1. Attiva and Gellica, Two Novel
Superabsorbent Biodegradable Hydrogels,
Decrease Food Intake in Rats
Hassan M. Heshmati1, MD; Eyal S. Ron1, PhD; Yishai Zohar1; Nissim Bilman1; Christian Demitri1, PhD;
Gitte Hansen2, MD; Jana Procházková3; Martin Šlais3, PhD; Mircea D. Bucevschi4, PhD; Monica Colt4, PhD;
Mendy Axlerad4; Alessandro Sannino5, PhD; Luigi Ambrosio6, PhD; Luigi Nicolais7, PhD.
1 Gelesis, Inc., Boston, MA, USA; 2 Gubra, Frederiksberg, Denmark; 3 BioTest sro., Konárovice, Czech Republic;
4 Exotech Bio Solutions, Ltd., Kiryat Gat, Israel; 5 University of Salento, Lecce, Italy;
6 National Research Council of Italy, Naples, Italy; 7 University of Naples, Naples, Italy.
i n t r o d u c t i o n
O v e r w e i g h t a n d o b e s i t y are becom-ing
major health problems worldwide (1). The
World Health Organization (WHO) estimated that
in 2005, approximately 1.6 billion adults around
the globe were overweight and 400 million were
obese. WHO projects that by 2015, these numbers
will reach 2.3 billion and 700 million, respectively.
The therapeutic benefit of all currently available
anti-obesity tools is limited by their marginal effi-cacy
and variable tolerability and safety profiles.
A need exists for a product that is able to re-duce
stomach volume in a manner compara-ble
to bariatric surgery or an intragastric bal-loon,
but with a risk-benefit profile acceptable
to the entire population of overweight/obese
subjects. An intervention that reduces stomach
volume, increases elastic response and viscos-ity
of the upper gastrointestinal content, and
extends gastric emptying time could potential-ly
be very beneficial.
Attiva and Gellica are two novel superabsor-bent
biodegradable hydrogels that are able to
swell in the stomach and the small intestine in
the presence of water and gastrointestinal flu-ids.
Both can swell approximately 100 times their
weight in the gastric and the intestinal environ-ments.
Attiva degrades in the colon while Gell-ica
degrades in the small intestine. The swelling
rate of the two hydrogels in the different parts
of the gastrointestinal tract has been demon-strated
in vitro (Figure 1).
By occupying the gastric and the intestinal cavi-ties,
increasing the gastric emptying time, and
delaying the absorption of glucose in the small
intestine, Attiva and Gellica can induce satiety
and cause food intake reduction.
A previously unpublished study in rats showed that
the administration of 40 mg of Gellica hydrated
with 4 mL of water before the administration of
2 mL of liquefied food causes longer gastric emp-tying
time (Figure 2). Additional observations of
the content of rats’ stomachs after gavage with
hydrated Gellica showed that the hydrogel was
mixed homogenously with the subsequently con-sumed
food (Figure 3c). In fasting rats, the hydrat-ed
hydrogel was found in the stomachs for 30 to
60 min (Figures 3a and 3b) while in rats that were
fed after the administration of Gellica, the hydro-gel
was present in the stomachs for 90 to 120 min.
A study in humans has shown that single admin-istration
of 2 g of Attiva significantly increases
the post-meal feeling of satiety and decreases
the feeling of hunger before the subsequent
meal (Figures 4 and 5) (2). This effect on the
subsequent meal (second meal effect) sug-gests
that the hydrogel could have additional
effect on food intake even after leaving the
stomach (intestinal effect).

2. o b j e c t i v e
The aim of this study was to assess and compare the effect of acute administration
of Attiva and Gellica on food intake in rats.
Thirty-two male Sprague-Dawley rats aged 8 weeks were studied.
F i g u r e 1
a n i m a l s
Stomach Content (g) F i g u r e 3 a F i g u r e 3 b F i g u r e 3 c
Time in Simulated Gastric/Intestinal/Colon Fluids (min)
F i g u r e 2
Time After Administration (min)
Excised rat’s stomach 30 min after
the gavage with 50 mg Gellica
hydrated with 5 mL of water.
Stomach content of a fasting rat
30 min after administration of 50 mg
Gellica hydrated with 5 mL of water.
Stomach content of a fed rat 70 min
after administration of 50 mg Gellica
hydrated with 5 mL of water. Based
on the calculation of consumed
food, approximately 80% of the food
bolus was hydrated hydrogel.
In Vitro Modeling of Swelling Capacity of Attiva
and Gellica in the Gastrointestinal Tract.
(Estimated ratio of swelling g/g)
Effect of Gellica on Rats’ Stomach Content.
(40 mg Gellica hydrated
with 4 mL of water)
Swelling Ratio (g/g)
Stomach Small Intestine Colon
 4 mL hydrogel
+ 2 mL food
 4 mL water
+ 2 mL food
(control)
Attiva
Gellica

