HYSTERESIS OF CONTACT ANGLE. DYNAMIC WETTABILITY STUDIES OF COLLAGEN AND DOXYCYCLINE POROUS MATRICES CROSSLINKED
WITH TANNIC ACID
L. POPAa, M. V. GHICAa*, M. G. ALBUb, A. ORTANc, C.-E. DINU-PÎRVUA
a“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Physical and Colloidal Chemistry Department, 6, Traian Vuia, 020956, Bucharest, Romania
bINCDTP – Division Leather and Footwear Research Institute, Collagen Department, 93 Ion Minulescu Str., 031215, Bucharest, Romania
cUniversity of Agronomic Sciences and Veterinary Medicine,
Faculty of Land Reclamation and Environment Engineering, Bucharest, Romania
Collagen porous matrices are promising delivery systems which offer the possibility to obtain a local optimized drug release. One important prerequisite in understanding the drug dissolution profile is an adequate monitoring of the porous collagen matrices surface properties and surface wettability degree. In this study we have considered direct measurements of the contact angle and hysteresis of contact angle (dynamic contact angle) for some collagen matrices with doxycycline, cross-linked with tannic acid, in order to better describe the wettability properties of these drug release systems. The matrices were obtained by freeze-drying of collagen gels (the release support) which have embedded doxycycline as model drug. These systems were prepared at pH=3.8, and crosslinked with different concentrations of tannic acid (4%, 5%, 10%, respectively 20%). We also took into account in the study an uncrosslinked matrix (without tannic acid) as control sample.
A KSV Instrument CAM 101 equipped with a digital camera and the pendant drop method were used for contact angle and surface properties experiments. The liquid (water) is imbibed into the porous matrices producing the contact angle decrease in time. The Young-Laplace equation was applied and the contact angle hysteresis was evaluated (difference between the maximum and the minimum contact angle values) to characterize the surface wettability and hydrophobicity.
(Received May 15, 2013; Accepted July 9, 2013)
Keywords: Contact angle, Hysteresis, Porous matrices, Collagen
1. Introduction
The contact angle is considered as an useful indicator for a solid surface characterization, providing valuable information on wetting properties, hydrophobicity measure of interfacial properties or adsorbtion phenomenon. Generally, wetting involves the interaction of a liquid with a solid and includes the formation of a contact angle [1] at the solid/liquid/fluid interface, the spreading of liquid over the surface, or penetration of a liquid into a porous medium [2]. For topical systems as collagen porous matrices loaded with different drugs, the contact angle and the hysteresis of the contact angle play important roles in systems biocompatibility, on one hand, and in drug local controlled release, one the other hand [3].
It is well known that collagen represents one of the most favourable matrix for on-site drug delivery, due to its excellent biocompatibility, well established safety profile, high biodegradability and very week antigenicity [4-6]. Collagen sponges (also called porous matrices)
**corresponding author: [email protected]
are use formul Collag and tis comple collage disease synerg design wound comple
it is de solid in
sv, sl, the equ
of con maxim recedin directly macrop adsorb topical
crossli collage gel) w acid (
ed in burns, w lations with gen enormou ssue engineer The aim o ete wettabili en loaded w e and crossl gic antibacte ned for on-si ds) and were ete the chara
2. Theor Contact an efined as the ntersect (Fig
Fig. 1 corrrespo
For a smal , lv, the soli uilibrium con
In the case ntact angles mum value fo
ng. The diffe y related to porous matr btion and dru
l administrat 3. Mater
Manufact inked with en hydrogels were obtained (0, 4, 5, 1
wounds and liposomes a us therapeuti
ring [11,12].
f this paper ty characteri with doxycyc linked with erial and ast ite treatment previously d acterization o
retical bac ngle () is a q e angle form gure 1).
- Contact ang ond to partial w
ll liquid drop id-vapour, so ntact angle is
e of imperfec is usually o for contact a
erence betwe the extent of rices or spon
ug release r tion [16,17].
rials and m
uring proc tannic acid s based on 1.
d at pH=3.8.
