Amount Of 5-fluorouracil Research Articles

Polymer-Coated Polymeric (PCP) Microneedles for Controlled Dermal Delivery of 5-Fluorouracil.

Polymeric microneedles were prepared with Polyvinyl Pyrrolidone (PVP) K-30 using the mold casting technique. The core microneedles were coated with Eudragit E-100 by dip and spin method. The amount of 5-fluorouracil (FU) loaded in the core microneedles was 604 ± 35.4µg. The coating thickness was 24.12 ± 1.12µm. The objective was to deliver the 5-FU gradually in a controlled release manner at the target site in the sub-stratum corneum layer. This approach is anticipated to improve the safety and efficacy of topical melanoma treatment. The release of the drug was prolonged for up to 3h from the polymer-coated polymeric (PCP) microneedles. The entire amount was found to release within 15min in uncoated MNs. Likewise, the permeation of the drug from the uncoated microneedles was rapid, whereas the PCP microneedles were able to prolong the permeation up to 420min. The PCP microneedles were subjected to stability studies at 25°C ± 2°C/60%RH, and 40°C ± 2°C/75%RH condition for 3months. The formulations were found intact, and the release rate was not significantly different form the fresh formulation. The drug content was found to meet the acceptability criteria as well (98.12 ± 1.8% and 97.8 ± 2.1% at 25 and 40°C respectively after 3months). Overall, this study demonstrated the feasibility of fabrication of PCP microneedles using Eudragit E100 for intraregional controlled delivery of drugs.

An acellular tissue matrix-based drug carriers with dual chemo-agents for colon cancer growth suppression

Background/aimsRelapse, metastasis, and chemo-resistance are the main factors responsible for the failure of surgical treatment of malignant tumors, and typically are the main obstacles to effective cancer treatment. Although significant advances have been made in the field of cancer chemotherapy, many patients still receive inadequate treatment due to the severe adverse effects of these drugs, resulting in an inability to reach therapeutic concentrations at the tumor site with systemic chemotherapy. Thus, a biological patch loaded with chemotherapeutic drugs could be an ideal strategy for the treatment of cancer at the tumor site. MethodsWe developed an acellular matrix using the submucosa of porcine jejunum, then loaded this matrix with different amounts of 5-fluorouracil (5-FU) and rapamycin nanoparticles. Cell proliferation and apoptosis were analyzed by flow cytometry and related markers were evaluated using real-time PCR and western blotting. The patches were evaluated in vitro to characterize their release kinetics and therapeutic feasibility. We then analyzed the therapeutic efficacy and systemic toxicity of these patches in vivo by using them in a mouse model of colon cancer. ResultsThe patches delivered 5-FU and rapamycin in a controlled manner for more than 8 weeks, arrested the cell cycle of LoVo cells and sw480 cells at G2/M phase, and induced apoptosis in vitro. The patches also suppressed the growth of xenografted tumors in vivo with lower adverse effects than typically observed with systemic administration of these drugs. ConclusionWe demonstrated that patches loaded with 5-FU-RAPA-PLA-NP significantly inhibited the growth of colon cancer in vitro and in vivo. These results demonstrated the feasibility of the use of a multi-effect biological patch for cancer treatment.

Synthesis and Characterization of 5-Fluorouracil-Loaded Glutaraldehyde Crosslinked Chitosan Hydrogels

In this work, the characterization and drug release behavior of 5-fluorouracil-loaded glutaraldehyde-crosslinked chitosan hydrogels have been studied. The structure of the hydrogels were investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, also their properties were compared with those of the drug-unloaded hydrogels. The equilibrium swelling studies and drug release profiles were determined at 37°C in two different pHs (2.1 and 7.4). The results indicated that increased chitosan concentration in the hydrogel decreased the swelling and drug release values and the hydrogels released nearly the same amount of 5-fluorouracil in both acidic (~59%) and basic medium (~50%).

