Engineered microparticles based on drug–polymer coprecipitates for ocular-controlled delivery of Ciprofloxacin: influence of technological parameters

Abstract

Ciprofloxacin is a drug active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria, for the therapy of ocular infections. It requires frequent administrations owing to rapid ocular clearance and it is a good candidate for ocular controlled release formulations. The preparation of such drug release systems is still a challenge. Ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan result in coprecipitates that can act as microparticulate controlled release systems from which the drug is released after being displaced by the medium’s ions. In some formulations, Carbopol was added to improve the mucoadhesive properties. The aim of this research was the study of the influence of the technological parameters of the preparation method of coprecipitates on their particle size, with the goal of achieving particles engineered with a size suitable for the ocular administration. Technological parameters taken into account were: concentration of drug and polymer solutions utilized for the preparation of interaction products, possible use of surfactants (kind and concentration), temperature of the solutions and stirring during the process of preparation of the coprecipitates. Preliminary stability study tests were carried out to further characterize the leader formulation. Particle size in suspensions for ocular drug delivery is a critical parameter influencing the quality of the formulation. The results obtained from this study show that chondroitin sulfate coprecipitates present the best characteristics in terms of particle size suitable for ocular administration. A further improvement of the particle size characteristics has been obtained with the addition of surfactants.     

In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery

The development of smart targeted nanoparticle that can deliver drugs to direct cancer cells, introduces better efficacy and lower toxicity for treatment. We report the development and characterizations of pH-sensitive carboxymethyl chitosan modified folic acid nanoparticles and manifest their feasibility as an effective targeted drug delivery vehicle. The nanoparticles have been synthesized from carboxymethyl chitosan with covalently bonded bifunctional 2,2′-(ethylenedioxy)-bis-(ethylamine) (EDBE) through the conjugation with folic acid. The conjugation has been analyzed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The resultant nanoparticles with an average size less then 200 nm measured by dynamic light scattering and transmission electron microscopy. Confocal microscopy and flow cytometric analysis have revealed that folate-mediated targeting significantly enhances the cellular uptake of the nanoparticle and thus facilitates apoptosis of cancer cells (HeLa, B16F1). For the application of the nanoparticles as a drug carrier, Doxorubicin a potent anticancer drug has been loaded into the nanoparticles, with the drug loading amount and the drug release pattern observed.     

In vitro and in vivo evaluation of chitosan–gelatin scaffolds for cartilage tissue engineering

Chitosan–gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan–gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1_WSC) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1_WSC promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5 months. The amount of glycosaminoglycans in C1G1_WSC constructs (0.187 ± 0.095 μg/mg tissue) harvested from the animals after 6.5 months was 14 wt.% of that in normal cartilage (1.329 ± 0.660 μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5 months was about 0.539 MPa, which approached to that of normal cartilage (0.735 MPa), while that in the blank control (3.881 MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1_WSC constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1_WSC scaffolds may enhance the cartilage regeneration in vitro and in vivo.     

PLGA–PEG–PLGA hydrogel for ocular drug delivery of dexamethasone acetate

Aim: This study aims to investigate the suitability of thermosensitive triblock polymer poly-(dl-lactic acid-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). Methods: The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA–PEG–PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. Result: The copolymer with 20% (w/w) had a low critical solution temperature of 32°C, which is close to the surface temperature of the eye. The C_max of DXA in the anterior chamber for the PLGA–PEG–PLGA solution was 125.2 μg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration–time curves (AUC). Conclusion: These results suggest that the PLGA–PEG–PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.     

Development and in vitro–in vivo evaluation of a water-in-oil microemulsion formulation for the oral delivery of troxerutin

Objective: The main objective of this study was to develop and evaluate a W/O microemulsion formulation of troxerutin to improve its oral bioavailability.

Methods: The W/O microemulsion was optimized using a pseudo-ternary phase diagram and evaluated for physical properties. In vitro MDCK cell permeability studies were carried out to evaluate the permeability enhancement effect of microemulsion, and in vivo absorption of troxerutin microemulsion in the intestine was compared with that of solution after single-dose administration (56.7?mg/kg) in male Wistar rats.

