Evaluation of the effect of carrier material on modification of release characteristics of poor water soluble drug from liquisolid compacts.

Liquisolid compact is a novel dosage form in which a liquid medication (liquid drug, drug solution/dispersion in non-volatile solvent/solvent system) is converted to a dry, free flowing powder and compressed. Objective of the study was to elucidate the effect of carrier material on release characteristics of clopidogrel from liquisolid compacts. Different formulations of liquisolid compacts were developed using microcrystalline cellulose, starch maize, polyvinyl pyrollidone and hydroxypropyl methylcellulose as carrier material in three concentrations (40, 30 and 20%, w/w). Liquid vehicle was selected on the basis of solubility of clopidogrel. Colloidal silicondioxide was used as coating material and ratio of carrier to coating material was kept 10. A control formulation comprised of microcrystalline cellulose (diluents), tabletose-80 (diluents), primojel (disintegrant) and magnesium stearate (lubricant) was prepared by direct compression technique and was used for comparison. All the formulations were evaluated at pre and post compression level. Acid solubility profile showed higher solubility in HCl buffer pH2 (296.89±3.49 µg/mL). Mixture of propylene glycol and water (2:1, v/v) was selected as liquid vehicle. Drug content was in the range of 99-101% of the claimed quantity. All the formulations showed better mechanical strength and their friability was within the official limits (<1%). Microcrystalline cellulose and starch maize resulted in faster drug release while polyvinyl pyrollidone and HPMC resulted in sustaining drug release by gel formation. It is concluded from results that both fast release and sustained release of clopidogrel can be achieved by proper selection of carrier material.

Exploring Charged Polymeric Cyclodextrins for Biomedical Applications.

Over the years, cyclodextrin uses have been widely reviewed and their proprieties provide a very attractive approach in different biomedical applications. Cyclodextrins, due to their characteristics, are used to transport drugs and have also been studied as molecular chaperones with potential application in protein misfolding diseases. In this study, we designed cyclodextrin polymers containing different contents of ß- or γ-cyclodextrin, and a different number of guanidinium positive charges. This allowed exploration of the influence of the charge in delivering a drug and the effect in the protein anti-aggregant ability. The polymers inhibit Amiloid ß peptide aggregation; such an ability is modulated by both the type of CyD cavity and the number of charges. We also explored the effect of the new polymers as drug carriers. We tested the Doxorubicin toxicity in different cell lines, A2780, A549, MDA-MB-231 in the presence of the polymers. Data show that the polymers based on γ-cyclodextrin modified the cytotoxicity of doxorubicin in the A2780 cell line.

Hydroxyethyl cellulose hydrogel for skin delivery of khellin loaded in ascosomes: Characterization, in vitro/in vivo performance and acute toxicity.

Aim of this work was to prepare and characterize a hydroxyethyl cellulose hydrogel loaded with ascosomes, nanovesicles based on phosphatidylcholine plus ascorbyl octanoate (ASC8) or ascorbyl decanoate (ASC1), and khellin (2 mg/mL), for topical use. ASC10 vesicles were selected for the hydrogel formulation because of the best biopharmaceutical characteristics, namely size of 115 nm, PDI of 0.26, ζ-potential of -40.1 meV, EE% of 90.2%. After 24 h the in vitro release of khellin was more than 80%, while the ex-vivo skin permeation of khellin after application of the vesicles was 42% of the dose. The hydrogel formulations had a pH value of 5, viscosity properties were different according to the different temperatures and in addition, they presented characteristics of non-Newtonian fluids with a pseudoplastic shear thinning behaviour according to the Herschel-Bulkley equation. These hydrogels combine the advantages of a suitable viscosity for dermal use (hydrogel matrix) and an increased transdermal absorption (ascosome components). The best permeability of the ASC10 ascosomes, led to select the formulation for skin irritation and corrosion tests in rats. Liver and dermal histological and pathological analyses demonstrated that hydroxyethyl cellulose hydrogels based on khellin loaded in the ASC10 ascosomes have no toxic effects.

