Evaluation of the Trend of Biochemical Functions in the Early Period After Cadaveric Liver Transplantation.

BACKGROUND: Monitoring biochemical parameters to detect early complications after liver transplantation (LT) is important. Thus, we aimed to investigate parameter trends indicating liver function in patients who did not develop complications after cadaveric LT. METHODS: A total of 266 cadaveric LT operations performed by a single center between 2007-2022 were included in the study. Patients with any early complications were excluded from the study. During the first 15 days, the parameters reflecting the patients' liver integrity and synthesis functions were evaluated. All parameters studied were evaluated at the same time of day and by a single laboratory. RESULTS: Regarding synthesis functions, the coagulation parameters (prothrombin time and international normalized ratio) peaked on the first day and then decreased. Regarding tissue hypoxia, there was no significant change in lactate values. Total and direct bilirubin values also decreased after peaking on the first day. No significant change was observed in albumin, another liver synthesis value. CONCLUSIONS: Although an increase in aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, prothrombin time, and international normalized ratio, which was especially seen on the first day, is considered normal, values that do not decrease after the second day or lactate values that increase gradually should be a warning in terms of possible early complications.

Design and Characterization of Carboplatin and Paclitaxel Loaded PCL Filaments for 3D Printed Controlled Release Intrauterine Implants.

Uterine cancer is the fourth most common cancer in women. Despite various chemotherapy approaches, the desired effect has not yet been achieved. The main reason is each patient responds differently to standard treatment protocols. The production of personalized drugs and/or drug-loaded implants is not possible in today's pharmaceutical industry; 3D printers allow for the rapid and flexible preparation of personalized drug-loaded implants. However, the key point is the preparation of drug-loaded working material such as filament for 3D printers. In this study, two different anticancer (paclitaxel, carboplatin) drug-loaded PCL filaments with a 1.75 mm diameter were prepared with a hot-melt extruder. To optimize the filament for a 3D printer, different PCL Mn, cyclodextrins and different formulation parameters were tried, and a series of characterization studies of filaments were conducted. The encapsulation efficiency, drug release profile and in vitro cell culture studies have shown that 85% of loaded drugs retain their effectiveness, provide a controlled release for 10 days and cause a decrease in cell viability of over 60%. In conclusion, it is possible to prepare optimum dual anticancer drug-loaded filaments for FDM 3D printers. Drug-eluting personalized intra-uterine devices can be designed for the treatment of uterine cancer by using these filaments.

A different approach to immunochemotherapy for colon Cancer: Development of nanoplexes of cyclodextrins and Interleukin-2 loaded with 5-FU.

Immune system deficiencies are crucial in the progression of cancer, predominantly because immune cells are not stimulated by cytokines to eradicate cancer cells. Immunochemotherapy is currently considered an innovative approach that creates pathways in cancer treatment, sometimes also aiding in the efficacy of chemotherapeutics. The aim of this study was to prepare a cyclodextrin (CD) nanoplex based on charge interaction to deliver the anticancer drug 5-fluorouracil (5-FU) and Interleukin-2 (IL-2), thereby forming a nanoscale drug delivery system aimed at chemo-immunotherapy for colorectal cancers. The CD:IL-2 nanoplexes were obtained with a particle size below 100 nm and a cationic surface charge based on the extent of charge interaction of the cationic CD polymer with negatively charged IL-2. The loading capacity of CD nanoplexes was 40% for 5-FU and 99.8% for IL-2. Nanoplexes maintained physical stability in terms of particle size and zeta potential in aqueous solution for 1 week at + 4 °C. Moreover, the structural integrity of IL-2 loaded into CD nanoplexes was confirmed by SDS-PAGE analysis. The cumulative release rates of both 5-FU and IL-2 were found to be more than 80% in simulated biological fluids in 12 h. Cell culture studies demonstrate that CD polymers are safe on healthy L929 mouse fibroblast cells. Drug-loaded CD nanoplexes were determined to have a higher anticancer effect than free drug solution against CT26 mouse colon carcinoma cells. In addition, intestinal permeability studies supported the conclusion that CD nanoplexes could be promising candidates for oral chemotherapy as well. In conclusion, effective cancer therapy utilizing the absorptive/cellular uptake effect of CDs, the synergic effect and co-transport of chemotherapeutic drugs and immunotherapeutic molecules is a promising approach. Furthermore, the transport of IL-2 with this nano-sized system can reduce or avoid its toxicity problem in the clinic.

