Matrices for site-specific controlled-delivery of 5-fluorouracil to descending colon

Zambito, Ylenia; Baggiani, Angelo; Carelli, V.; Serafini, M.F.; Colo, Giacomo Di

doi:10.1016/j.jconrel.2004.11.001

Cited by 36 publications

(18 citation statements)

References 17 publications

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“…ChHCl was prepared as previously described. 13 Fluorescein isothiocyanate (FITC) was from Sigma-Aldrich. The QA-Ch conjugates QA-Ch50 and QA-Ch60 and thiolated derivatives QA-Ch50-SH and QA-Ch60-SH were synthesized from Ch according to Zambito et al 10 For the Ch derivatives, the figures 50 and 60 refer to the respective temperatures (°C) at which the synthesis was carried out.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

Fabiano¹,

Bizzarri²,

Zambito³

2017

IJN

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A thermosensitive ophthalmic hydrogel (TSOH) – fluid at 4°C (instillation temperature), semisolid at 35°C (eye temperature), which coupled the dosing accuracy and administration ease of eyedrops with the increased ocular bioavailability of a hydrogel – was prepared by gelling a chitosan hydrochloride (ChHCl) solution (27.8 mg/mL) medicated with 1.25 mg/mL 5-fluorouracil (5-FU) with β-glycerophosphate 0.8 mg/mL. Polymer mixtures, where Ch was partially (10%, 15%, or 20%) replaced by quaternary ammonium–chitosan conjugates (QA-Ch) or thiolated derivatives thereof, were also used to modulate 5-FU-release properties of TSOH. Also, Ch-based nanoparticles (NPs; size after lyophilization and redispersion 341.5±15.2 nm, polydispersity 0.315±0.45, ζ-potential 10.21 mV) medicated with 1.25 mg/mL 5-FU prepared by ionotropic cross-linking of Ch with hyaluronan were introduced into TSOH. The 5-FU binding by TSOH polymers in the sol state was maximum with plain Ch (31.4%) and tended to decrease with increasing QA presence in polymer mixture. 5-FU release from TSOH with or without NPs was diffusion-controlled and linear in √t. The different TSOH polymers were compared on a diffusivity basis by comparing the slopes of √t plots. These showed a general decrease with NP-containing TSOH, which was the most marked with the TSOH, where Ch was 20% replaced by the derivative QA-Ch50. This formulation and that not containing NP were instilled in rabbits and the 5-FU transcorneal penetration was measured by analyzing the aqueous humor. Both TSOH solutions increased the area under the curve (0–8 hours) 3.5 times compared with the plain eyedrops, but maximum concentration for the NP-free TSOH was about 0.65 μg/mL, followed by a slow decline, while the NP-containing one showed a plateau (0.25–0.3 μg/mL) in a time interval of 0.5–7 hours. This is ascribed to the ability of this TSOH to control drug release to a zero order and that of NPs to be internalized by corneal cells

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Section: Materials and Methods Materialsmentioning

confidence: 99%

Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

Fabiano¹,

Bizzarri²,

Zambito³

2017

IJN

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“…However, on arrival in the descending colon where pH is greater than 7, the Eudragit film coat dissolves and the drug is released in a controlled fashion from the matrices. In vitro release studies conducted in simulated GIT environment provided good evidence for the proof of concept that successful targeting to the descending colon could be achieved 53 . In order to avoid the burst release pattern of ondansetron from chitosan microspheres Jose et al, encapsulated the optimized chitosan microspheres with Eudragit S-100 by solvent evaporation technique.…”

Section: 2mentioning

confidence: 92%

Multiparticulate Combined Approaches for Colon Specific Drug Delivery

Pradhan¹

2011

Int Jour of Biomed Res

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In order to achieve a successful colon targeted drug delivery system, a drug needs to be protected from degradation, release and/or absorption in the upper portion of the gastrointestinal tract (GIT) and then ensure abrupt or controlled release in the proximal colon. Such a system can be formulated by utilizing microbial triggering degradation of polymer coating/ gastro intestinal (GI) transit time (time dependent)/ pH dependent approach etc. But unfortunately it has been found that colonic microflora, GI transit time and pH varies considerably inside a human system by several factors, in addition to this the native biodegradable polysaccharides which are used widely for the microbial triggering colonic drug delivery system (CDDS), are having high aqueous solubility on account of which a single unit colon targeted drug delivery systems may suffer from dose dumping due to overall catastrophic failure of the film around a monolith, which would then release the whole drug, that may lead to drastically compromised systemic drug bioavailability or loss of local therapeutic action in the colon. This review emphasizes some of the causes which make a single unit dosage form unsuitable for targeting to colon by using microbial triggering/GI transit time/pH dependent approach, and at the same time discusses researches which have been carried out to alleviate these problems by utilizing multiparticulate combined approaches.

