Beruflich Dokumente
Kultur Dokumente
DOI 10.1007/s10856-007-0159-5
Received: 26 December 2005 / Accepted: 14 March 2006 / Published online: 1 February 2007
Springer Science+Business Media, LLC 2007
Introduction
Local drug delivery system for treatment of some
diseases received considerable attention during the
past several decades due to its significant merits. It
could achieve predictable and reproducible release of
agents into a specific environment over an extended
period, and also created a desired environment with
optimal response, minimum side-effects and prolonged
efficacy [1, 2]. An ideal formulation should exhibit ease
of delivery, a good retention at the application site and
a controlled release of agents. Cyril et al. [3] developed
a high crosslinked amylose starch matrix as a sustained
antimicrobial delivery system for local prevention or
treatment of osteomyelitis. Marie et al. [4] used
nonionic cellulose ethers as potential carrier systems
for the delivery of local anesthetic agents to the
periodontal pocket. Eve et al. [5] prepared a new type
of chitosan (CS) thermosensitive hydrogel for the
sustained release of paclitaxel at tumor resection sites
in order to prevent local tumor recurrence. Other
synthetic and natural materials were also made into
various formulations. In all formulations prepared with
biomaterials used in this field, micro-particles [6],
bioadhesive gels [7] and films [8] were widely applied
and deeply investigated.
CS got much application in medical field [911] due
to its favorable properties such as biocompatibility,
biodegradability, easily forming gels and films. Carboxymethyl-chitosan (CMCS) derived the reaction of
chloroactic acid and CS in alkaline condition [12].
Compared to CS, some characteristics of CMCS were
more excellent due to assimilating the carboxyl group.
It could easily dissolve in neutral water solution. The
123
1126
123
1127
Dt Dnc
100%
Dpc Dnc
123
1128
123
100
90
80
70
PVA
P2C1
P1C1
P1C2
CMCS
60
50
40
300
400
500
600
700
800
900
1129
PAV film need about 350 min which was much longer
than that of CMCS film (20 min). In addition, time of
drug released completely from the three blend drug
films was intervenient, P2C1(220 min) > P1C1(160 min) > P1C2 (80 min).
Result of release profiles of OD from P1C1 film in
different pH solutions (PBS and citrate buffer) was
shown in Fig. 9. The release rate of OD from blend
system at pH 7.4 was faster than that at pH 3.5. This
phenomenon would be attributed to the pH-responsive
swelling effect of blend films. Although Zhao et al. [25]
speculated that there were large extents of hydrogen
bond between PVA and CMCS in the interpolymer
complexes, it was still supposed that compact polyion
complex between ammonium ion and carboxylate ion
in CMCS instead of hydrogen bonding was formed at
pH 3.5 and resulted a slow drug release rate comparing
with the drug release rate at pH 7.4.
Antimicrobial activity of the blend systems
Figure 10 showed that extracts of PVA/CMCS blend
film inhibited the growth of both E. coli and S. aureus
strain. The inhabitation increased with the increase of
Blank films
Drug films
P2C1
P1C1
P1C2
CMCS
2.351 0.323
4.626 0.521
2.687 0.621
3.456 0.131
0.917 0.133
3.654 0.211
0.836 0.213
2.461 0.197
2.351 0.166
1.565 0.243
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1130
100
Swelling degree
PVA
P2C1
P1C1
P1C2
CMCS
80
60
40
PVA
P2C1
P1C1
P1C2
CMCS
20
20
40
60
80
100
20
40
Time (mins)
60
80
Time(mins)
Fig. 7 The release curves of OD from the films in PBS (pH 7.4)
12
CMCS
Swelling degree
10
PVA
P2C1
P1C1
P1C2
CMCS
P1C2
P1C1
P2C1
4
PVA
2
0
100
200
300
400
pH
100
80
pH7.4
pH3.5
60
40
20
20
40
60
80
Time(mins)
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1131
100
S.aureus
E.coil
80
60
40
20
.0100
.0500
.1000
.2000
Fig. 11 The
photomicrographs of rat
periodontia dealt with the
extracts of PVA/CMCS blend
drug film (a), 0.1 g/mL
formaldehyde solution (b)
and sterilized 0.9% NaCl
solution (c)
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1132
Fig. 12 The
photomicrographs of tissue
response to PVA/CMCS drug
films (a, b) and entwisted silk
suture (c, d) implants in the
subcutaneous tissue after 1
and 4 weeks, respectively
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1133
Table 2 OD release from the PVA/CMCS blend drug as subcutaneous implantation in rats
The tested animals
1
2
3
4
5
6
Mean value
2 days
5 days
278.24
318.74
326.74
286.73
320.12
288.21
303.13
120.06
167.1
183.07
108.11
167.14
112.73
143.04
50.92
59.95
42.76
60.81
33.03
49.49
Conclusion
It concluded from the above study that some characteristics of PVA/CMCS blend films could be controlled
by varying the content of PVA or CMCS. Low swelling
degree and slow drug release rate enhanced by
increasing the PVA component in the system. But
excellent biological properties (such as antibacterial
activity and biocompatibility) could be achieved by
increasing the content of CMCS.
Results of the in vitro and in vivo studies showed
that CMCS/PVA blend drug film was an excellent
candidate for local drug delivery system. It had neither
hemolysis to rabbit blood nor toxicity to rat periodontium. It could offer some antimicrobial activity against
infection and had potential to delivery therapeutic
compounds. The test of subcutaneous implantation
also indicated that the insertion of PVA/CMCS drug
film in the surgical wounds did not promote any
adverse effect. Over a long period of time, it is
expected that the PVA/CMCS drug film would be
absorbed and the wound would be cicatrized by new
forming tissues eventually.
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