Regulation of chondrocyte hypertrophy in an osteochondral interface mimicking gel matrix.

Calcified cartilage extracellular matrix (ECM) is a critical interface at the osteochondral junction which plays an important role in maintaining the structural continuity between articular cartilage and subchondral bone. This mineralized network is primarily composed of glycosaminoglycans (GAGs) and collagen type II (col II) and hosts hypertrophic chondrocytes. This work aimed to investigate the effect of gel composition and collagen II content on the behavior and hypertrophic differentiation of ATDC5 cells for regeneration of calcified cartilage tissue. For this purpose, chitosan/collagen type II/nanohydroxyapatite (chi/col II/nHA) composite hydrogels were prepared to mimic the calcified cartilage ECM. ATDC5 cells were encapsulated within the composite gels and the viability, ECM production and hypertrophic gene expression were assessed during culture. All composites were favorable for ATDC5 viability and proliferation, whereas specific ECM production and hypertrophic differentiation were dependent on gel composition. Chitosan: collagen II ratio had an impact on ATDC5 cell fate. Hypertrophic differentiation was best pronounced in chi/col II/nHA 70:30 composition. The results obtained from this study offers a scaffold-based approach for calcified cartilage regeneration and provide an insight for biomimetic design and preparation of more complicated gradient osteochondral units.

Chitosan/collagen based biomimetic osteochondral tissue constructs: A growth factor-free approach.

Tissue engineering approach offers alternative strategies to develop multi-layered/multi-component osteochondral mimetic constructs to meet the requirements of the heterogeneous and layered structure of native osteochondral tissue. Herein, an iterative overlaying process to fabricate a multi-layered scaffold with a gradient composition and layer specific structure have been developed by combining the natural extracellular matrix (ECM) components-chitosan, type I collagen, type II collagen, nanohydroxyapatite- of the osteochondral tissue in biomimetic compositions. Subchondral bone layer was prepared by using freeze-drying method to obtain 3D porous scaffolds. The calcified cartilage and cartilage layers were prepared by thermal gelation method in the hydrogel form. Osteochondral scaffolds fabricated by iterative overlaying of each distinct layer exhibited a porous, continuous gradient structure and supported cell proliferation in a co-culture of MC3T3-E1 preosteoblasts and ATDC5 chondrocytes. Histology and biochemical analysis showed enhanced extracellular matrix production and demonstrated collagen and glycosaminoglycan deposition. Expression of genes specific for bone, calcified cartilage and cartilage were improved in the osteochondral scaffold. Overall, these findings suggest that iterative overlaying of freeze-dried scaffolds and hydrogel matrices prepared by using ECM components in biomimetic ratios to fabricate gradient, multi-layered structures can be a promising strategy without the need for growth factors.

Mechanical characterization and ex vivo evaluation of anticancer and antiviral drug printed bioadhesive film for the treatment of cervical cancer.

As research progresses on personalized medicines, it is clear that personalized and flexible formulations can provide effective treatment with reduced side effects especially for diseases like cancer, characteristic of high patient variability. 2D and 3D printers are frequently reported in the literature for the preparation of pharmaceutical products with adjusted dose and selected drug combinations. However, in-depth characterization studies of these formulations are rather limited. In this paper, ex vivo and mechanical characterization studies of antiviral and anticancer drug printed film formulations designed for personalized application were performed. Effects of the printing process with pharmaceutical formulations such as paclitaxel (PCX):cyclodextrin (CD) complex or cidofovir (CDV) encapsulated into poly(ethylene glycol)-polycaprolactone (PEG-PCL) nanoparticles on the films were evaluated through a series of mechanical characterization studies. Inkjet printing process was found to cause no significant change in the thicknesses of the film formulations, while mechanical strength and surface free energy increased and nano-sized voids in the film structure decreased. According to the mechanical characterization data, the unprinted film had maximum force (Fmax) value of 15.6 MPa whereas Fmax increased to 43.8 MPa for PCX:CD complex printed film and to 37.7 MPa for the antiviral CDV-PEG-PCL nanoparticle printed film. In the light of ex vivo findings of sheep cervix-uterine tissue, bioadhesive properties of film formulations significantly improved after inkjet printing with different drug formulations. It has also been shown that the anticancer formulation printed on the film was maintained at the cervix tissue surface for >12 h. This study has shown for the first time that inkjet printing process does not adversely affect the mechanical properties of the bioadhesive film formulations. It has also been shown that durable bioadhesive film formulations for personalized dosing can be prepared by combining nanotechnology and inkjet printing.