3. F i g u r e 4 F i g u r e 5
Placebo-Adjusted Change in Satiety Scores (%)
in Humans After Administration of 2 g of Attiva
Figure 4. Placebo-adjusted change in satiety scores (%) in
humans after administration of 2 g of Attiva at breakfast,
at Breakfast, Lunch, and Dinner.
Placebo-Adjusted Change in Hunger Score (%)
Figure 5. in Placebo-Humans adjusted Before Lunch change and in Dinner, hunger score After
(%) in
humans before lunch and dinner, after administration of 2
Administration of 2 g of Attiva at Breakfast and Lunch.
20
15
10
5
0
30 min
60 min
lunch, and dinner.
* **
**
**
Percent
*P **P < 0.01
5
0
-5
-10
-15
-20
g of Attiva at breakfast and lunch.
Dinner
Pre-meal
*
Percent
Percent
*P < 0.02
F i g u r e 6 F i g u r e 7
Time (min) Time (h)
m e t h o d s
Twenty to 100 mg of Attiva and Gellica were
hydrated in a ratio of 1:100 (polymer to tap wa-ter).
Rats were gavaged with the resulting mix-ture
or an equal volume of water. Animals were
randomized into 3 weight-matched groups,
each receiving either hydrated Attiva, hydrat-ed
Gellica, or water alone (control or vehicle).
The rats were housed individually in MANI Feed-win
cages. The room environment was con-trolled
(temperature: 22 ± 2°C; humidity: 50 ±
10%; light/dark cycle: 12 h light, from 3 am to
3 pm, 12 h dark). Animals had ad libitum ac-cess
to Altromin 1321 powdered diet (20 h/day,
from 3 pm to 11 am) and tap water (24 h/day).
Food intake was recorded every 5 min for 18 h
following the administration of Attiva/Gellica/
vehicle. A 7-day habituation to the system was
allowed before the first administration of the
test agents.
Statistical evaluation was performed with anal-ysis
of variance (ANOVA).
Cumulative Food Intake (% of Vehicle) in Rats
Within 4 h After Administration of 80 mg of
Hydrogels Hydrated With 8 mL of Water.
Cumulative Food Intake (% of Vehicle) in Rats
Within 18 h After Administration of 80 mg of
Hydrogels Hydrated With 8 mL of Water.
Breakfast Lunch Dinner
 30 min
 60 min
**P < 0.05
**P < 0.01 Lunch Dinner
 Pre-meal
**P < 0.02
Cumulative Food Intake
(% of vehicle)
Cumulative Food Intake
(% of vehicle)
ANOVA factorial, Fisher’s post-hoc test
a. P < 0.05 (Gellica vs. vehicle)
b. P < 0.05 (Attiva vs. vehicle)
ANOVA factorial, Fisher’s post-hoc test
a. P < 0.05 (Gellica vs. vehicle)
b. P < 0.05 (Attiva vs. vehicle)
Vehicle (water)
Gellica
Attiva
Vehicle (water)
Gellica
Attiva

4. r e s u l t s
Administration of 80 and 100 mg of Attiva and
Gellica hydrated with 8 and 10 mL of water, re-spectively,
significantly decreased food intake
for up to 18 h (Figures 6 and 7) compared to ad-ministration
of the same amounts of water alone.
Administration of 60 mg hydrated with 6 mL of
water had a significant effect for a shorter period
of time (up to 4 h) while administration of lower
amounts (20 and 40 mg) showed a trend for re-duction
of food intake without statistical signifi-cance.
In most cases, the pattern of food intake
reduction was similar with the two hydrogels.
d i s c u s s i o n
The results of this study demonstrate a significant
decrease in food intake in rats with Attiva and
Gellica and are in agreement with the hydrogel
properties observed in the in vitro gastrointes-tinal
simulations (Figure 1) and observations of
the effects on gastric emptying in rats (Figures
2, 3a, 3b, and 3c).
Some heterogeneities in the results (dose-response
patterns) are probably due to the fact that the
rats were in their active growing period and the
amounts of hydrogels were not adjusted to their
new weight during the study.
While previous observations showed that hydrat-ed
Gellica lasts in the rat’s stomach for up to ap-proximately
c o n c l u s i o n
r e f e r e n c e s
60 min in fasting animals and 120 min
in fed animals, the observed reduction in food in-take
for up to 18 h in the present study supports
the hypothesis of an effect on the small intestine.
Acute oral administration of Attiva and Gellica,
novel superabsorbent biodegradable hydro-gels,
significantly decreases food intake in rats
when compared to administration of a similar
amount of water.
This effect on food intake is probably due to a
combination of transient reduction of the avail-able
stomach volume and delayed gastric
emptying. Additional mechanisms involving the
small intestine could also be present.
This animal data is consistent with the previously
reported human data with Attiva (2).
The observed effects in rats, if confirmed by
chronic administration in humans, will provide
a promising new approach in the treatment of
overweight and obesity.
1. Bessesen DH. Update on obesity. J Clin Endocrinol Metab, 2008, 93, 2027-2034.
2. Heshmati HM, Tacchino R, Ron E, Sannino A, Zohar Y. Attiva, a novel superabsorbent biodegradable
hydrogel, increases the feeling of satiety in humans. In: Program of the 19th Annual Meeting and
Clinical Congress of the American Association of Clinical Endocrinologists, April 21–25, 2010;
Boston, MA, USA. Abstract #605.
The content of this document was presented in a Poster at Obesity 2010,
28th Annual Scientific Meeting, San Diego, California, October 8–12, 2010.