Biodegradable three-dimension micro-device delivering 5-fluorouracil in tumor bearing mice

Ren, Xianyan; Zheng, Na; Gao, Yang; Chen, Tianning; Liu, Wen

doi:10.3109/10717544.2011.635720

Cited by 10 publications

(10 citation statements)

References 40 publications

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“…In this way, local drug delivery enhanced the drug therapeutic efficacy and decreased systemic side effects. Recent local drug delivery systems were mainly used for treating tumor and chronic infectious diseases [1,2]. In order to manufacture drug delivery devices that could release drug smoothly, and for the drug release rate to reach or close to zero order, researchers studied various drug loading devices, including doughnut shaped tablets, multilayer tablets and microparticles etc.…”

Section: Introductionmentioning

confidence: 99%

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

Zheng

et al. 2014

BioMed Eng OnLine

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BackgroundLocal slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro.MethodsThree different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope.ResultsThe PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility.ConclusionsThree dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic.

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Section: Introductionmentioning

confidence: 99%

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

Zheng

et al. 2014

BioMed Eng OnLine

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“…This was contrasted with our model where the drug delivery was maintained over a longer period of time, resulting in sustained tumor kill. Ren et al also treated sarcoma tumors by delivering 5-FU using a biodegradable micro-device made out of poly-(lactic-co-glycolic) acid with some success [31]. While these studies and our current report employ different delivery systems, all have shown that intra-tumoral delivery of chemotherapy can successfully decrease tumor growth, demonstrating that this is a viable treatment strategy.…”

Section: Discussionmentioning

confidence: 75%

Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth

Harris

Coburn

Kajdacsy-Balla

et al. 2016

Journal of Pediatric Surgery

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Background Sarcoma accounts for 20% of solid tumors in children. Surgery has significant morbidity. We hypothesized that delivering chemotherapy directly into tumors through sustained release silk systems could slow tumor growth. Methods Human Ewing sarcoma cells A673 were cultured with vincristine and doxorubicin to determine half maximal inhibitory concentration (IC50). Cells were injected into mouse hind leg to create orthotopic tumors. Tumor volumes were measured using ultrasound. When volume reached >250mm3, interventions included: implantation of drug-free silk foam (Control-F), doxorubicin 400μg foam (Dox400-F), vincristine 50μg foam (Vin50-F), drug-free silk gel (Control-G), vincristine 50μg gel (Vin50-G), or single dose intravenous vincristine 50μg (Vin50-IV). End-point was volume >1,000mm3. Kaplan Meier and ANOVA were used. Results IC50 for vincristine and doxorubicin were 0.5ng/mL and 200ng/mL, respectively. There was no difference between Dox400-F [6±1 days to end point (DTEP)] and Control-F (5±1.3 DTEP). Vin50-F (12.4±3.5 DTEP) had slower growth compared to Control-F (p<0.001), and no difference between Vin50-F and Vin50-IV (14±0 DTEP). Growth was slowest with Vin50-G, 28±10.3 DTEP compared to all other treatment groups (p<0.05). Conclusion Sustained delivery of vincristine inside the sarcoma tumor with silk gel decreased tumor growth. Applying this intra-tumoral treatment strategy may potentially decrease the extent of surgical excision.

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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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Biodegradable three-dimension micro-device delivering 5-fluorouracil in tumor bearing mice

Cited by 10 publications

References 40 publications

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth

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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