Fibrillar pharmacology of functionalized nanocellulose.

Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

Analysis of kinetic parameters and mechanisms of nanocrystalline cellulose inhibition of α-amylase and α-glucosidase in simulated digestion of starch.

This study evaluated the in vitro inhibitory influence of particle size of nanocrystalline cellulose (NCC) fractions against α-amylase and α-glucosidase using cooked potato starch-protein food model system. The kinetics of the resulting inhibitions in the presence of NCC of the two tested enzymes were examined and characterised. Both the size and dose of NCC significantly (p < 0.05) inhibited α-amylase and α-glucosidase by modulating the rate of hydrolysis of starch in the food model system lower than that of the control (no added fibre). At equal concentrations of each NCC fraction, the smallest particle size (≤125 nm) exhibited the highest potency as an inhibitor (median inhibitory concentration (IC50) = 2.98 mg mL-1 and 4.57 mg mL-1 for α-amylase and α-glucosidase, respectively). Increasing concentrations of each NCC fraction caused an apparent significant decrease in Vmax values (p < 0.05) with insignificant change in the Km values for both the tested enzymes. Furthermore, binding assays demonstrated that NCC particles may bind to the two tested enzymes in a non-specific manner. Analysis of the kinetics of the enzymes suggested that the mechanism of inhibition showed that the two tested enzymes mainly exhibited non-competitive mode of inhibition. The observed inhibition of the two tested enzymes suggests that reducing the cellulose size ≤125 nm may enhance its inhibition potency and potentially attenuate starch hydrolysis when added to diet.

Bacterial nanocellulose as novel carrier for intestinal epithelial cells in drug delivery studies.

Synthetic cell carriers (A) represent common scaffold structures for the development of cell-based in vitro models of the human intestine but due to their low porosity or unwanted molecular adhesion effects, synthetic carriers can negatively affect cell function. Alternative scaffolds such as natural extracellular matrices (ECMs) (B) were shown to overcome some of the common drawbacks. However, their fabrication is time-consuming, less well standardized and not entirely conform to the 3R principle (replacement, reduction, refinement). Nowadays, biopolymers such as bacterial nanocellulose (BNC) (C) represent interesting scaffold materials for innovative tissue engineering concepts, as they can be generated in a faster and more standardized process workflow without the need for animal material. In this study, we demonstrate the BNC as suitable carrier for the development of Caco-2-based in vitro models of the human intestine. The BNC-based models exhibit organ-specific properties comprising typical cellular morphologies, characteristic protein expression profiles, representative ultrastructural features and the formation of a tight epithelial barrier. The proof of in vivo-like transport activities further validates the high quality of the BNC-based Caco-2 models. In summary, this illustrates the BNC as alternative bioscaffold of non-animal origin to develop functional organ models in vitro.

Pickering stabilized nanocellulose-alginate: A diosgenin-mediated delivery of quinalizarin as a potent cyto-inhibitor in human lung/breast cancer cell lines.

The current study explores the facile fabrication of multilayer self-assembled electrostatic oil-in-water Pickering emulsions (PEs) using quaternized nanocellulose (Q-NC) and diosgenin-conjugate alginate (DGN-ALG) particles as stabilizers to form hydrocolloid nanocarriers. The conditions of formulation such as storage time, pH, temperature and salt effect on the emulsion stability were evaluated. The results deduced showed good emulsion droplet stability over a period of 30 days. Morphological analysis revealed the hydrodynamic sizes of the PE droplets to be spherically shaped with an average diameter of 150 ± 3.51 nm. Creaming index, wettability and critical aggregation concentrations (CAC) as well as chemical characterization of the PEs were examined. In vitro release kinetics of encapsulated quinalizarin as a model drug was investigated with a determined cumulative drug release (CDR) of 89 ± 1.21% in simulated pH blood medium of pH 7.4. In addition, cellular internalization of the PEs was studied via confocal microscopy imaging and showed high cellular uptake. Also, evaluated in vitro cytotoxicity by MTT assay demonstrated excellent anticancer activity in human lung (A549) and breast (MCF-7) cancer cell lines.

