDC- NPs displayed a significantly higher permeability coefficient (61.5×10-6 and 59.8×10-6 cm/s, respectively) than their plain solutions. Conclusion: The obtained remarkable permeability characteristics indicate developed LDC NPs are the potential, promising and translational approaches for effective oral delivery of poorly bioavailable hydrophilic and lipophilic drugs. Furthermore, this approach may result in moderately to significantly enhanced oral bioavailability of hydrophilic drugs as the conjugation results in amphiphilic molecules, which are further absorbed through different mechanisms across the intestinal mucosa (mainly through passive diffusion mechanism).

Gallic acid-loaded microemulsion and microemulsion gel: Development, characterization, and evaluation of antioxidant effectiveness

In this study, it was aimed to develop, characterize, and improve the antioxidant activity of gallic acid (GA) by formulating it into microemulsion (ME) and microemulsion gel (MEg). Blank MEs were prepared using different proportions of oil/water/surfactant, which provide stable and transparent ME production. Their droplet sizes, zeta potentials and stabilities after holding, centrifugation, and freeze-thawing processes were determined. F2 and F5 coded MEs were selected among the blank MEs and GA was loaded into these formulations. Besides the characterization studies, pH and viscosity measurement, in vitro release, cytotoxicity test, cell permeation, and antioxidant activity studies were performed. In vitro released amount of GA was enhanced by formulating it into ME and MEg at the end of six hours and it showed a scavenging effect of DPPH ● and ABTS ●+ radicals. In conclusion, increased efficacy, reduced toxicity, and prolonged antioxidant activity have been achieved with the use of new, non-toxic, and stable ME and MEg loaded with GA and it is thought that these formulations create the potential for topical application.

Bi-functional NiO-ZnO nanocomposite: Synthesis, characterization, antibacterial and photo assisted degradation study

NiO–ZnO mixed metal oxide nanocomposite was synthesized via chemical homogeneous precipitation method. The synthesized nanocomposite was also characterized by XRD, FESEM with EDS, FTIR, and UV. XRD exhibit an average crystallite size of 29 nm. The elemental composition obtained from EDS shows a nearly equal concentration of Ni and Zn with an atomic ratio of Ni/Zn = 0.96. The particles of nanocomposite are highly stable throughout a wide range of pH. The DLS exhibit an average hydrodynamic particle size ~49 nm. The high pore diameter and pore volume of nanocomposite obtained from BET exhibited a high photocatalytic activity for the removal of methylene blue (MB) dye under UV light irradiation. The kinetics of photocatalytic reduction of MB followed the Langmuir isotherm model, suggesting homogeneous surface adsorption of MB on the surface of the nanocomposite. NiO-ZnO nanocomposite was also found to be an effective antibacterial agent against Gram positive bacteria (Staphylococcus aureus) and Gram negative bacteria (Escherichia coli). Colony forming unit plate counting method showed that 95% and 85% of S. aureus and E. coli respectively were killed by the nanocomposite. Also, this suggested that nanocomposite was more effective towards S. aureus than E. coli. Release of intracellular components was evident from FESEM image of nanocomposite-bacteria cell, cell integrity study, and cell permeability study. This included the release of electrolytes, nucleic acid, and proteins, ultimately leading to cell lysis.

Bioavailability and Dissolution Rate Enhancement of an Anticancer Drug Bicalutamide by Encapsulation into Mesoporous Silica Nanoparticles: Effects of Amine Functionalization and Caco-2 Cell Permeability Study

Abstract: Background: The present study was undertaken with the aim of dissolution rate and Bioavailability enhancement of anticancer drug Bicalutamide (BIC) via encapsulation into mesoporous silica nanoparticles (MSNs). Materials and Methods: The bare (MCM-41) and surface decorated MSNs were subjected to thorough characterization pre and post drug loading by Fourier transform infrared spectroscopy, Nitrogen sorption analysis, Differential Scanning Calorimetry, Thermogravimetric analysis, Small angle and wide angle X-ray diffraction, Scanning electron microscopy and Transmission electron microscopy. Introduction of Nitrogen post functionalization was confirmed by the elemental analysis. Synthesized MSNs were surface decorated with amine groups (AMN-MSN) and in-depth study of effect of functionalization and food on dissolution kinetics was done. Developed MSNs and AMN-MSNs were thoroughly characterized pre and post BIC loading. In vitro intestinal permeability study was performed to determine the apparent permeability of synthesized MSNs. The formulations were also investigated for their in vivo behaviour by oral administration to male Swiss albino mice and various pharmacokinetic parameters calculated. Results: A significant increase in permeability was obtained the dissolution rate and bioavailability were found to be 3.12 and 2.71 times enhanced in MCM-41 as comparison to the BIC suspension. Conclusion: Thus, MSNs could serve as an effective platform for delivering of various anti-cancer drugs and enhancing their efficiency. Key words: Bicalutamide, Functionalized Mesoporous silica nanoparticles, Dissolution, Caco-2 cells permeability, Bioavailability.

Cyclodextrin nanoparticle bound oral camptothecin for colorectal cancer: Formulation development and optimization.