Effect of selective infiltration etching on the bond strength between zirconia and resin luting agents.

OBJECTIVE: To evaluate the shear bond strength of resin cements to zirconia treated with the selective infiltration etching technique (SIE). MATERIALS AND METHODS: Forty-seven zirconia specimens were prepared with a sequence of silicon carbide abrasives, cleaned in an ultrasonic bath. Three samples were separated for atomic force microscope (AFM) analyses (one nontreated for control, one sandblasted, and one selective infiltration etched) and the remaining were randomly distributed in four groups, according to the combination of surface treatment and resin cement: group 1a (sandblasting + Variolink II), group 1b (sandblasting + Panavia SA Plus), group 2a (SIE + Variolink II), group 2b (SIE + Panavia SA Plus). A composite resin cylinder (3 mm × 3 mm) was cemented to the zirconia surface, as per each group's specific protocol. After storing 24 hours in distilled water at 37°C, the specimens were tested for shear bond strength and the results were subjected to statistical analysis. RESULTS: At 24 hours, the highest SBS values were observed in group 2b, where the SIE technique was used in conjunction with Panavia SA Plus. Lowest values were found in group 1a. Increased surface roughness was observed with SIE. CONCLUSIONS: SIE significantly enhanced the resin bond strength to zirconia. However, cement selection was also an important factor, for both surface treatments tested. CLINICAL SIGNIFICANCE: Use of SIE method combined with MDP monomer containing resin cement can provide clinically acceptable bond strength between zirconia and resin cement.

In vitro shear bond strength between fluorinated zirconia ceramic and resin cements.

PURPOSE: The purpose of this study was to evaluate the efficiency of a gas-phase fluorination method under different fluorination periods through using two resin cements. MATERIALS AND METHODS: 84 zirconia specimens in dimensions of 5 mm × 5 mm × 2 mm were prepared and surface treated with 50 µm aluminum oxide particles or gas phase fluorination for 2 min, 5 min, or 10 min. One specimen in each group was surface analyzed under scanning electron microscope. The remaining specimens were bonded to composite cylinders in dimensions of 2 mm diameter and 3 mm high with Panavia SA Plus or Variolink N. Then, the specimens were stored in 37℃ distilled water for 24 hours and shear bond strength test was applied at a speed of 1 mm/min. RESULTS: The highest shear bond strength values were observed in the samples fluorinated for 5 minutes and cemented with Panavia SA Plus. Variolink N did not elicit any statistical differences between surface treatments. Panavia SA Plus resin cement and Variolink N resin cements featured statistically significant difference in shear bond strength values only in the case of 5 minutes of fluorination treatment. CONCLUSION: According to the results of this study, application of 5 minutes of fluorination with 10-methacryloyloxydecyl dihydrogen phosphate monomer (MDP) containing Panavia SA Plus resin cement increased the resin bond strength of zirconia. Fluorination of the zirconia surface using conventional resin cement, Variolink N, did not lead to an increase in bond strength.

Influence of nano alumina coating on the flexural bond strength between zirconia and resin cement.