In vitro study of ethosome penetration in human skin and hypertrophic scar tissue

The purpose of this study is to characterize a novel transdermal delivery carrier, ethosomes containing 5-fluorouracil. The delivery of drugs from ethosomes in human hypertrophic scar (HS) and the mechanisms of action of ethosomes in human HS were investigated. Percutaneous ethosome permeation was evaluated in vitro in human HS and skin using a Franz's cell. The amount of 5-fluorouracil that permeated HS and skin after 24 hours was most abundant in ethosomes via HS (E-Scar), followed by hydroethanolic solution via HS (H-Scar), ethosomes via skin (E-Skin), and hydroethanolic solution via skin (H-Skin). The penetration of ethosomes in HS and skin was analyzed by ethosomes fluorescently labeled with rhodamine 6GO using confocal laser scanning microscopy. The fluorescence intensity after application for 24 hours was highest in E-Scar, followed by E-Skin, H-Scar, and H-Skin, which indicates the penetration of ethosomes in HS was greatest. In conclusion, we consider that ethosomes are a highly efficient carrier in HS. From the Clinical EditorIn these ex vivo experiments, the authors studied ethosome penetration in human skin and hypertrophic scar tissue. It was concluded that ethosomes are superior in 5-fluorouracyl delivery compared to standard hydroethanolic solution, paving the way to future clinical studies.

Development of 5-fluorouracil loaded poly(acrylamide- co-methylmethacrylate) novel core-shell microspheres: In vitro release studies

Novel poly(acrylamide-methylmethacrylate) copolymeric core-shell microspheres crosslinked with N, N′-methylene bisacrylamide have been prepared by free radical emulsion polymerization using varying amounts of acrylamide (AAm), methylmethacrylate (MMA) and N, N′-methylene bisacrylamide (NNMBA). 5-Fluorouracil was loaded into these microspheres during in situ polymerization (method-I) as well as by the absorption and adsorption technique (method-II). The core-shell microspheres have been characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (X-RD) to understand about the drug dispersion in microspheres. Scanning electron microscopy (SEM) was used to assess the surface morphology of particles prepared. In vitro release of 5-fluorouracil has been studied in terms of core-shell composition, amount of crosslinking agent and amount of 5-fluorouracil in the microspheres. Core-shell microspheres with different copolymer compositions have been prepared in yields ranging 80–85%. DSC and X-RD techniques indicated a uniform distribution of 5-fluorouracil particles in core-shell microspheres, whereas SEM suggested the formation of well-defined core-shell structures. The in vitro drug release indicated that particle size and release kinetics depend upon copolymer composition, amount of crosslinking agent used and amount of 5-fluorouracil present in the microspheres. Prolonged and controlled release of 5-fluorouracil was achieved when drug was loaded by method-I instead of method-II.

Thymidine phosphorylase activity in tumor correlates with venous invasion.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenesis factor. We investigated the correlation between dThdPase activity in gastric cancer tissue and clinicopathological factors. Thirty-three cancer tissue specimens and 23 adjacent normal gastric mucosal specimens were obtained from surgery. Measurement of dThdPase activity was based on the amount of 5-fluorouracil formed from 5'-deoxy-5-fluorouridine by dThdPase. Mean dThdPase activity in cancer tissue was approximately 3.2 times higher than that in normal tissue. Cancerous tissues with venous invasion had about twice the dThdPase activity as cancerous tissues without venous invasion. Other clinicopathological features were not related to dThdPase activity. A correlation between dThdPase activity and immunosuppressive acidic protein level was observed (r = 0.532, P = 0.005). dThdPase activity in gastric cancer cells was found to be correlated with venous invasion, supporting previous findings that it plays a role in tumor angiogenesis.

The significance of measuring RNA 5-fluorouracil content in gastrointestinal tract tumors after oral administration of UFT

Background Prior to surgery, UFT [combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil in a 1∶4 molar ratio] was orally administered to 32 patients with cancer of the gastrointestinal tract. During the operation the amount of 5-fluorouracil (5FU) concentration in the RNA (F-RNA) was mesured in normal and tumor tissues. Simultaneously, the 5FU concentration and thymidylate synthase (TS) inhibition rates were determined.

The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice.

The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.