0 and 20%
plastic surge are applied c potential i
was to evalu ization of po line hyclate a natural ag tringent acti t of periodon described and of these innov
ckground quantitative med by a liqu
gle between a l wetting ( > 0 p deposited o olid-liquid a s defined by
ct, non-homo obtained, thu angle, a is c een advancin
f surface het nge [1, 19,2 rate from the
methods cess for p d. The proc 2% collagen . The hydrog
% reported
ery [7,8], as as controlle is completed uate the cont orous collage – an antibio gent, tannic
ivities [14,1 ntitis disease
d characteriz vative drug r
measure of t uid at the thr
liquid (l) and 0) and (c) corr
on a solid sur and liquid-va
Young’s we lv
.cos
ogenous solid us the term called advan ng and recedi terogeneity, p 20]. All thes e porous ma
porous coll cess was pr n and 0.2% d gels were cr to the dry
well as in pa d transderm d today with tact angle an en matrices. T
otic used for acid [13]. T 5]. These c e, as well as zed [16-18].
release syste
the solid wet ree-phase bo
a flat solid su responds to co
rface, three i apor respecti ell known rel
sv d surfaces, a apparent c ncing and th ing contact a pore size, po se properties atrices loadelagen matr reviously rep doxycycline h rosslinked w
collagen).
arodontology mal drug deli h protein/gen nd contact an These matric r local treatm Tannic acid i
collagen por s for other sk
The wettabil ms.
tting by a liq undary wher
urface (s): (a) omplete wettin
interfacial ten vely. The fo lation:
sl and for porou ontact angle he minimum angles is call orosity and ins are directl ed with drug
rices with ported [13,2 hyclate (repo ith different
A program
y [9]. Collage ivery system ne delivery s ngle hysteres
ces consist in ment of perio
is also used rous matrice kin injuries lity studies c
quid. Geome re a liquid, g
and (b) ng ( = 0).
nsions are in orce balance
us matrices, e is preferre
value, r is led hysteresis
nterconnectiv ly related to g and design
doxyciclin 21,22]. Brief orted to the c t amounts of m of freeze
en - gel ms [10].
systems sis for a n type I odontal for its es were (burns, come to
etrically gas and
nvolved giving
(eq. 1) a range ed. The s called s and is vity for o water ned for
e and fly, the
ollagen f tannic -drying
(lyophilization), using the Delta 2-24 LSC Christ lyophilizer (Germany) was applied to obtain the porous collagen matrices, codified as shown in Table 1.
Table 1Codification of the porous collagen porous matrices.
Collagen porous matrix Tannic acid
%
Doxycycline
% pH
CDA 0% 0.2% 3.8
CDT4 4% 0.2% 3.8 CDT5 5% 0.2% 3.8
CDT10 10% 0.2% 3.8
CDT20 20% 0.2% 3.8
CT4 4% 0% 3.8 CT5 5% 0% 3.8
CT10 10% 0% 3.8
CT20 20% 0% 3.8
Determination of dynamic surface wettability. The contact angle was determined and analysed at room temperature, with a KSV Cam 101 Scientific Instrument, equipped with a digital video camera for images capturing (Helsinki, Finland) [23,24]. The pendant drop dynamic method was applied, using distilled water. The drop shape was monitored with the digital camera, for a time interval up to 12s, and the contact angle, drop diameter, drop height and volume were recorded. The drop shape was mathematically described by the Young-Laplace equation (eq.1) and the contact angle was determined as the slope of the contour line at the three-phase contact point.
The dynamic drop method provided advancing and receding contact angles as function of time. At least six independent measurents on different sponge surface locations (both sides) were averaged.
4. Results and discussions
Collagen porous matrices were evaluated for their surface wettability (contact angle measurements) and contact angle hysteresis was determined. As summarized in Table 2, the values for all contact angle were less than 90, indicating a good hydrophilicity and wettability degree for the top surface.
Table 2. Results of contact angle experiments for collagen porous matrices
Collagen porous matrix Contact angle (˚) Hysteresis (˚)
CDA 58.721.25 84.721.28
CDT4 62.131.06 31.771.22
CDT5 64.961.19 23.551.16
CDT10 84.371.39 7.231.12
CDT20 73.551.03 10.861.09
CT4 57.071.11 35.591.23
CT5 60.031.24 26.931.13
CT10 72.431.15 12.661.01
CT20 67.281.22 15.261.03
or hys CDT10
a) at 0
collage drop w
a low angle constan of cont collage
In the Figs teresis from 0.
.00s Fig. 2. Im
contac
As we exp en porous ma was infiltrated
a) at 0.00s Fig. 3 – Im
contact
For CDT1 hydrophylic hysteresis w nt in time (F
Increasing tact angle (h en porous ma
s. 2 and 3 im image (a) t
b) at 1 mages for drop
ct angle at diff
pected, the atrix without d into the po
b) at 1.8 mages for drop t angle at diffe
Doxyc 0 collagen m city for the p was also sm Fig. 3).
the crosslin hydrophylicit atrices with a
mages of the d o (d), are ex
.82s
p shape, conto fferent time fra
Doxycycline highest valu t crosslinking
rous medium
82s op shape, conto ferent time fram cycline and cr matrices, the h
porous matri mall, while b king agent c ty decrease) a
and without
drop shape f xemplified fo
c) at 5 our line for co ame, for the c e and without ue of contac g agent (alm m in 10s (Fig
c) at 5.47s tour line for co
me, for the co rosslinked wit highest valu ix surface an both the dro concentration and a contac doxycycline
for the decrea or two types
.47s ontact angle ca collagen porou tannic acid) ct angle hys most 85 in ap
g 2).