PURPOSE: The purpose of this in vitro study is to examine the effects of a nano-structured alumina coating on the adhesion between resin cements and zirconia ceramics using a four-point bending test. MATERIALS AND METHODS: 100 pairs of zirconium bar specimens were prepared with dimensions of 25 mm × 2 mm × 5 mm and cementation surfaces of 5 mm × 2 mm. The samples were divided into 5 groups of 20 pairs each. The groups are as follows: Group I (C) - Control with no surface modification, Group II (APA) - airborne-particle-abrasion with 110 µm high-purity aluminum oxide (Al2O3) particles, Group III (ROC) - airborne-particle-abrasion with 110 µm silica modified aluminum oxide (Al2O3 + SiO2) particles, Group IV (TCS) - tribochemical silica coated with Al2O3 particles, and Group V (AlC) - nano alumina coating. The surface modifications were assessed on two samples selected from each group by atomic force microscopy and scanning electron microscopy. The samples were cemented with two different self-adhesive resin cements. The bending bond strength was evaluated by mechanical testing. RESULTS: According to the ANOVA results, surface treatments, different cement types, and their interactions were statistically significant (P<.05). The highest flexural bond strengths were obtained in nanostructured alumina coated zirconia surfaces (50.4 MPa) and the lowest values were obtained in the control group (12.00 MPa), both of which were cemented using a self-adhesive resin cement. CONCLUSION: The surface modifications tested in the current study affected the surface roughness and flexural bond strength of zirconia. The nano alumina coating method significantly increased the flexural bond strength of zirconia ceramics.

The Effect of Ascorbic Acid (Vitamin C) on Transepithelial Corneal Cross-Linking in Rabbits.

PURPOSE: To evaluate the effects of ascorbic acid (vitamin C), the main antioxidant agent in the cornea on transepithelial corneal cross-linking (CXL) where the main mechanism is oxidation. METHODS: Twenty eyes of 20 rabbits were divided into 3 groups: Group 1 (7 eyes) had transepithelial corneal CXL after being fed with normal diet; Group 2 (7 eyes) had corneal CXL after once-daily subcutaneous injections of 200 mg of ascorbic acid in addition to normal diet; and the control group (6 eyes) was fed with normal diet but did not have corneal CXL performed. Ascorbic acid levels were measured in aqueous humor and plasma, and biomechanical measurements were applied to the cornea. RESULTS: There was a significant difference in ascorbic acid levels of plasma (P = 0.008) and aqueous humor (P = 0.006) between group 1 and 2. The Young's modulus values of group 1 and 2 were similar (P = 0.741) and were significantly higher than the control group (P = 0.02 and P = 0.01). The increase rate in Young's modulus values was 37.3% in group 1 and 43.9% in group 2 compared to control group. The ultimate strain values in group 1 and 2 were similar (P = 0.632) and were significantly higher than control group (P = 0.04, P = 0.03). The ultimate stress values in group 1 and 2 were similar (P = 0.836) and were significantly lower than control group (P = 0.001, P = 0.001). CONCLUSIONS: Systemic vitamin C does not appear to decrease effectiveness of transepithelial corneal CXL. Therefore, there is no reason to stop or reduce vitamin C supplementation before corneal CXL therapy.

Effects of Hot Chemical Etching and 10-Metacryloxydecyl Dihydrogen Phosphate (MDP) Monomer on the Bond Strength of Zirconia Ceramics to Resin-Based Cements.

PURPOSE: The purpose of this in vitro study was to evaluate the hot chemical etching method on the shear bond strength between zirconia and two resin cements. MATERIALS AND METHODS: Sixty zirconia specimens (13 × 7.5 × 2.5 mm3 ) were prepared and treated as follows: (1) airborne-particle abrasion with 50 µm Al2 O3 particles; (2) hot chemical etching for 10 minutes; (3) hot chemical etching for 30 minutes. Sixty composite cylinders of 3 mm diameter and height were prepared and bonded to zirconia specimens, which were divided into subgroups A and B. Group A: cemented with conventional resin cement (Variolink II); group B: cemented with 10-metacryloxydecyl dihydrogen phosphate (MDP) monomer containing resin cement (Panavia SA) after the application of surface treatments. Next, the specimens were stored in 37ºC distilled water for 24 hours. Following water storage, shear bond strength test was performed at a 1 mm/min crosshead speed in a universal testing machine. The statistical analyses were performed with one-way ANOVA and post hoc Tukey tests. p < 0.05 was considered statistically significant. RESULTS: The results from all of the tested groups exhibited lower shear bond strength values than group II-B and higher shear bond strength values than group I-A (p < 0.05). CONCLUSION: The use of the hot chemical etching method for 10 minutes increased the shear bond strength of zirconia ceramics to both conventional and resin cements and seems to be an effective method. The MDP monomer-containing resin cement, Panavia SA, improved the resin bonding of zirconia ceramics when combined with airborne-particle abrasion.