Use of cellulose acetate butyrate as a carrier for preparation of alcohol-resistant matrix tablet.

The objective of this study was to investigate cellulose acetate butyrate (CAB) as a carrier for extended-release alcohol-resistant matrix tablet. Powder blends were either directly compressed or granulated before compression. The drug release from CAB matrix tablet was robust to formulation/process parameters such as compression force (10-20 kN), granular size (0.15-1.40 mm), and drug content (50-70%). In addition, release medium variables such as ionic strength, pH, and agitation rate had no effect on the drug release. CAB matrix tablet was more robust than ethylcellulose matrix tablet; the release from CAB matrix tablet was not affected by ethanol content (up to 20% v/v) in the release medium irrespective of agitation. CAB is a promising polymer for formulating of alcohol-resistant extended-release matrix tablet.

Water-dispersible, biocompatible and fluorescent poly(ethylene glycol)-grafted cellulose nanocrystals.

Fluorescent nanoprobe with good water dispersibility was synthesized by the coupling of fluorescent 1,8-naphthalimide dye (NANI) as well as biocompatible poly (ethylene glycol) (PEG) to cellulose nanocrystals (CNC). FTIR, TGA and XPS analysis confirmed the successful covalent conjugation of NANI and PEG. The rod-like morphology of CNC was generally retained after two-step successive grafting of NANI and PEG. The contact angle and transmittance measurements showed that the grafted PEG brushes improve the hydrophilicity of fluorescent CNC probes and their dispersibility in high-concentration NaCl solutions. The fluorescent CNC probe had good biocompatibility and was successfully used for the bioimaging of Hela cells in physiological environment at high salt concentration. Laser confocal microscopy showed that the fluorescent CNC probe can penetrate the cell membrane and disperse uniformly in the cell with good biocompatibility. The fluorescent CNC probe with nanometer size, strong fluorescence emission and high salt-tolerance possess potential application in biomedical field.

Synthesis, 99mTc-radiolabeling, and biodistribution of new cellulose nanocrystals from Dorema kopetdaghens.

Cellulose nanocrystals (CNCs) are known as nano-biomaterials that can be achieved from the different sources. The designated CNCs have been successfully fabricated from the roots of Dorema kopetdaghens (Dk) plant by sulphuric acid hydrolysis method. Structural analysis has been carried out by the means of XRD, FTIR, and TGA/DTG procedures. The XRD results have indicated that the crystalline structure of CNCs had been cellulose I with the crystallinity index of 83.20% and size of 4.95 nm. The FTIR spectra have shown that the resulting samples have been related to the cellulose species. The thermal properties of CNCs have exhibited a lower thermal stability in comparison to the untreated roots. It has been indicated by the morphological analyses of FESEM, TEM, and AFM that the nanoparticles had contained a spherical shape. Also, the cytotoxicity of CNCs against A549 cell line has not exhibited any cytotoxic effects. The analysis of labeling efficiency in regards to 99mTc-CNCs has been observed to be above 98%, while the biodistribution of radioactivity has displayed a high uptake by the kidneys and blood circulation. Therefore, it is possible to transform the low-cost by-product into a beneficial substance such as CNCs that can be utilized in bioimaging applications.

Systematic in vitro biocompatibility studies of multimodal cellulose nanocrystal and lignin nanoparticles.