Results: The optimal formulation consisted of lecithin, ethanol, isopropyl myristate and water (23.30/11.67/52.45/12.59 w/w) was physicochemical stable and the mean droplet size was about 50.20?nm. In vitro study, the troxerutin-loaded microemulsion showed higher intestinal membrane permeability across MDCK monolayer when compared with the control solution. The W/O microemulsion can significantly promote the intestinal absorption of troxerutin in rats in vivo, and the relative bioavailability of the microemulsion was about 205.55% compared to control solution.

Conclusion: These results suggest that novel W/O microemulsion could be used as an effective formulation for improving the oral bioavailability of troxerutin.     

In vitro evaluation of human osteoblast adhesion to a thermally oxidized γ-TiAl intermetallic alloy of composition Ti–48Al–2Cr–2Nb (at.%)

Ti–48Al–2Cr–2Nb (at.%) (γ-TiAl), a gamma titanium aluminide alloy originally designed for aerospace applications, appears to have excellent potential as implant material. Thermal treatment of γ-TiAl renders this alloy extremely corrosion resistant in vitro, which could improve its biocompatibility. In this study, the surface oxides produced by thermal oxidation (at 500°C, and at 800°C for 1 h in air) on γ-TiAl were characterized by X-ray photoelectron spectroscopy (XPS). hFOB 1.19 cell adhesion on thermally oxidized γ-TiAl was examined in vitro by a hexosaminidase assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) after 1, 7 and 14 days. Ti–6Al–4V surfaces were used for comparison. Hexosaminidase assay data and CLSM analysis of focal contacts and cytoskeleton organization showed no differences in cell attachment on autoclaved and both heat-treated γ-TiAl surfaces at the different time points. SEM images showed well organized multi-layers of differentiated cells adhered on thermally oxidized γ-TiAl surfaces at day 14. Unexpectedly, thermally oxidized Ti–6Al–4V surfaces oxidized at 800°C exhibited cytotoxic effects on hFOB 1.19 cells. Our results indicate that thermal oxidation of γ-TiAl seems to be a promising method to generate highly corrosion resistant and biocompatible surfaces for implant applications.     

In vitro release dynamics of model drugs from psyllium and acrylic acid based hydrogels for the use in colon specific drug delivery

Psyllium is medicinally important gel forming polysaccharides. Keeping in view, the pharmacological importance of psyllium and drug delivery devices based on hydrogels, psyllium, if suitably tailored to prepare the hydrogels, can act as the double potential candidates for the novel drug delivery systems. Therefore, it is an attempt to prepared psyllium and acrylic acid based pH sensitive novel hydrogels by using N,N'-methylenebisacrylamide (N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator for the use in colon specific drug delivery. The present paper discusses the swelling kinetics of the hydrogels and release dynamics of model drugs (tetracycline hydrochloride, insulin and tyrosine) from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the polymeric networks .The effect of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable.     

In vitro studies of novel CaO–SiO2–MgO system composite bioceramics

In this study, a series of CaO–SiO₂–MgO composites with different β-CaSiO₃ (CS)/Mg₂SiO₄ (M₂S) composite ratios were prepared to produce new bioactive and biodegradable biomaterials for potential bone repair. The mechanical properties of CS–M₂S composites increased steadily with the increase of M₂S ratios in composites. Dissolution tests in Tris–HCl buffer solution showed obvious differences with different CS initial composite ratio in composites. The dissolution rate increased with the increase of CS composite ratio, which suggested that the solubility of composites could be tailored by adjusting the initial CS/M₂S composite ratio. Formation of bone-like apatite on a range of CS–M₂S composites with CS weight percentage ranging from 0 to 100 has been investigated in simulated body fluid (SBF). The presence of bone-like apatite layer on the composite surface after soaking in SBF was demonstrated by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM). The results showed that the apatite formation ability of the CS–M₂S composite with 70% CS was detected after 10 days immersion. In vitro cell experiments showed that the 50 and 70% CS composites supported greater osteoblast-like cell proliferation as compared with pure M₂S (p < 0.05). The results of this study suggested that the CS–M₂S composites with 50 and 70% initial CS composite amount might be more suitable for preparation of bone repair materials.     

Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization,in vitro and in vivo evaluation

Purpose: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (～30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box–Behnken design (BBD) to improve the oral bioavailability.

Methods: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A₁), amount of surfactant (A₂) and concentration of co-surfactant (%) (A₃) were selected as independent variables, whereas, particle size (B₁), entrapment efficiency (B₂) and zeta potential (ZP, B₃) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.

Results: The optimized formulation with 132.89?mg of lipid, 106.7?mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9?±?3.7?nm of size, ?25.66?±?2.83?mV surface charge and 86.83?±?2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.

Conclusions: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.     

Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery

New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo(2) cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.     

Acrylic acid–methyl methacrylate (2.5:7.5/2:8) enteric copolymer for colon targeted drug delivery

Enteric copolymers of acrylic acid and methyl methacrylate (2.5:7.5 and 2:8) were prepared using tetrahydrofuran as solvent and AIBN as free radical initiator for colon targeting. FTIR and ¹H NMR spectra of the copolymers showed absence of vinyl bond/protons present in the monomers suggesting successful polymerization. Flurbiprofen sodium microspheres (M1 and M2) made with the copolymers, by oil/oil solvent evaporation, were spherical, anionic (zeta potential –57.8 and –53.7 mV) and contained 5.47 and 5.89% drug. FTIR spectrum of microspheres showed peaks for aromatic C = C stretching and substituted benzene ring, indicating entrapment of flurbiprofen. PXRD revealed crystalline structure of flurbiprofen while copolymer and microspheres were amorphous. DSC thermograms showed a sharp melting endotherm of flurbiprofen sodium at 129.26°C against broad endotherms of copolymers and microspheres. The microspheres released 43 and 36% drug at pH 6.8 in 2 h and 99 and 96% at pH 7.4 in next 3–4 h.The microspheres did not adhere on gastric-mucosa at pH 1.2 but showed mucoadhesion time of 18 min and 9 min on intestinal mucosa at pH 6.8. Thus, the microspheres on oral administration, would release the drug in colon, suggesting the potential of the hemocompatible copolymers for pH dependent colon targeted drug delivery system.     

PEGylated nanostructured lipid carriers (PEG–NLC) as a novel drug delivery system for biochanin A

With the aim to develop a lipid nanoparticle for biochanin A (BCA) by emulsion-evaporation and low temperature-solidification technique. The results revealed that BCA–PEG–NLC not only have small mean particle (148.5?±?2.88?nm) with narrow polydispersity index (PI) (0.153?±?0.01), encapsulation capacity (99.62?±?0.06%), payload (9.06?±?0.01%), zeta potential (?19.83?±?1.19?mV), but also slower release rate compared with BCA suspension over 48?h by the dialysis method (n=3). The crystallinity of lipid matrix within BCA–PEG–NLC was evaluated by differential scanning calorimetry (DSC) which verified the BCA successfully into the nanoparticles. Particularly, in pharmacokinetic, the BCA–PEG–NLC of C_max values and AUC (area under curve) was higher than BCA suspension (approximately 15.8 and 2.9 times, respectively), meanwhile, the mean residence time (MRT) was significantly longer. Furthermore, in vitro cytotoxicity BCA–PEG–NLC showed higher cytotoxicity against MCF-7 cell line compared with BCA suspension. This study suggested that PEG–NLC is a novel anti-cancer nanoparticle, which could provide attractive treatment for a wide variety of tumors and improved the oral bioavailability of poorly water-soluble drug.     