Design and optimization of novel paclitaxel-loaded folate-conjugated amphiphilic cyclodextrin nanoparticles.

As nanomedicines are gaining momentum in the therapy of cancer, new biomaterials emerge as alternative platforms for the delivery of anticancer drugs with bioavailability problems. In this study, two novel amphiphilic cyclodextrins (FCD-1 and FCD-2) conjugated with folate group to enable active targeting to folate positive breast tumors were introduced. The objective of this study was to develop and characterize new folated-CD nanoparticles via 3(2) factorial design for optimal final parameters. Full physicochemical characterization studies were performed. Blank and paclitaxel loaded FCD-1 and FCD-2 nanoparticles remained within the range of 70-275nm and 125-185nm, respectively. Zeta potential values were neutral and -20mV for FCD-1 and FCD-2 nanoparticles, respectively. Drug release studies showed initial burst release followed by a longer sustained release. Blank nanoparticles had no cytotoxicity against L929 cells. T-47D and ZR-75-1 human breast cancer cells with different levels of folate receptor expression were used to assess anti-cancer efficacy. Through targeting the folate receptor, these nanoparticles were efficiently engulfed by the breast cancer cells. Additionally, breast cancer cells became more sensitive to cytotoxic and/or cytostatic effects of PCX delivered by FCD-1 and FCD-2. In conclusion, these novel folate-conjugated cyclodextrin nanoparticles can therefore be considered as promising alternative systems for safe and effective delivery of paclitaxel with a folate-dependent mechanism.

The effect of environmental humidity on radiation-induced degradation of carrageenans.

Better understanding of the chemistry of radiation-induced degradation is becoming of increasing importance on account of the utilization of polymeric materials in a variety of radiation environments as well as beneficial uses of degraded polymers. In this report the importance of environmental humidity on the degrading effect of radiation has been considered from the point of view of controlling the molecular weights of kappa- and iota-carrageenans. These two polysaccharides were irradiated in solid form under strictly controlled environmental humidity conditions by incubating and later irradiating the samples over saturated aqueous salt solutions of NaCl, NaNO3 and MgCl2. The degradation was followed in detail by a careful gel permeation chromatographic analysis of their respective molecular weights before and after irradiation. The chain scission yield values G(S) were found to decrease with the water adsorbed from environment at every absorbed dose in the range of 5-100 kGy. On the other hand at very high water uptakes the yield of chain scission again increases especially at low doses. The decrease in degradation yield was attributed to the plastifying effect of water trapped in between the polymer chains facilitating the macroradical recombinations thus reducing the extent of chain scission. This study showed that although carrageenans were irradiated in solid form, the difference in their water uptake from changing environmental humidity has a profound effect in controlling their molecular weights by irradiation with ionizing radiation.

Swelling and mechanical properties of superabsorbent hydrogels based on Tara gum/acrylic acid synthesized by gamma radiation.

The main objective is to develop a new superabsorbent system especially for using in diaper applications. In this study, hydrogels based on Tara gum/acrylic acid (TG/AAc) were prepared by gamma irradiation, in the presence of N,N'-methylenebisacrylamide (MBAAm) as a crosslinking agent. The polymeric networks formed were characterized by FT-IR and evaluated by swelling studies as a function of MBAAm concentration, temperature and nature of the swelling medium. The swelling kinetics of the hydrogels was studied in terms of the diffusion exponent "n". The results showed that the water diffusion into hydrogels is a non-Fickian type. Mechanical measurements (stress-strain) curves of hydrogels were evaluated to calculate the shear modulus values and the average molecular weight between crosslinks (Mc). Moreover, the absorption under load at 37°C of water and urea aqueous solutions (as a major component of urine) by TG/AAc hydrogels was determined.