Natural biopolymer nanoparticles (NPs), including nanocrystalline cellulose (CNC) and lignin, have shown potential as scaffolds for targeted drug delivery systems due to their wide availability, cost-efficient preparation, and anticipated biocompatibility. As both CNC and lignin can potentially cause complications in cell viability assays because of their ability to scatter the emitted light and absorb the assay reagents, we investigated the response of bioluminescent (CellTiter-Glo®), colorimetric (MTT® and AlamarBlue®), and fluorometric (LIVE/DEAD®) assays for the determination of the biocompatibility of the multimodal CNC and lignin constructs in murine RAW 264.7 macrophages and 4T1 breast adenocarcinoma cell lines. Here, we have developed multimodal CNC and lignin NPs harboring the radiometal chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and the fluorescent dye cyanine 5 for the investigation of nanomaterial biodistribution in vivo with nuclear and optical imaging, which were then used as the model CNC and lignin nanosystems in the cell viability assay comparison. CellTiter-Glo® based on the detection of ATP-dependent luminescence in viable cells revealed to be the best assay for both nanoconstructs for its robust linear response to increasing NP concentration and lack of interference from either of the NP types. Both multimodal CNC and lignin NPs displayed low cytotoxicity and favorable interactions with the cell lines, suggesting that they are good candidates for nanosystem development for targeted drug delivery in breast cancer and for theranostic applications. Our results provide useful guidance for cell viability assay compatibility for CNC and lignin NPs and facilitate the future translation of the materials for in vivo applications.

Multimodality labeling strategies for the investigation of nanocrystalline cellulose biodistribution in a mouse model of breast cancer.

METHODS: We have developed a nuclear and fluorescence labeling strategy for nanocrystalline cellulose (CNC), an emerging biomaterial with versatile chemistry and facile preparation from renewable sources. We modified CNC through 1,1'-carbonyldiimidazole (CDI) activation with radiometal chelators desferrioxamine B and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), allowing for the labeling with zirconium-89 (t½â€¯= 78.41 h) and copper-64 (t½â€¯= 12.70 h), respectively, for non-invasive positron emission tomography (PET) imaging. The far-red fluorescent dye Cy5 was added for ex vivo optical imaging, microscopy and flow cytometry. The multimodal CNC were evaluated in the syngeneic orthotopic 4T1 tumor model of human stage IV breast cancer. RESULTS: Modified CNC exhibited low cytotoxicity in RAW 264.7 macrophages over 96 h, and high radiolabel stability in vitro. After systemic administration, radiolabeled CNC were rapidly sequestered to the organs of the reticulo-endothelial system (RES), indicating immune recognition and no passive tumor targeting by the enhanced permeability and retention (EPR) effect. Modification with NOTA was a more favorable strategy in terms of radiolabeling yield, specific radioactivity, and both the radiolabel and dispersion stability in physiological conditions. Flow cytometry analysis of Cy5-positive immune cells from the spleen and tumor corroborated the uptake of CNC to phagocytic cells. CONCLUSIONS: Future studies on the in vivo behavior of CNC should be concentrated on improving the nanomaterial stability and circulation half-life under physiological conditions and optimizing further the labeling yields for the multimodality imaging strategy presented. ADVANCES IN KNOWLEDGE: Our studies constitute one of the first accounts of a multimodality nuclear and fluorescent probe for the evaluation of CNC biodistribution in vivo and outline the pitfalls in radiometal labeling strategies for future evaluation of targeted CNC-based drug delivery systems. IMPLICATIONS FOR PATIENT CARE: Quantitative and sensitive molecular imaging methods provide information on the structure-activity relationships of the nanomaterial and guide the translation from in vitro models to clinically relevant animal models.

The role of viscosity on skin penetration from cellulose ether-based hydrogels.

