Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach.
Vaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0219912 |
| _version_ | 1818584294585532416 |
|---|---|
| author | Ee Wern Tan Kean Yuen Tan Li Voon Phang Palanirajan Vijayaraj Kumar Lionel L A In |
| author_facet | Ee Wern Tan Kean Yuen Tan Li Voon Phang Palanirajan Vijayaraj Kumar Lionel L A In |
| author_sort | Ee Wern Tan |
| collection | DOAJ |
| description | Vaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the years, probiotic-based peptide delivery vehicles comprising of lactic acid bacteria such as Lactococcus lactis has emerged as an interesting alternative due to its generally recognized as safe (GRAS) status, a fully sequenced genome, transient gut colonization time, and is an efficient cellular factory for heterologous protein production. However, its survivability through the GI tract is low, thus better delivery approaches are being explored to improve its bioavailability. In this study, we employ the incorporation of a double coated mucoadhesive film consisting of sodium alginate and Lycoat RS 720 film as the inner coat. The formulated film exhibits good mechanical properties of tensile strength and percent elongation for manipulation and handling with an entrapment yield of 93.14±2.74%. The formulated mucoadhesive film is subsequently loaded into gelatin capsules with an outer enteric Eudragit L100-55 coating capable of a pH-dependent breakdown above pH 5.5 to protect against gastric digestion. The final product and unprotected controls were subjected to in vitro simulated gastrointestinal digestions to assess its survivability. The product demonstrated enhanced protection with an increase of 69.22±0.67% (gastric) and 40.61±8.23% (intestinal) survivability compared to unprotected controls after 6 hours of sequential digestion. This translates to a 3.5 fold increase in overall survivability. Owing to this, the proposed oral delivery system has shown promising potential as a live gastrointestinal vaccine delivery host. Further studies involving in vivo gastrointestinal survivability and mice immunization tests are currently being carried out to assess the efficacy of this novel oral delivery system in comparison to parenteral routes. |
| first_indexed | 2024-12-16T08:18:53Z |
| format | Article |
| id | doaj.art-4cbbeb69d2f543d1b3a25ada7108eee9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:18:53Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4cbbeb69d2f543d1b3a25ada7108eee92022-12-21T22:38:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021991210.1371/journal.pone.0219912Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach.Ee Wern TanKean Yuen TanLi Voon PhangPalanirajan Vijayaraj KumarLionel L A InVaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the years, probiotic-based peptide delivery vehicles comprising of lactic acid bacteria such as Lactococcus lactis has emerged as an interesting alternative due to its generally recognized as safe (GRAS) status, a fully sequenced genome, transient gut colonization time, and is an efficient cellular factory for heterologous protein production. However, its survivability through the GI tract is low, thus better delivery approaches are being explored to improve its bioavailability. In this study, we employ the incorporation of a double coated mucoadhesive film consisting of sodium alginate and Lycoat RS 720 film as the inner coat. The formulated film exhibits good mechanical properties of tensile strength and percent elongation for manipulation and handling with an entrapment yield of 93.14±2.74%. The formulated mucoadhesive film is subsequently loaded into gelatin capsules with an outer enteric Eudragit L100-55 coating capable of a pH-dependent breakdown above pH 5.5 to protect against gastric digestion. The final product and unprotected controls were subjected to in vitro simulated gastrointestinal digestions to assess its survivability. The product demonstrated enhanced protection with an increase of 69.22±0.67% (gastric) and 40.61±8.23% (intestinal) survivability compared to unprotected controls after 6 hours of sequential digestion. This translates to a 3.5 fold increase in overall survivability. Owing to this, the proposed oral delivery system has shown promising potential as a live gastrointestinal vaccine delivery host. Further studies involving in vivo gastrointestinal survivability and mice immunization tests are currently being carried out to assess the efficacy of this novel oral delivery system in comparison to parenteral routes.https://doi.org/10.1371/journal.pone.0219912 |
| spellingShingle | Ee Wern Tan Kean Yuen Tan Li Voon Phang Palanirajan Vijayaraj Kumar Lionel L A In Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. PLoS ONE |
| title | Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. |
| title_full | Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. |
| title_fullStr | Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. |
| title_full_unstemmed | Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. |
| title_short | Enhanced gastrointestinal survivability of recombinant Lactococcus lactis using a double coated mucoadhesive film approach. |
| title_sort | enhanced gastrointestinal survivability of recombinant lactococcus lactis using a double coated mucoadhesive film approach |
| url | https://doi.org/10.1371/journal.pone.0219912 |
| work_keys_str_mv | AT eewerntan enhancedgastrointestinalsurvivabilityofrecombinantlactococcuslactisusingadoublecoatedmucoadhesivefilmapproach AT keanyuentan enhancedgastrointestinalsurvivabilityofrecombinantlactococcuslactisusingadoublecoatedmucoadhesivefilmapproach AT livoonphang enhancedgastrointestinalsurvivabilityofrecombinantlactococcuslactisusingadoublecoatedmucoadhesivefilmapproach AT palanirajanvijayarajkumar enhancedgastrointestinalsurvivabilityofrecombinantlactococcuslactisusingadoublecoatedmucoadhesivefilmapproach AT lionellain enhancedgastrointestinalsurvivabilityofrecombinantlactococcuslactisusingadoublecoatedmucoadhesivefilmapproach |