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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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Related in: MedlinePlus

Venom activity neutralization by ASVS after acid digestion and intestinal absorption in simulated gut conditions.(A) Schematic diagram of ex vivo simulation of acid digestion in stomach; (B) In vitro Naja naja venom and Daboia russelii venom phospholipase A2 inhibitory activity of normal ASVS, released ASVS which was not acid digested and acid digested released ASVS. Result showed as mean ±SEM, n = 6. *# p<0.05 was considered significant (* Venom control vs normal ASVS, released ASVS, and digested ASVS, # Alginate vs normal ASVS, released ASVS, and digested ASVS). (C) Schematic diagram of ex vivo simulation of intestinal absorption; (D) Pharmacokinetics of FITC tagged ASVS absorption from outer intestinal fluid by monitoring FITC intensity in spectroflurometer; (E) Monitoring of ASVS concentration in outer intestinal fluid for 4 h; (F) Monitoring of ASVS from FITC intensity within the intestinal layer of mice after 4 h.
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pntd-0003039-g003: Venom activity neutralization by ASVS after acid digestion and intestinal absorption in simulated gut conditions.(A) Schematic diagram of ex vivo simulation of acid digestion in stomach; (B) In vitro Naja naja venom and Daboia russelii venom phospholipase A2 inhibitory activity of normal ASVS, released ASVS which was not acid digested and acid digested released ASVS. Result showed as mean ±SEM, n = 6. *# p<0.05 was considered significant (* Venom control vs normal ASVS, released ASVS, and digested ASVS, # Alginate vs normal ASVS, released ASVS, and digested ASVS). (C) Schematic diagram of ex vivo simulation of intestinal absorption; (D) Pharmacokinetics of FITC tagged ASVS absorption from outer intestinal fluid by monitoring FITC intensity in spectroflurometer; (E) Monitoring of ASVS concentration in outer intestinal fluid for 4 h; (F) Monitoring of ASVS from FITC intensity within the intestinal layer of mice after 4 h.

Mentions: Acid digestion of particle was made by placing alginate: ASVS:: 1∶1 beads in 0.1M HCl for 1 h and then the encapsulated ASVS was recovered by placing the beads in phosphate buffer (pH 7.0) for assessing its activity. In the activity study it was found that the released ASVS from alginate: ASVS:: 1∶1 acid digested beads showed significant protection by 41.09% against PLA2 enzyme activity of Naja naja venom and by 43.16% against PLA2 enzyme activity of Daboia russelii venom which was not significantly different in released ASVS from alginate: ASVS:: 1∶1 beads which was not acid digested. This data indicates that alginate entrapment might protect ASVS to overcome the damage caused by the acidic environment of the gastrointestinal tract (Fig. 3A, 3B).


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)

Venom activity neutralization by ASVS after acid digestion and intestinal absorption in simulated gut conditions.(A) Schematic diagram of ex vivo simulation of acid digestion in stomach; (B) In vitro Naja naja venom and Daboia russelii venom phospholipase A2 inhibitory activity of normal ASVS, released ASVS which was not acid digested and acid digested released ASVS. Result showed as mean ±SEM, n = 6. *# p<0.05 was considered significant (* Venom control vs normal ASVS, released ASVS, and digested ASVS, # Alginate vs normal ASVS, released ASVS, and digested ASVS). (C) Schematic diagram of ex vivo simulation of intestinal absorption; (D) Pharmacokinetics of FITC tagged ASVS absorption from outer intestinal fluid by monitoring FITC intensity in spectroflurometer; (E) Monitoring of ASVS concentration in outer intestinal fluid for 4 h; (F) Monitoring of ASVS from FITC intensity within the intestinal layer of mice after 4 h.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0003039-g003: Venom activity neutralization by ASVS after acid digestion and intestinal absorption in simulated gut conditions.(A) Schematic diagram of ex vivo simulation of acid digestion in stomach; (B) In vitro Naja naja venom and Daboia russelii venom phospholipase A2 inhibitory activity of normal ASVS, released ASVS which was not acid digested and acid digested released ASVS. Result showed as mean ±SEM, n = 6. *# p<0.05 was considered significant (* Venom control vs normal ASVS, released ASVS, and digested ASVS, # Alginate vs normal ASVS, released ASVS, and digested ASVS). (C) Schematic diagram of ex vivo simulation of intestinal absorption; (D) Pharmacokinetics of FITC tagged ASVS absorption from outer intestinal fluid by monitoring FITC intensity in spectroflurometer; (E) Monitoring of ASVS concentration in outer intestinal fluid for 4 h; (F) Monitoring of ASVS from FITC intensity within the intestinal layer of mice after 4 h.
Mentions: Acid digestion of particle was made by placing alginate: ASVS:: 1∶1 beads in 0.1M HCl for 1 h and then the encapsulated ASVS was recovered by placing the beads in phosphate buffer (pH 7.0) for assessing its activity. In the activity study it was found that the released ASVS from alginate: ASVS:: 1∶1 acid digested beads showed significant protection by 41.09% against PLA2 enzyme activity of Naja naja venom and by 43.16% against PLA2 enzyme activity of Daboia russelii venom which was not significantly different in released ASVS from alginate: ASVS:: 1∶1 beads which was not acid digested. This data indicates that alginate entrapment might protect ASVS to overcome the damage caused by the acidic environment of the gastrointestinal tract (Fig. 3A, 3B).

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