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Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

Bhattacharya S, Chakraborty M, Mukhopadhyay P, Kundu PP, Mishra R - PLoS Negl Trop Dis (2014)

Bottom Line: Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required.Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Calcutta, Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India.

ABSTRACT

Background: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.

Methodology/principal findings: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.

Conclusions/significance: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

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Schematic diagram of oral delivery procedure of alginate coated ASVS beads.
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pntd-0003039-g007: Schematic diagram of oral delivery procedure of alginate coated ASVS beads.

Mentions: The gold standard to test ASVS activity is neutralization of venom lethality in animals done by injecting preincubated venom and antivenom in experimental animals. Since oral formulation cannot be pre-incubated we have shown lethality neutralization of ASVS released from alginate bead after crossing the intestinal barriers. This mimics the real situation as empirically as preincubated models and needs new methodology to study efficacy of ASVS as well as oral ASVS (Fig. 7). But the above studies cannot confirm that how much this oral delivery is beneficial as there are lots of other factors involved in it like peristaltic movement, effects of protein digestion enzymes as well as the uptake kinetics. Thus the feasibility of alginate coated ASVS bead to provide sufficient amount of antivenom required for neutralization of venom was studied in animal model. Alginate coated ASVS was given orally by the method of Matsuno et al 2008 [47] with minute modification (Fig. 7). Viper venom induced lethality, hemotoxicity and renal toxicity was chosen as venom toxicity models as these effects are irreversible and are affected by delay in ASVS administration. Alginate coated ASVS was per orally administered in every 30 minutes interval up to 6 hours for hemotoxic and nephrotoxic models and till 24 h for lethal model. Peroral administration of ASVS significantly prevented venom induced toxicity which is depicted by delay in increase of clotting time, inhibition of morphology alteration of RBC, decrease release of free hemoglobin, and low plasma urea and creatinine level as compared with venom induced group of animals. Above all neutralization of MLD has been found after peroral delivery of alginate coated ASVS. From these studies it has been found that oral delivery of alginate coated ASVS prevented the damage caused due to venom administration. The above study confers that oral delivery of ASVS could be possible and it could help to decrease number of deaths occurring due to snake bite in remote places.


Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

Bhattacharya S, Chakraborty M, Mukhopadhyay P, Kundu PP, Mishra R - PLoS Negl Trop Dis (2014)

Schematic diagram of oral delivery procedure of alginate coated ASVS beads.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125299&req=5

pntd-0003039-g007: Schematic diagram of oral delivery procedure of alginate coated ASVS beads.
Mentions: The gold standard to test ASVS activity is neutralization of venom lethality in animals done by injecting preincubated venom and antivenom in experimental animals. Since oral formulation cannot be pre-incubated we have shown lethality neutralization of ASVS released from alginate bead after crossing the intestinal barriers. This mimics the real situation as empirically as preincubated models and needs new methodology to study efficacy of ASVS as well as oral ASVS (Fig. 7). But the above studies cannot confirm that how much this oral delivery is beneficial as there are lots of other factors involved in it like peristaltic movement, effects of protein digestion enzymes as well as the uptake kinetics. Thus the feasibility of alginate coated ASVS bead to provide sufficient amount of antivenom required for neutralization of venom was studied in animal model. Alginate coated ASVS was given orally by the method of Matsuno et al 2008 [47] with minute modification (Fig. 7). Viper venom induced lethality, hemotoxicity and renal toxicity was chosen as venom toxicity models as these effects are irreversible and are affected by delay in ASVS administration. Alginate coated ASVS was per orally administered in every 30 minutes interval up to 6 hours for hemotoxic and nephrotoxic models and till 24 h for lethal model. Peroral administration of ASVS significantly prevented venom induced toxicity which is depicted by delay in increase of clotting time, inhibition of morphology alteration of RBC, decrease release of free hemoglobin, and low plasma urea and creatinine level as compared with venom induced group of animals. Above all neutralization of MLD has been found after peroral delivery of alginate coated ASVS. From these studies it has been found that oral delivery of alginate coated ASVS prevented the damage caused due to venom administration. The above study confers that oral delivery of ASVS could be possible and it could help to decrease number of deaths occurring due to snake bite in remote places.

Bottom Line: Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required.Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Calcutta, Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India.

ABSTRACT

Background: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.

Methodology/principal findings: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.

Conclusions/significance: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

Show MeSH
Related in: MedlinePlus