TITANYUM DIOKSIT KATI LIPIT NANOPARTIKLLERI

1
OCULAR DESIGN OF CYCLOSPORINE-A SOLID LIPID
NANOPARTICLES
Ebru BASARAN, Müzeyyen DEMIREL, Yasemin YAZAN
Anadolu University, Faculty of Pharmacy,
Department of Pharmaceutical Technology 26470
Eskisehir- TURKEY
INTRODUCTION
RESULTS
Cyclosporine A (CsA) is a powerful
immunosuppressive active agent mainly used for
autoimmune diseases and graft rejections after
organ transplantations 1. Topical application
of CsA is preferred for the ocular treatment of
disorders after corneal transplantation and dry
eye syndrome 2. Solid lipid nanoparticles
(SLN) were introduced as alternative carrier
systems for controlled release of pharmaceutical
and cosmetic active compounds 3. Particles of
the system remain in the solid state at room
temperature and therefore the mobility of
incorporated drug is reduced which is a
prerequisite for controlled drug release 4.
Possibility of controlled drug release and drug
targeting, increased drug stability, high drug
payload, incorporation of both lipophilic and
hydrophilic drugs, avoidance of organic solvents
and no problem with respect to large scale
production and sterilization were the proposed
advantages of SLNs 5. Systemic absorption of
CsA is quite low and there is interindividual
variation in plasma concentrations depending on
the dosage form applied and the story of the
patient 6. Therefore, in this study, cationic
SLNs were prepared, aiming the ocular delivery of
CsA with an attempt to decrease the
interindividual variation and thus to increase
its topical absorption. MATERIALS Cyclosporine
-A Novartis, Switzerland Active agent
(Gift) Dynasan 116 Condea, Germany Solid
lipid Stearylamine Fluka, USA Cationic agent
Benzalconium chloride Fluka, Denmark
Antimicrobial agent Tween 80 Merck,
Germany Surfactant METHODS SLN formulation
(Table 1) was prepared by hot homogenization
technique 4. Homogenization was achieved with
Ultraturrax (T25, IKA) at a stirring rate of
13500 rpm for 5 minutes, at 85ºC1ºC. Table 1.
Composition of the formulation As the
sterility of the ocular formulations is
necessary, the formulation was sterilized by
autoclaving at 121C for 20 minutes. Particle
size and zeta potential measurements were carried
out by Malvern Nano ZS and the structure of the
solid lipid was analyzed using differential
scanning calorimetry (DSC-60, Shimadzu), X-Ray
Diffractometry (XRD) (RIKAGU D/Max-3C), Fourier
Transform Infrared Spectrophotometry (FT-IR)
(Perkin Elmer Spektrum 2000) and solid state NMR
Spectrophotometry (1H-NMR). Stability of the
formulation was monitored for 6 months at
different conditions (25ºC1ºC, 40ºC1ºC,
4ºC1ºC). In vivo studies were carried on the
sheep. Formulation was applied topically to one
of the eyes and the other eye remained untreated
as a reference. At appropriate time intervals,
sheep were sacrificed and the aqueous and
vitreous humour samples were collected and
analyzed by enzyme immune assay analyzer.
Particle sizes (Figure 1) and the zeta potentials
(Figure 2) of the formulation remained unchanged
during the storage at different conditions
(25ºC1ºC, 40ºC1ºC, 4ºC1ºC) for a period of 6
months. Stability of the lipid structure
analyzed by XRD (Figure 3), FT-IR (Figure 4) and
1H-NMR (Figure 5) showed that these data support
the DSC data (Figure 6) indicating the stability
of the formulations for 6 months.
EXPERIMENTAL
CONCLUSION
According to the in vitro tests results, cationic
SLN formulation remained stable during the
storage period of 6 months. After the topical
application of the formulation to the eyes,
detection of CsA at the deeper layers, and no
existence of interindividual variance in the CsA
concentrations showed the efficiency of SLN
formulation on the absorption of such a
problematic drug.
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This study was financed by Anadolu University
Scientific Research Project Foundation
6th World Meeting on Pharmaceutics,
Biopharmaceutics and Pharmaceutical Technology,
7-10 April 2008-Barcelona-Spain