BACKGROUND: The rheological properties of dermal drug delivery systems are of importance when designing new formulations. Viscosity not only affects features such as spreadability and skin feel, but may also affect the skin penetration of incorporated actives. Data on the latter aspect are controversial. Our objective was to elucidate the relation between viscosity and drug delivery performance of different model hydrogels assuming that enhanced microviscosity might delay drug release and penetration. MATERIALS AND METHODS: Hydrogels covering a broad viscosity range were prepared by adding either HPMC or HEC as gelling agents in different concentrations. To investigate the ability of the gels to deliver a model drug into the skin, sulphadiazine sodium was incorporated and its in vitro skin penetration was monitored using tape stripping/HPLC analysis and non-invasive confocal Raman spectroscopy. RESULTS: The trends observed with the two different experimental setups were comparable. Drug penetration depths decreased slightly with increasing viscosity, suggesting slower drug release due to the increasingly dense gel networks. However, the total penetrated drug amounts were independent of the exact formulation viscosity. CONCLUSION: Drug penetration was largely unaffected by hydrogel viscosity. Moderately enhanced viscosity is advisable when designing cellulose ether hydrogels to allow for convenient application.

Formulation of Ethyl Cellulose Microparticles Incorporated Pheophytin A Isolated from Suaeda vermiculata for Antioxidant and Cytotoxic Activities.

BACKGROUND: This study is designed to discover a method for delivering an efficient potent pheophytin a (pheo-a) into more absorbed and small polymeric ethyl cellulose (EC) microparticles. METHODS: Silica gel and Sephadex LH-20 columns were used to isolate pheo-a from the chloroform extract of the edible plant, Suaeda vermiculata. Pheo-a was incorporated into EC microparticles using emulsion-solvent techniques. The antioxidant activity of pheo-a microparticles was confirmed by the level of superoxide radical (SOD), nitric oxide (NO), and reducing power (RP) methods. Meanwhile, the cytotoxic effect of the product was investigated on MCF-7 cells using MTT assay. RESULTS: Pheo-a was isolated from S. vermiculata in a 12% concentration of the total chloroform extract. The structures were confirmed by NMR and IR spectroscopic analysis. The formulated microparticles were uniform, completely dispersed in the aqueous media, compatible as ingredients, and had a mean diameter of 139 ± 1.56 µm as measured by a particle size analyzer. Pheo-a demonstrated a valuable antioxidant activity when compared with ascorbic acid. The IC50 values of pheo-a microparticles were 200.5 and 137.7 µg/mL for SOD, and NO respectively. The reducing power of pheo-a microparticles was more potent than ascorbic acid and had a 4.2 µg/mL for IC50 value. Pheo-a microparticles did not show notable cytotoxicity on the MCF-7 cell line (IC50 = 35.9 µg/mL) compared with doxorubicin (IC50 = 3.2 µg/mL). CONCLUSIONS: the results showed that water-soluble pheo-a microparticles were prepared with a valuable antioxidant activity in a wide range of concentrations with a noteworthy cytotoxic effect.

Preparation and Characterization of Cellulose Ether Liposomes for the Inhibition of Prion Formation in Prion-Infected Cells.

Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC50 dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prion-infected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action.

Selectively Oxidized Cellulose with Adjustable Molecular Weight for Controlled Release of Platinum Anticancer Drugs.

The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.

Magnetic cellulose nanocrystal stabilized Pickering emulsions for enhanced bioactive release and human colon cancer therapy.

Stimuli-responsive drug release and controlled delivery play crucial roles in enhancing the therapeutic efficacy and lowering over-dosage induced side effects. In this paper, we report magnetically-triggered drug release and in-vitro anti-colon cancer efficacy of Fe3O4@cellulose nanocrystal (MCNC)-stabilized Pickering emulsions containing curcumin (CUR). The loading efficiency of CUR in the micron-sized (≈7 µm) MCNC-stabilized Pickering emulsions (MCNC-PE) template was found to be 99.35%. The drug release profiles showed that the exposure of MCNC-PE to external magnetic field (EMF) (0.7 T) stimulated the release of bioactive from MCNC-PE achieving 53.30 ±â€¯5.08% of the initial loading over a 4-day period. The MTT assay demonstrated that the CUR-loaded MCNC-PE can effectively inhibits the human colon cancer cells growth down to 18% in the presence of EMF. The formulation also resulted in 2-fold reduction on the volume of the 3-D multicellular spheroids of HCT116 as compared to the control sample. The MCNC particle was found to be non-toxic to brine shrimp up to a concentration of 100 µg/mL. Our findings suggested that the palm-based MCNC-PE could be a promising yet effective colloidal drug delivery system for magnetic-triggered release of bioactive and therapeutics.