Biocompatibility evaluation of a novel hydroxyapatite-polymer coating for medical implants (in vitro tests)

Nanocomposites consisting of hydroxyapatite (HA) and a sodium maleate copolymer (maleic polyelectrolyte), synthesized by hydrothermal method and deposited on titanium substrates by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique were tested for the biological properties. Coating bioanalysis was carried out by triple staining of actin, microtubules and nuclei followed by immunofluorescence microscopy. Within 24 h cells that occupied the biomaterial surface displayed the morphology and cytoskeleton pattern similar to the controls. Cells grown on nanocomposite coated surfaces had a higher proliferation rate than their counterparts grown on Ti coated with HA alone, indicating that maleic polyelectrolyte improved surface bio-adhesive characteristics. The capacity to induce cell attachment, spreading and proliferation demonstrated the potential of Ti coated with HA-polymer nanocomposites to be used as scaffolds in dental or orthopedic implantology.     

Preparation and characterization of self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin using hydrophobic complexation by cationic polymer of β-cyclodextrin

Objective: The aim of this study was the preparation of a self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin.

Significance: Preparation of hydrophobic complexes between heparin as the hydrophilic macromolecule and cationic polymer of β-cyclodextrin (CPβCD) was considered for preparation of orally administered SNEDDS in which the drug incorporated in internal oil phase of O/W nano-droplets.

Methods: Hydrophobic complexes of heparin-CPβCD were prepared by electrostatic interaction. The lipophilic feature of complexes was characterized by determining their partition co-efficients. SNEDDS prototypes were prepared by mixing liquid paraffin, Tween 80, propylene glycol and ethanol, diluted 1:100 in an aqueous medium. Central composite response surface methodology was applied for statistical optimization. Independent variables were the amount of liquid paraffin and the amount of Tween 80, while responses were size and poly dispersity index (PdI). Optimized SNEDDS were studied morphologically using transmission electron microscopy (TEM). In vitro release of heparin was studied in the simulated gastric and simulated intestinal media.

Results: The data revealed that in molar ratio 1:3 (heparin:CPβCD), the n-octanol recovery was maximized and reached 67.6?±?11.86%. Size, PdI, zeta potential, EE% in gastric medium and EE% in intestinal medium for optimized nano-droplets were reported as 307?±?30.51?nm, 0.236?±?0.02,?+2.1?±?0.66?mV, 90.2?±?0.04 and 96.1?±?0.73%, respectively. Microscopic images revealed spherical nano-droplets. The obtained data revealed no burst release of heparin from nano-droplets.

Conclusions: The obtained results indicate that SNEDDS could be regarded as a good candidate for oral delivery of heparin as the hydrophilic macromolecule.     

Preparation of CuInSe2 thin films by selenization of co-sputtered Cu–In precursors

CuInSe2 thin films have been prepared by high Se vapor selenization of co-sputtered Cu–In alloy precursors within a partially closed graphite container. Cu–In alloys with different compositions were investigated. X-ray diffraction (XRD) analysis of the films showed mainly CuIn2 and Cu11In9 phases and the Cu11In9 peak intensity was found to increase as the alloy composition tended towards Cu-rich. A linear dependence of the alloy composition on the Cu/In deposition power was observed from energy dispersive analysis by X-rays (EDX). A three-fold volume expansion was exhibited by all the CuInSe2 films after selenization at 500–550 °C. Scanning electron microscopy (SEM) analysis of the films showed large and densely packed crystal structures with sizes above 5 m. The CuInSe2 films exhibited single phase chalcopyrite structure with preferential orientation in the (1 1 2) direction. The EDX composition analyses of the films showed Cu/In ratio ranging from 0.43 to 1.2, and Se/(Cu+In) ratios from 0.92 to 1.47. The measured film resistivities varied from 10-1 to 105 cm. The Cu–In alloy precursors with Cu/In ratio less than 0.70 were found to form CuIn3Se5 a defect chalcopyrite compound. All films were Se rich, with the exception of samples with very high Cu content.© 1998 Kluwer Academic Publishers     

Design,optimization and evaluation of poly-ɛ-caprolactone (PCL) based polymeric nanoparticles for oral delivery of lopinavir

Lopinavir (LPV)-loaded poly-ε-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box–Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3?nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV.     