Preparation of a polymer containing hexadecylpyridinium bromide groups and its utilization as a transdermal drug penetration enhancer

A novel polymeric transdermal penetration system was investigated. The polymer was synthesized by the reaction of poly(4-vinylpyridine) and hexadecyl bromide, and its enhancing activity on drug penetration was evaluated by means of in vitro experiments. The amount of 5-fluorouracil (5-FU) that permeated through the skin was determined by using a two-chamber diffusion cell, in which isolated rabbit abdominal skin was mounted. Addition of the polymer effectively enhanced the penetration rate of 5-FU. The permeability coefficient was 2–8 times as much as that in the absence of the polymer. The enhancing activity increased with increase in the degree of quaternization. The mechanism was investigated by differential scanning calorimetry of whole skin and stratum corneum treated with the polymer. Through this investigation, it was shown that, although the polymer interacted with the lipids and proteins of the membranes of the stratum corneum, it may not penetrate into deeper layers of the skin. The absence of irritation of the polymer to the skin was confirmed by the Draize test.

Tolerance of Extended (28 Day) Continuous Infusion of 5-Fluorouracil in Advanced Head and Neck Cancer

Since continuous exposure increases the cytotoxicity of 5-Fluorouracil, this agent is now commonly administered by 4-5 day continuous infusions. However Phase I studies have suggested that infusion of doses up to 450 mg/m2/day for at least 28 days may be possible. In the present study 12 patients with advanced head and neck cancer were treated with continuous infusion 5-Fluorouracil at starting doses of 400-450 mg/m2/day for 28 days followed by a 14 day rest period. Patients received a median of 2.5 cycles over 10 weeks for a median total 5-Fluorouracil dose of 12,700 mg/m2. One patient achieved Partial Response. Significant stomatitis (Grade II or greater) was seen more frequently than predicted from Phase I studies (8/12 patients) and was the most common cause for dose reduction. Diarrhea, emesis, palmar/plantar syndrome and skin rash were also noted. No significant myelosuppression was seen. Extremely large amounts of 5-Fluorouracil can be delivered to head and neck cancer patients by extended infusion. However due to the high frequency of stomatitis in this population, lower starting doses than those used in this study may be required.

Trabeculectomy With 5-Fluorouracil for Adult Inflammatory Glaucoma

We reviewed the records of 12 eyes of ten adult patients with inflammatory glaucoma who underwent trabeculectomy with the adjuvant use of 5-fluorouracil between January 1986 and January 1989. Intraocular pressure decreased from 36 +/- 10 mm Hg (range, 17 to 50 mm Hg) preoperatively to 11 +/- 4 mm Hg (range, 3 to 17 mm Hg) postoperatively after a median follow-up of 7.75 months (range, six to 38 months). All eyes achieved an intraocular pressure of less than 20 mm Hg, and ten of 12 required no intraocular pressure lowering medications. The mean (+/- S.D.) amount of 5-fluorouracil used was 33 +/- 10 mg (range, 20 to 55 mg). During the period of observation, five of 12 eyes had an episode of uveitis, but in no patient did this result in loss of intraocular pressure control. Preoperative and postoperative systemic and topical corticosteroid use was the same. Trabeculectomy with 5-fluorouracil is an effective treatment for selected cases of adult inflammatory glaucoma refractory to medical management.

Compatibility of 5-fluorouracil and total parenteral nutrition solutions.

The physicochemical stability and availability of 0.1% 5-fluorouracil solutions in D5W and a typical total parenteral nutrition solution (hypertonic dextrose and crystalline amino acids) were studied in both glass and Viaflex delivery systems. Serial samples collected over a 48-hour period were assayed for 5-fluorouracil concentration using a high performance liquid chromatographic technique. Changes in the pH as well as precipitate formation were also investigated. There was no reduction in the amount of 5-fluorouracil at 48 hours in either the glass or plastic system, regardless of whether the drug was added to D5W or to the total parenteral nutrition solution. No pH changes or precipitates were observed. These findings indicate that 5-fluorouracil is compatible with and available from total parenteral solutions of hypertonic dextrose and amino acid in both plastic and glass containers. Use of such a system would allow for (1) a reduction in vascular access in patients receiving both treatments and (2) continued administration of nutritional support without the requirement for additional fluid volume.