Chemotherapeutic drugs for colorectal cancer(CRC) which is currently the third most lethal cancer globally, are administered intravenously (iv) due to their low oral bioavailability resulting from their physicochemical properties. Non-selective biodistribution and difficulties of parenteral administration reduce treatment efficacy. The aim of this work is to develop cyclodextrin (CD) based cationic nanoparticles (NPs) for CRC treatment with model drug camptothecin (CPT) that can be administered orally, protecting CPT through gastrointestinal tract (GIT), accumulating at mucus layer and providing an effective local treatment for the tumor area. NPs using two different amphiphilic CDs were prepared and coated with polyethylenimine (PEI) or chitosan (CS) to obtain positively charged surface for all formulations. Pre-formulation studies resulted in optimal formulation, CPT loaded Poly-β-CD-C6 NPs, with 135nm diameter and zeta potential of+40mV. In vitro release study was designed to represent gastrointestinal pH and transit time revealing 52% of encapsulated CPT successfully delivered all the way to simulated colon. CPT bound to Poly-β-CD-C6 NPs exhibited higher cytotoxicity on HT-29 cells compared to equivalent CPT in solution. Caco-2 cell permeability studies showed 276% increase in CPT permeability and significantly higher mucosal penetration in cationic CD nanoparticle form.

Hyperglycemia-induced ubiquitination and degradation of β-catenin with the loss of platelet endothelial cell adhesion molecule-1 in retinal endothelial cells.

Increased retinal vascular permeability is one of the earliest manifestations of diabetic retinopathy. The aim of this study was to investigate the role of hyperglycemia-induced platelet endothelial cell adhesion molecule-1 loss on retinal vascular permeability via the β-catenin pathway. Type I diabetes was induced in male Wistar rats using streptozotocin injections, with age-matched non-diabetic rats as controls. Rat retinal microvascular endothelial cells were grown under normal or high glucose conditions for 6days. Small interfering Ribonucleic Acid was used to knock down platelet endothelial cell adhesion molecule-1 in rat retinal microvascular endothelial cells for loss-of-function studies. Retinas and rat retinal microvascular endothelial cells were subjected to Western blot, immunofluorescence labeling, and co-immunoprecipitation analyses to assess protein levels and interactions. A biotinylated gelatin and fluorescein isothiocyanate-avidin assay was used for retinal endothelial cell permeability studies. β-catenin, β-catenin/platelet endothelial cell adhesion molecule-1 interaction, active Src homology 2 domain-containing protein tyrosine phosphatasewere significantly decreased, while β-catenin ubiquitination levels and endothelial permeability were significantly increased, in hyperglycemic retinal endothelial cells. Similar results were observed with platelet endothelial cell adhesion molecule-1 partial knockdown, where β-catenin and active Src homology 2 domain-containing protein tyrosine phosphatase levels were decreased, while phospho-β-catenin and retinal endothelial cell permeability were increased. Platelet endothelial cell adhesion molecule-1 loss may contribute to increased retinal endothelial cell permeability by attenuating β-catenin levels under hyperglycemic conditions.

Development, characterization and evaluation of topical methotrexate-entrapped deformable liposome on imiquimod-induced psoriasis in a mouse model.

The aim of this study was to prepare and characterize topical methotrexate (MTX) with different percentages (0.05%, 0.1%, 0.25% and 0.5%) entrapped in deformable liposomes using phosphatidylcholine and oleic acid. The effectiveness and sub-acute toxicity of these topical formulations were investigated in imiquimod (IMQ)-induced psoriasis in a mouse model (IMQP). The particle sizes of formulations were around 100 nm with a mean zeta potential of -72.87 mV. The entrapment efficiency (EE%) of MTX in liposomal formulations were more than 85%. Franz cell permeability studies indicated that permeation of MTX through the healthy BALB/c mice skin is very low; however, in the inflammatory skin, which was induced by IMQ it was significant (50%). Liposomal MTX (LM 0.05 and 0.1%) caused significant reduction of thickness score dose-dependently in IMQP compared to the injected MTX. Moreover, investigation of the inflammatory factor and pathological examinations of skin proved the superiority of the LM treating group. Pathological examinations also showed there are no toxicity in organs of the mice that received the LM. Blood cell count test didn't show any abnormality. MTX-entrapped deformable liposomes could be a topical option in future for the treatment of human psoriasis with a less toxicity and merit further investigations.

Formulation of Dronedarone Hydrochloride-Loaded Proliposomes: In Vitro and In Vivo Evaluation Using Caco-2 and Rat Model.

The objective of the present study was to develop a proliposomal formulation to increase the oral bioavailability of dronedarone hydrochloride (dronedarone HCl) by enhancing solubility, dissolution, and/or intestinal absorption. Proliposomes were prepared by using solvent evaporation method. In this process, different ratios of drug, phospholipids, such as soy phosphatidylcholine (SPC), Phospholipon 90H, hydrogenated egg phosphatidylcholine (HEPC), and dimyristoyl phosphatidylglycerol (DMPG), and cholesterol were used. Physical characterization and in vitro dissolution studies were evaluated for the prepared formulations. In vitro transport across the membrane was carried out using Caco-2 cells. Among all the formulations, the amount of drug released in dissolution was higher with DPF8 formulation (drug:DMPG Na:cholesterol:::1:2:0.2) compared to the pure drug. Also, Caco-2 cell permeability studies resulted in 2.6-fold increase in apparent permeability. Optimized formulation was evaluated in vivo in male Sprague-Dawley rats. After single oral administration of optimized formulation (DPF8), a relative bioavailability of 148.36% was achieved compared to the pure drug. Improved oral bioavailability of dronedarone could be provided by an optimized proliposomal formulation with enhanced solubility, permeability, and oral absorption.