CuInGaSe2 crystals synthesis by selenization of Cu–In–Ga alloy in H2Se atmosphere for solar cell applications

Copper indium gallium diselenide (CuInGaSe₂) crystals were synthesized using two step growth strategy. A facile solution route was employed as a primary step to synthesize Cu–In–Ga (CIG) metallic precursor using ethylenediamine as a solvent. Thin films of CIG metallic precursor have been deposited using spray deposition technique on to molybdenum coated soda lime glass substrate under inert atmosphere. The subsequent step involved the selenization of metallic precursor thin films in H₂Se atmosphere at 450 °C for 90 min followed by annealing in Ar thus yielding solar cell applicable dense CuInGaSe₂ crystals. The surface morphology, phase structure and composition of the deposited films were analyzed by field emission scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy and electrical resistivity measurement respectively. The results revealed that annealed films were crystalline in nature exhibiting homogeneous single chalcopyrite phase.     

In vitro behavior of human osteoblast-like cells (SaOS2) cultured on surface modified titanium and titanium–zirconium alloy

In this study, titanium (Ti) and titanium–zirconium (TiZr) alloy samples fabricated through powder metallurgy were surface modified by alkali-heat treatment and calcium (Ca)-ion-deposition. The alteration of the surface morphology and the chemistry of the Ti and TiZr after surface modification were examined. The bioactivity of the Ti and TiZr alloys after the surface modification was demonstrated. Subsequently, the cytocompatibility of the surface modified Ti and TiZr was evaluated via in vitro cell culture using human osteoblast-like cells (SaOS2). The cellular attachment, adhesion and proliferation after cell culture for 14 days were characterized by scanning electron microscopy (SEM) and MTT assay. The relationship between surface morphology and chemical composition of the surface modified Ti and TiZr and cellular responses was investigated. Results indicated that the surface-modified Ti and TiZr alloys exhibited excellent in vitro cytocompatibility together with satisfactory bioactivity. Since osteoblast adhesion and proliferation are essential prerequisites for a successful implant in vivo, these results provide evidence that Ti and TiZr alloys after appropriate surface modification are promising biomaterials for hard tissue replacement.     

In vitro stability study of organophosphonic self assembled monolayers (SAMs) on cobalt chromium (Co–Cr) alloy

Surface modification of cobalt chromium (Co–Cr) alloy is being investigated as a possible solution to the biomedical challenges arising from its usage. Self assembled monolayers (SAMs) of organophosphonic octadecylphosphonic acid (ODPA) were formed on the oxide surface of Co–Cr alloy by chemisorption using the solution deposition technique. High quality and well-ordered SAMs were formed which were characterized using Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), contact angle measurements and ellipsometry. The resulting monolayers were then exposed to in vitro conditions using phosphate buffered saline (PBS) solution. The samples were analyzed for a period of 1, 3, 7 and 14 days. The resulting samples were characterized using XPS, AFM and Contact angle measurements. XPS atomic concentrations and detailed high energy elemental scans gave an insight into the trends of elemental concentrations over the duration of the study. SAMs were found to be strongly bound to the oxide surface after PBS exposure. AFM gave the topographic details of SAMs presence by island formation before and after SAM formation and also over the duration of the PBS exposure. Contact Angle Measurements confirmed the hydrophobicity of the surface after SAM formation and indicated a slight disorder of the SAM alkyl chain upon exposure to PBS. Thus, ODPA SAMs were successfully coated on Cobalt Chromium (Co–Cr) alloy surface and were found to be stable and strongly bound after PBS exposure.     

In vitro activity of resorcinarene–chlorambucil conjugates for therapy in human chronic myelogenous leukemia cells

A possible way of improving the activity and selectivity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules. Thus, four resorcinarene-PAMAM-dendrimer conjugates of chlorambucil with different groups in the lower part of the macrocycle and different length dendritic arms showed a good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the resorcinarene-PAMAM-dendrimer–chlorambucil conjugate employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) demonstrated that the conjugate was more potent as an antiproliferative agent than chlorambucil.