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“…As a systemic injection of 5-FU often leads to systemic toxic side-effects, tumor in situ sustained-release microspheres or a hydrogel delivery system will certainly improve the antitumor effects of the drug (13,14). Different delivery systems for 5-FU have been developed, including microsphere delivery systems (15), nanospheres (16), 5-FU microspheres for brain tumor therapy (17), 5-FU microspheres for malignant glioma therapy (18), 5-FU hydrogels for drug administration in vivo (19), matrix microspheres containing a 5-FU coat using Eudragit S100 (20), and nanoscale-particles for topical delivery (21), to name just a few (22)(23)(24)(25)(26)(27)(28)(29). The specific delivery system can reduce the systemic toxicity and prevent anticancer drug degradation (30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

Development of a 5-fluorouracil-loaded PLGA microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method for the treatment of tumors

et al. 2014

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Abstract. Tumor treatment requires a long-term regimen of chemotherapy, and both surgical tumor resection and radiation therapy are also used. The present study aimed to develop a novel method for 5-fluorouracil (5-FU)-loaded microspheres which enhance the therapeutic effects of chemotherapy, the quality of life of patients and reduce chemotherapy systemic side-effects. The preparation of a 5-FU microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method was carried out and then in vitro and in vivo evaluation of the 5-FU-microsphere delivery system was conducted. The 5-FU microsphere delivery system prepared had sustainedrelease function and achieved local treatment efficacy for tumors. The encapsulation efficiency of the 5-FU microsphere delivery system was >90% [better than the fabrication method using water-in-oil-in-water (W/O/W)]. The drug release profile from the 5-FU-loaded sustained-release microsphere delivery system matched the pseudo zero-order equation for 30 days in vitro. The plasma concentration of 5-FU was higher than the water solution by subcutaneous injection. The tumor growth rate of rabbits using the 5-FU microsphere delivery system was much lower than the rate in rabbit using a subcutaneous injection of 5-FU water solution. The 5-FU-loaded sustainedrelease microspheres using the novel method (S/O/hO) is a potential and effective method with which to inhibit tumor growth.Introduction 5-Fluorouracil (5-FU) is one of the classical drugs for tumor chemotherapy (1,2). It has been used for colorectal tumors (3-6), pancreatic cancer (5,6), actinic keratosis (7,8) and breast tumors (9-12). As a systemic injection of 5-FU often leads to systemic toxic side-effects, tumor in situ sustained-release microspheres or a hydrogel delivery system will certainly improve the antitumor effects of the drug (13,14). Different delivery systems for 5-FU have been developed, including microsphere delivery systems (15), nanospheres (16), 5-FU microspheres for brain tumor therapy (17), 5-FU microspheres for malignant glioma therapy (18), 5-FU hydrogels for drug administration in vivo (19), matrix microspheres containing a 5-FU coat using Eudragit S100 (20), and nanoscale-particles for topical delivery (21), to name just a few (22-29). The specific delivery system can reduce the systemic toxicity and prevent anticancer drug degradation (30-33). However, different methods have different weaknesses such as low encapsulation efficiency, burst release or insufficient duration for drug release.We previously developed various preparation methods for biological molecular protein drug delivery such as the waterin-oil-in-hydrophilic oil-in-water (W/O/hO/W) method (34), solid-in-oil-in-oil-in-water (S/O/O/W) method (35-37), and solid-in-oil-in-hydrophilic oil-in-ethanol (S/O/hO/E) method (38,39,40). The chemical agents were not microencapsulated in the microspheres using these preparation methods. The present study aimed to develop a 5-FU-loaded sustained-release microsphere system using a novel meth...

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Matrices for site-specific controlled-delivery of 5-fluorouracil to descending colon

Cited by 36 publications

References 17 publications

Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

Multiparticulate Combined Approaches for Colon Specific Drug Delivery

Development of a 5-fluorouracil-loaded PLGA microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method for the treatment of tumors

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