In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads
The aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca muc...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2018-12-01
|
| Series: | Biomolecular Concepts |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/bmc-2018-0019 |
| _version_ | 1819016132868177920 |
|---|---|
| author | Asnani Geet P. Kokare Chandrakant R. |
| author_facet | Asnani Geet P. Kokare Chandrakant R. |
| author_sort | Asnani Geet P. |
| collection | DOAJ |
| description | The aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery. |
| first_indexed | 2024-12-21T02:42:47Z |
| format | Article |
| id | doaj.art-217f6fd267af4c0ab0e9b697e42976bb |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-21T02:42:47Z |
| publishDate | 2018-12-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-217f6fd267af4c0ab0e9b697e42976bb2022-12-21T19:18:39ZengDe GruyterBiomolecular Concepts1868-50211868-503X2018-12-019119019910.1515/bmc-2018-0019bmc-2018-0019In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beadsAsnani Geet P.0Kokare Chandrakant R.1Sinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa, Pune – 411 048, (affiliated to: Savitribai Phule Pune University), Maharashtra, IndiaSinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Kondhwa, Pune – 411 048, (affiliated to: Savitribai Phule Pune University), Maharashtra, IndiaThe aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.https://doi.org/10.1515/bmc-2018-0019portulaca oleraceamucilagenatural polysaccharidecolon targeting5-fluorouracilbeadsionotropic gelation |
| spellingShingle | Asnani Geet P. Kokare Chandrakant R. In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads Biomolecular Concepts portulaca oleracea mucilage natural polysaccharide colon targeting 5-fluorouracil beads ionotropic gelation |
| title | In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads |
| title_full | In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads |
| title_fullStr | In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads |
| title_full_unstemmed | In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads |
| title_short | In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads |
| title_sort | in vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked portulaca alginate beads |
| topic | portulaca oleracea mucilage natural polysaccharide colon targeting 5-fluorouracil beads ionotropic gelation |
| url | https://doi.org/10.1515/bmc-2018-0019 |
| work_keys_str_mv | AT asnanigeetp invitroandinvivoevaluationofcoloncancertargetedepichlorohydrincrosslinkedportulacaalginatebeads AT kokarechandrakantr invitroandinvivoevaluationofcoloncancertargetedepichlorohydrincrosslinkedportulacaalginatebeads |