Chimica  |  Biochimica  |  Medicina

 

Roberto Londino, 2005 | Mezzovico-Vira, TI
Henry Slater, 2005 | Lugano, TI

 

Our work was about finding a development of a new method to regulate the absorbance of salicylic acid, because it presents problems due to its acid characteristics.
After an initial study on the theoretical principles that regulate the absorbance and the distribution of the drug between the lipidic and aqueous phase of tissues, we experimentally investigated how the breakdown equilibrium is affected by pH.
Next, we sought to regulate absorption by using the properties of alginates: the objective was to produce alginate beads that can go through the gastrointestinal system without releasing salicylic acid in the stomach (pH < 3) but releasing it in the intestine (pH7). Experimentally, we observed that pH-controlled release of salicylic acid from alginate beads occurs at pH 7. However, in this form, the passage across the cell membrane by simple diffusion is very small.

Argomento

The project of our work was to find an alternate use to a common drug: acetylsalicylic acid, by using the pharmacological properties of alginates. Amid the many topics we researched, we focalized ourselves on the absorption at various pHs.

Metodologia

We initially studied the absorbance of salicylic acid through a simple diffusion membrane model at pH 1.2, 2 and 5.3 by building a three-phase model. The model has a salicylic acid solution at the various pHs, a 1-octanol phase that connected the two tanks and simulated the phospholipid membrane, and distilled water. We thus went to measure the conductivity in the tank containing the distilled water, representing adsorption.
Then we created calcium alginate beads (cross-linking time of 15 minutes) containing a salicylate solution; this way we could increase the solubility of salicylic acid and thus its concentration. Then we placed them in a solution of HCl at pH 1, and in a buffer at pH 7. We then added six drops of iron chloride and measured the absorption at a 565 nm wavelength of the iron salicylate complex coloration of the solution containing the beads.

Risultati

The results are divided in two sections, first is pH-related diffusion of salicylic acid across a membrane model, in this experiment we had different conductivity values across three different pHs, at a pH of 1 we had 25 microS/(cm.h)of conductivity, at pH 2 we had similar but higher values, while at pH 5.3 the conductivity further decreased to 7 microS/ (cm.h).
Next is the pH-dependant release of salicylic acid from alginate beads, the beads at pH 7 quickly released all of their contents, the salicylate bonded to the iron ions and the solution turned purple, we recorded an absorbance of green light at 565 nm at a maximum of 0.248. The release can be further demonstrated due to the increase in pH in time. Before the alginate beads are inserted in water the pH of the distilled water is 7, after they release the salicylate the pH increases to 9, The salicylate increases the pH since it’s a base. In contrast, at pH 1 we had no or a negligible release, with an absorbance of green light (565 nm) of 0.035.

Discussione

As we intended our results for the three-phase experiment reflected our theoretical calculations, the greatest absorption through the membrane occurs in its acid form, at a pH under 3.
Regarding the second experiment we demonstrated that in our system there is a release at a pH of 7, while at a pH of 1 the release is almost nil. However at a pH of 7 the absorption through the membrane is low (as shown through the three-phase experiment).

Conclusioni

From the gathered results we can conclude that our alginate beads are able to keep salicylic acid in a solution at a pH of 1 while releasing it at a pH of 7. However, from our theoretical calculations, we noted that the transfer through the membrane of salicylic acid is not favored at pHs greater than its pKa of 3, because it is in in the ionic form and goes through the membrane with more difficulty; nonetheless, since the intestine has a very large surface area for absorption, the drug might still be absorbed.
If one wanted to further increase absorption, one could integrate TPGS (D-alfa-Tocopheryl polyethylene glycol succinate) into the alginate beads, a molecule that increases the lipophilicity of substances, simplifying their passage through the membrane.
One aspect that could be further explored is how release varies with cross-linking time, but keeping in mind that there is release already during cross-linking.

 

 

Valutazione del lavoro espressa dall’esperto

Dr. Albert Ruggi

Questo lavoro si propone di trovare una soluzione al problema degli effetti negativi dell’acido salicilico a carico dello stomaco usando sfere di alginato per un rilascio controllato e dipendente dal pH dell’ambiente. Gli studenti dimostrano un grande interesse per la chimica farmaceutica, una buona capacità di documentazione, progettazione, esecuzione degli esperimenti ed analisi dei risultati.

Menzione:

buono

 

 

 

Liceo cantonale di Lugano 2, Lugano-Savosa
Docente: Giancarlo Parisi