d) at 9.72 ontact angle c ollagen porous th tannic acid
e for contact nd a small w op contour a n (tannic acid ct angle hyste e (Figure 4 an
ase in time o s of porous m
d) at 9.72 alculation, hys us matrix CDA
teresis was pproximately
2s
calculation, hy s matrix CDT1
10%).
t angle was o wettability d and drop vo d) from 4% t eresis decrea nd 5).
of the contact matrices: CD
2s ysteresis of
A (with
observed at y 10s). Actua
ysteresis of T10 (with
observed, ind degree. The olume were
to 20%, an in ase occurred,
t angle, DA and
t CDA- ally, the
dicating contact almost ncrease for the
0 3 6 9 12 15 0
20 40 60 80 100 120
Contact angle (0 )
Time (s)
CDA CDT4 CDT5 CDT10 CDT20
Fig. 4 – Variation of contact angle for collagen porous matrices without tannic acid (CDA) and for cross-linked matrices with different concentration of tannic acid (4, 5, 10
and 20%).
The exceptions for this linear correlation were noticed for the collagen porous matrices with tannic acid 10% (CDT10 and CT10). For these matrices higher values for contact angle (84.37 and 72.43, respectively) and lower hysteresis (7.23 and 12.66, respectively) were recorded compared to those obtained at 20% concentration of tannic acid.
0 3 6 9 12 15
0 20 40 60 80 100 120
Contact angle (0 )
Time (s)
CT4 CT5 CT10 CT20
Fig. 5 – Variation of contact angle for collagen porous matrices without doxycycline, cross-linked with different concentration of tannic acid (4, 5, 10 and 20%).
These experimental data correlate very well with our previous studies regarding the viscosity of corresponding hydrogel formulations of collagen with doxycycline and tannic acid [16]; the concentration of 10% of tannic acid induced the highest level of cross-linking, the pore size, pore distribution and surface characteristics being directly related to the concentration of tannic acid as cross-linking agent. As in the scanning electron microscopy previous studies, the most uniform structure for porous matrices was obtained for a level of 10% of tannic acid [16], but the hidrophylicity and wettability degree were at lower levels.
For the porous matrices without doxycycline, no evident decrease in hysteresis of contact angle was noticed (for example, from 35.59 at CT4 to 12.66 at CT10). Although doxycicline had its own effect of cross-linking agent [16,17] upon the surface hydrophilicity and wettability degree, the effect of tannic acid is prevalent.
porous
67). T The sm concen matric degree
investi hydrop porous the cro influen have s agent c correla studies
100904
In Fig. 6 s matrices inv
Fig. 6. C
As it can b The hysteresi mallest valu ntration tann es presented e.
5. Concl Porous co igated from philicity can s matrices.
The contac osslinking a nce the surfa shown the lo could be con Some mod ate the dyna s.
Acknowle M.G. Alb 402/2013.
the variation vestigated in
Contact angle w be seen all th
is of contact ues for hyste nic agent indu d average val
lusions ollagen matr
membrane s accelerate t ct angle exp agent concen aces propert owest hydrop nsidered as a dels could be amic wettabi
edgements bu acknow
ns in contac n this study a
and hysteresi ettability and he porous ma angle shows eresis were r uces the high lues for hyste
rices contain surface hydro the water pe periments and
ntration as w ies. The ma philicity and starting poin e further estab
ility studies
ledges to
ct angle and are synthetica
is for the colla hydrophilicity atrices have p s a large inte recorded for hest crosslink eresis around
ning doxycy ophilicity an ermeation an
d recorded c well as the m atrices contai d wettability nt for the opt
blished and with porou
the Progra
d contact ang ally illustrate
agen porous m y of the surfac proved a sati erval of varia r CDT10 an
king level fo d 22 that c
ycline cross nd wettability nd improve d
contact angle matrix poros ining 10% ta degree. Thi timization of further inves us matrices f
am Nucleu
gle hysteres ed.
matrices as ind ces
isfactory hyd ation between nd CT10, res or collagen. M
orrespond to
linked with y degree poi drug diffusio e hysteresis sity are the annic acid ( s concentrat f these promi stigations cou
formulations
CERTEXP
sis for the c
dicator of
drophilicity ( n 84.72 and spectively; f Many of the o a good wet
tannic acid int of view.
on rate throu have indicat major facto (crosslinking
tion of cross ising drug sy uld be develo s, and drug
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(around d 7.23.
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