[The investigation of fasciolosis in cattle by copro-ELISA and stool examination techniques around the Derinkuyu region]. / Derinkuyu Yöresindeki Sigirlarda Fasciolosisin Kopro-ELISA ve Diski Muayene Yöntemleriyle Arastirilmasi

OBJECTIVE: This study was carried out between September 2008 and June 2009 to determine the prevalence of fasciolosis in cattle in Derinkuyu district of Nevsehir. METHODS: Fecal samples from 198 cattle were technically collected and examined by sedimentation-zinc sulphate flotation technique. Modified McMaster sedimentation technique was applied to the egg positive samples to determine the EPG values. F. hepatica coproantigens in samples were investigated by ELISA. RESULTS: The coprological and antigen ELISA prevalence of fasciolosis were determined as 2.02% and 3.03%, respectively. The mean EPG value in infected cattle was found as 75±22.9. The prevalence of other parasites, Trichostrongylus spp., Eimeria spp., Nematodirus spp., Moniezia spp., Toxocara vitulorum and Ostertagia spp. were determined as 28.3%, 12.6%, 1.5%, 1.0%, 1.0% and 0.5%, respectively. The prevalence of fasciolosis was observed to be higher in the > 3 age group (3.2%) than ≤3 age group (2.9%), however, this difference was not statistically significant (p > 0.05). The prevalence in female and male cattle was found as 3.4% and 4.8% This difference also was not found statistically significant (p > 0.05). The highest prevalence was observed in Fresian with the ratio of 3.5% and this was followed by 2.8% in Rubia Gallega and 2.4% in Brown Swiss. The differences among breeds were not statistically significant (p > 0.05). CONCLUSION: The presence and prevalence of fasciolosis was revealed with this study.

Effects of molecular weight and ratio of guluronic acid to mannuronic acid on the antioxidant properties of sodium alginate fractions prepared by radiation-induced degradation.

In this study, the effects of the molecular weight and ratio of guluronic acid (G) to mannuronic acid (M), G/M, of some sodium alginate (NaAlg) fractions on their antioxidative properties were investigated. Low-molecular-weight-fractions with various G/M were prepared by gamma radiation-induced degradation of NaAlg. Change in their molecular weight was monitored. Antioxidant properties of the fractions with various molecular weight and G/M were evaluated by determining the scavenging ability of 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH()). 50% inhibition concentrations of the 50 kGy-irradiated NaAlgs having molecular weights of 20.5, 17.7, and 16.0 kDa were found to be 11.0, 18.0, and 24.0mg/ml, respectively, whereas the fractions of the same molecular weight with a lower G/M exhibited a better DPPH() scavenging activity. The results demonstrated that its molecular weight and G/M were important factors in controlling the antioxidant properties of NaAlg.

Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors.

Cationic nanoparticles of chitosan (CS), poly-epsilon-caprolactone coated with chitosan (CS-PCL) and poly-epsilon-caprolactone coated with poly-L-lysine (PLL-PCL) were developed to encapsulate intravesical chemotherapeutic agent Mitomycin C (MMC) for longer residence time, higher local drug concentration and prevention of drug loss during bladder discharge. Nanoparticle diameters varied between 180 and 340 nm depending on polymer used for preparation and coating. Zeta potential values demonstrated positive charge expected from cationic nanoparticles. MMC encapsulation efficiency depended on hydrophilicity of polymers since MMC is water-soluble. Encapsulation was increased by 2-fold for CS-PCL and 3-fold for PLL-PCL as a consequence of hydrophilic coating. Complete drug release was obtained with only CS-PCL nanoparticles. On the other hand, CS and PLL-PCL nanoparticles did not completely liberate MMC due to strong polymer-drug interactions which were elucidated with DSC studies. As far as cellular interaction was concerned, CS-PCL was the most efficient formulation for uptake of fluorescent markers Nile Red and Rhodamine123 incorporated into nanoparticles. Especially, CS-PCL nanoparticles loaded with Rhodamine123 sharing hydrophilic properties with MMC were selectively incorporated by bladder cancer cell line, but not by normal bladder epithelial cells. CS-PCL nanoparticles seem to be promising for MMC delivery with respect to anticancer efficacy tested against MB49 bladder carcinoma cell line.