Novel Strategy for the Systemic Delivery of Furosemide Based on a New Drug Transport Mechanism.

We reported a novel transport mechanism of curcumin, independent of improved solubility, which involved direct contact of amorphous solid particles with the cell membrane. This mechanism has potential as a novel systemic delivery system of poorly water-soluble drugs. In this study, the transport mechanism of furosemide (FUR), which is transported by the same novel mechanism, was examined. In vitro cell permeation studies under air-interface conditions (AICs) revealed that the permeation from powders sprayed on cell monolayers was significantly higher than that under liquid-covered conditions (LCCs) from their solutions. The permeation from amorphous solid particles was faster than that from crystals. Similar results were derived from in vitro studies using an artificial membrane, with which the permeation of FUR could be examined without water. These findings clearly indicated that the transport mechanism of FUR is the same as that of curcumin. For the application of this new transport mechanism, the in vivo absorption of FUR was examined after pulmonary insufflation, which allows the solid particles to make direct contact with the epithelial cells. Pulmonary absorption of FUR from the amorphous powder was almost complete and was faster than that after intragastric administration of the solution, suggesting that FUR was absorbed from the lung by the same mechanism as the in vitro study. This new transport mechanism, which is independent of water dissolution, could be exploited to develop a novel delivery system for poorly water-soluble drugs, using pulmonary powder inhalation.

A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across Air Interface Respiratory Epithelia.

The purpose of this study was to present a novel and simple drug deposition method to evaluate drug transport of aerosol microparticles across airway epithelial cells. Microparticles containing ciprofloxacin HCl (Cip) and doxycycline (Dox), alone or in a 50:50% w/w ratio, were spray dried and suspended using 2H, 3H-perfluoropentane, model propellant. The suspension was then used to assess deposition, and transport of these drug microparticles across sub-bronchial epithelial Calu-3 cells was also studied. In comparison with other methods of depositing microparticles, this proposed method, using drug suspended in HPFP, provides control over the amount of drugs applied on the surface of the cells. Therefore, cell permeability studies could be conducted with considerably smaller and more reproducible doses, without the physicochemical characteristics of the drugs being compromised or the use of modified pharmacopeia impactors. The suspension of microparticles in HPFP as presented in this study has provided a non-toxic, simple, and reproducible novel method to deliver and study the permeability of specific quantity of drugs across respiratory epithelial cells in vitro.

Free-radical sensing by using naphthalimide based mesoporous silica (MCM-41) nanoparticles: A combined fluorescence and cellular imaging study

Keeping in mind the advantages of material-based systems over simple molecule-based systems, we have designed and developed three inorganic-organic hybrid systems by anchoring 1,8-naphthalimide derivatives to mesoporous silica nanoparticles for detection of free radicals. Prior to photophysical study, systems are characterized by spectroscopic, microscopic and thermo-gravimetric techniques. Steady state and time-resolved fluorescence studies demonstrate that the hydrazine based system is senstive towards detection of various free radicals. Cellular imaging study reveals cell permeability and toxicity study demonstrates the non-toxic nature of the material. These studies have suggested that present system has the potential to be used in various biological applications.

Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor.

Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling by tyrosine dephosphorylation of the insulin receptor. It is a highly validated target for type 2 diabetes therapeutics. Here, the anti-diabetic effects of HPN were evaluated in the diabetic BKS db mice. The mode of inhibition of PTP1B by HPN was determined according to the Lineweaver-Burk plot. A surface plasmon resonance assay and molecular docking were used to study the interaction between HPN and PTP1B. C2C12 skeletal muscle cells were used to investigate the cell permeability of HPN and the effect of HPN on insulin signalling pathways. Long-term effects of HPN on glycaemic control were investigated in diabetic BKS db mice. Glycogen contents in liver and muscle were determined. Furthermore, changes in the number of beta cells were evaluated by Gomori staining. HPN was identified as a specific PTP1B inhibitor. HPN directly interacted with PTP1B by binding to the catalytic domain through hydrogen bonds in a competitive mode. Approximately 56.98% of HPN entered into the cultured C2C12 myotubes. HPN ameliorated the impaired insulin signalling in palmitate-treated C2C12 myocytes. Notably, oral administration of HPN significantly protected mice from hyperglycaemia, dyslipidemia and hyperinsulinaemia. HPN also enhanced the storage of glycogen in liver and muscle. Moreover, HPN obviously improved the beta cell numbers of the pancreatic islets. Our results indicate that HPN is a specific PTP1B inhibitor, with anti-diabetic properties and good cell permeability and oral availability.