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A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil.

Singh S, Kotla NG, Tomar S, Maddiboyina B, Webster TJ, Sharma D, Sunnapu O - Int J Nanomedicine (2015)

Bottom Line: Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects.In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon.In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.

ABSTRACT
Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics), and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Histological features of colons after 30 days treatment.Notes: (A) Nanoparticles of XG:GG, (B) 5-FU powder, (C) 5-FU nanoparticles, (D) probiotics, (E) probiotics + 5-FU powder, and (F) probiotics + 5-FU nanoparticles.Abbreviations: XG, xanthan gum; GG, guar gum; 5-FU, 5-fluorouracil; H&E, hematoxylin and eosin.
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f4-ijn-10-7175: Histological features of colons after 30 days treatment.Notes: (A) Nanoparticles of XG:GG, (B) 5-FU powder, (C) 5-FU nanoparticles, (D) probiotics, (E) probiotics + 5-FU powder, and (F) probiotics + 5-FU nanoparticles.Abbreviations: XG, xanthan gum; GG, guar gum; 5-FU, 5-fluorouracil; H&E, hematoxylin and eosin.

Mentions: Light micrographs of the middle colon suggested that pathological changes were seen among the different groups due to the different treatments given. A microscopy study suggested that the muscular and serosal layers appeared within normal limits. Results showed intact colonic mucosa with an intact epithelial lining of nanoparticles of GG and XG for the treated rats (Figure 4A). Diffuse ulceration of the colonic mucosa with a loss of a lining epithelium was observed for the case of 5-FU powder-treated rats (Figure 4B). But focal ulceration of the colonic mucosa with an intact lining epithelium was observed for the 5-FU nanoparticle-treated rats (Figure 4C). The mucosal layer was infiltrated by mononuclear inflammatory cells predominantly comprising lymphocytes and histiocytes for the case of the probiotic-treated rats (Figure 4D).


A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil.

Singh S, Kotla NG, Tomar S, Maddiboyina B, Webster TJ, Sharma D, Sunnapu O - Int J Nanomedicine (2015)

Histological features of colons after 30 days treatment.Notes: (A) Nanoparticles of XG:GG, (B) 5-FU powder, (C) 5-FU nanoparticles, (D) probiotics, (E) probiotics + 5-FU powder, and (F) probiotics + 5-FU nanoparticles.Abbreviations: XG, xanthan gum; GG, guar gum; 5-FU, 5-fluorouracil; H&E, hematoxylin and eosin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664497&req=5

f4-ijn-10-7175: Histological features of colons after 30 days treatment.Notes: (A) Nanoparticles of XG:GG, (B) 5-FU powder, (C) 5-FU nanoparticles, (D) probiotics, (E) probiotics + 5-FU powder, and (F) probiotics + 5-FU nanoparticles.Abbreviations: XG, xanthan gum; GG, guar gum; 5-FU, 5-fluorouracil; H&E, hematoxylin and eosin.
Mentions: Light micrographs of the middle colon suggested that pathological changes were seen among the different groups due to the different treatments given. A microscopy study suggested that the muscular and serosal layers appeared within normal limits. Results showed intact colonic mucosa with an intact epithelial lining of nanoparticles of GG and XG for the treated rats (Figure 4A). Diffuse ulceration of the colonic mucosa with a loss of a lining epithelium was observed for the case of 5-FU powder-treated rats (Figure 4B). But focal ulceration of the colonic mucosa with an intact lining epithelium was observed for the 5-FU nanoparticle-treated rats (Figure 4C). The mucosal layer was infiltrated by mononuclear inflammatory cells predominantly comprising lymphocytes and histiocytes for the case of the probiotic-treated rats (Figure 4D).

Bottom Line: Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects.In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon.In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.

ABSTRACT
Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics), and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.

No MeSH data available.


Related in: MedlinePlus