Dynamic rheology as a quantitative method for real-time tracking of excipient solvation in non-aqueous hydroxypropylcellulose topical gels.

This article describes a method to quantitatively track the solvation of HPC in a non-aqueous solvent system during topical gel manufacture. Where visual observation and microscopy could not establish a trend, straight-forward rheological profiling demonstrated a correlation between increased solvation of hydroxypropyl cellulose polymer (viscosity modifier) and decreased tan δ, indicating the formation of a viscoelastic gel network over time during processing. This correlation serves as a valuable tool for process optimization and HPC solvation tracking in non-aqueous topical gel formulations.

Pickering emulsions stabilized nanocellulosic-based nanoparticles for coumarin and curcumin nanoencapsulations: In vitro release, anticancer and antimicrobial activities.

Coumarin and curcumin have a wide spectrum of biological and pharmacological activities including antioxidant, anti-inflammatory, antimicrobial and anticancer but hindered therapeutic applications due to low stability and poor solubility in water. The main objective of the current study was to overcome these drawbacks via improved bioavailability by nanoencapsulated emulsions. Pickering emulsion (PE) via oil-in-water approach were stabilized by aminated nanocellulose (ANC) particles through application of a full factorial optimization design for nanoemulsions containing different composition of oil phase with medium chain triglyceride (MCT) and Tween 80. The fabricated nanoemulsions and PEs with average particle sizes (≤150 nm) were obtained. Influencing factors such as ANC concentration, storage time and pH on the stability of emulsions were examined alongside zeta potentials. Encapsulation efficiency (EE) of coumarin and curcumin were determined as >90%. Release kinetic profiles for encapsulated PEs displayed sustained release with supposed increase bioavailability. Higher release percent were detected for curcumin encapsulated PE in contrast to coumarin. In vitro cytotoxicity evaluation for coumarin and curcumin loaded PEs were further investigated for anticancer and antimicrobial activities using human cell lines (L929 and MCF-7) and different microorganisms (Gram (+), Gram (-) and fungi), respectively. The results clearly demonstrated PE coumarin and curcumin as promising candidates to inhibit microbial growth and to prevent preferential killing of cancer cells compared to normal cells.

Physicochemical and biopharmaceutical characterization of celecoxib nanoparticle: Avoidance of delayed oral absorption caused by impaired gastric motility.

The present study aimed to develop a celecoxib (CEL) nanoparticle with improved dissolution/dispersion and consistent absorption even in the presence of impaired gastric motility. CEL was pulverized by a wet-milling with hydroxypropyl cellulose (HPC), and the prepared nanoparticles were physicochemically characterized after freeze-drying. CEL nanoparticle with HPC-SSL (NP/CEL) exhibited better dissolution/dispersion behavior in pH1.2 solution compared with CEL nanoparticles with other polymers, as evidenced by a 21.8-fold higher initial dissolution/dispersion rate than crystalline CEL. The mean particle diameter of water suspended-NP/CEL was 250 nm, and the CEL nanoparticle existed in an amorphous state. Even after storage at 40 °C for 4 weeks, there were no significant changes in the dissolution/dispersion behavior. Oral absorption of CEL samples (5 mg-CEL/kg) was evaluated in normal and propantheline (PPT)-treated rats with simulated gastric motility impairment. In PPT-treated rats, oral crystalline CEL led to a decrease in oral absorption by 12% of the AUC0-4 compared with that in normal rats, whereas NP/CEL suppressed the pharmacokinetic transition of CEL by 43% of the AUC0-4 due to the improved dissolution/dispersion behavior of CEL. The NP/CEL system might be promising to avoid decreased absorption of CEL caused by impaired gastric motility.