Intravenous theophylline decreases post-dural puncture headaches.

Post-dural puncture headache (PDPH) is a common complication of lumbar puncture. As invasive treatments for PDPH have known complications, pharmacologic management may be preferable. The aim of this study was to evaluate and to compare the efficacy of intravenous theophylline treatment for PDPH, in comparison with a placebo. We found that intravenous theophylline infusion was effective for decreasing the painfulness of PDPH compared with the control group. The mean visual analogue scale (VAS) value was 7.05+/-1.47 before the theophylline infusion and 2.88+/-2.31 after infusion. An average of 59.1% relief of pain was obtained in the group treated with theophylline infusion. The improvement in VAS in the study group was significant (p < 0.001), whereas that in the control group was not (p = 0.15). The mean VAS decrease after theophylline infusion was 4.17+/-2.03 in the study group and 0.41+/-0.71 in the control group; the difference in improvement between the groups was significant (p < 0.001). Intravenous theophylline infusion is an easy, rapid, minimally invasive, an effective treatment for PDPH. It may be attempted in PDPH patients before invasive techniques are used. To the best of our knowledge, this is the first report on the effect of intravenous infusion of theophylline compared with a placebo in the treatment of PDPH.

Development of nonsurfactant cyclodextrin nanoparticles loaded with anticancer drug paclitaxel.

In the current formulation of clinical use paclitaxel (PCX) is associated with solubilizers that may produce severe side effects. In this study, PCX was complexed to an amphiphilic cyclodextrin (CD), 6-O-CAPRO-beta-CD, capable of forming nanoparticles spontaneously in order to mask its physicochemical properties via the formation of inclusion complexes of the drug with amphiphilic CD before the nanoparticle is formed. Complexes have been characterized with various techniques such as (1)H NMR, Fourier Transform Infrared (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) confirming the formation of inclusion complex between PCX and 6-O-CAPRO-beta-CD. Nanospheres and nanocapsules were prepared directly from the preformed PCX/6-O-CAPRO-beta-CD inclusion complex by the nanoprecipitation technique, showing a size from 150 to 250 nm for nanospheres and from 500 to 500 nm for nanocapsules. Zeta potentials of the nanospheres and nanocapsules indicate stable colloidal dispersions within the range of -18 to -39 mV. A 12-month physical stability was demonstrated for blank nanoparticles. PCX encapsulation was high with three-fold increase in loading when nanoparticles are prepared directly from preformed inclusion complexes of the drug with 6-O-CAPRO-beta-CD. In vitro liberation profiles of PCX from CD nanoparticles show a prolonged release profile for this drug up to 12 h for nanospheres and 24 h for nanocapsules.

Effect of drug physicochemical properties on in vitro characteristics of amphiphilic cyclodextrin nanospheres and nanocapsules.

Nanospheres and nanocapsules of an amphiphilic beta-cyclodextrin, beta-CDC6, were evaluated using a group of steroid drugs to determine the effect of drug physicochemical properties (e.g. partition coefficient, drug:CD association constant k1:1, aqueous solubility) on loading and release profiles of the nanoparticles. Model drugs used were hydrocortisone, testosterone and progesterone. Inclusion complexes were formed between model drugs and beta-CDC6 by the co-lyophilization technique and were characterized by DSC analysis and FTIR spectroscopy. Nanospheres and nanocapsules were prepared directly from these inclusion complexes and alternatively by the conventional preparation technique. It was observed that loading depended highly on the technique used. For nanospheres, drug characteristics played a significant role while for nanocapsules this factor had no significant effect on loading values. Release of drugs from nanospheres was completed in 2h, regardless of drug physicochemical properties with high-loading technique. On the other hand, drug release from nanocapsules was largely dependent on drug properties. Only 30% of progesterone was released in 24h, while hydrocortisone was completely released in 8h. Thus, drug properties are significant for the formulation of nanocapsules and nanospheres. Desired loading and release properties could be achieved by selecting the appropriate drug delivery system and the optimum drug.