Ordered Mesoporous Silicas for Drug Delivery in ......Department of Applied Science and Technology...
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Department of Applied Science and Technology
Ordered Mesoporous Silicas for Drug Delivery in
Dermatological Applications
Barbara Onida, R. Mortera, B. Camarota, D. Caldarola, G. Chieregatti, A. Gignone
OMS particles
I. Slowing, J. Vivero-Escoto, C.-W. Wu, V. S.-Y. Lin, Adv. Drug Delivery Rev., 2008, 60, 1278.
M. Vallet-Regí, Chem. Eur. J., 2006, 12, 5934.
M. Vallet-Regí, et al., Chem. Mater. 2001, 13, 308
Department of Applied Science and Technology
OMSS FOR DRUG DELIVERY
THE AIM OF THE STUDY
Products for topical applications on epidermis or mucosa allowing constant therapeutic concentration of the Active Principle Ingredient (API) during controlled time (from hours to days) on the application site, so reducing the number of applications.
Drug therapeutic concentration
Pulsed administration (applications)
toxicity
therapeutic range
inefficacy
time
[D]
Department of Applied Science and Technology
POSSIBLE TOPICAL APPLICATIONS
¢ dermatitis, eczema, psoriasis (corticosteroids, NSAIDs)
¢ Mucosites: 30-40% of chemio-radio therapy patients (antimicrobials, antifungals, antivirals).
¢ WOUNDS, SORES, BURNS (ANTIBIOTICS, ANESTHETICS)
• low vascularization (poor effectiveness of systemic antibiotics) • infection, also related to the medication, is an important issue
• higher efficacy
• better patient compliance
Department of Applied Science and Technology
WHY AMORPHOUS SILICA?
• Amorphous silica particles are widely used in cosmetics.
• Colloidal silica in spray is a source of silicon for the epidermis.
• Silicon is reported to have beneficial effects on the skin: plastic, trophic, antioxidant. Seaborn CD, Nielsen FH, “Silicon deprivation decrease collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver.” Biol. Trace Elem. Res. 2002; 89 (3): 251-61.
Department of Applied Science and Technology
0,00
0,50
1,00
1,50
2,00
2,50
0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4
Salycilic Acid release from MCM-41 in water The release may be described as a drug DISSOLUTION by the Noyes-Whitney equation
Time (hours)
SA
conc
. (m
g/m
l)
( )tsdt CCVAk
dtdC
−⋅=
Noyes-Whitney Equation
( )tsdt CCVAk
dtdC
−⋅=Noyes-Whitney Equation (M. Gibaldi et al. J. Pharm. Sci. 1967, 56, 1238
N.V. Mulye et al. Drug. Dev. Ind. Pharm. 1995, 10, 2599)
• Ct is the salycilic acid concentration at time t
• Cs is the salycilic acid solubility (2.0 mg/ml @ 20°C)
• V is the liquid diffusion volume (10 ml in the present test)
• kd is the dissolution rate constant (0.067 cm/h)
Renkin and Curry, Membrane transport in Biology , Springer-Verlag 1979
kd = D / h
D: diffusion coefficient; h: diffusion layer thickness (lpores)
D = Dwater
A is the accessible surface to diffusion: surface separating the internal mesopore volume and the external solution volume
400 nm
Assuming all particles having the same diamater (400 nm) and the radial disposition of mesopores A can be calculated as Vmes/lpores
0,0 0,2 0,4 0,6 0,8 1,00
100
200
300
400
10 100 1000 10000
Pore size distribution
2,4 nm
p/p0
Vol
ume
STP
(cm
3 /g)
R. Mortera et al., Chemical Engineering Journal 156 (2010) 184–192
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1,00
1,50
2,00
2,50
0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4
SA release NW standard equation
Salycilic Acid release from MCM-41 in water
( )tsdt CCVAk
dtdC
−⋅=
Noyes-Whitney Equation
SA(MCM-41) SA(aq)
Time (hours)
SA
conc
. (m
g/m
l)
0 1 2 3 4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0C
(mg/
ml)
time (hours)
saturated solution 5 mg SA-OMS spheres (20% w/w) 10 mg SA-OMS spheres (20% w/w)
OMS spheres as a DRUG RESERVOIR in saturated solution
SALYCILIC ACID (SA)
SA absorption simulation by substituting solution (0.5 ml) with pure water (0.5 ml) (arbitrary)
0 1 2 mg SA delivered
the reservoir is empty
no reservoir
SA incorporation
SA-OMS
OMS
CREAMS OR OINTMENTS FOR PROLONGED DRUG RELEASE AT CONSTANT CONCENTRATION
Active Principle Ingredient (API)
Liquid A – API soluble
Liquid B – API unsoluble
OMS particles API saturated solution in Liquid A
Liquid A + Liquid B
B. Onida and R. Mortera, Eudermic compositions, WO 2012/007906 A2
e.g. amikacin in water (45%v/v)-glycerole (55%v/v) : 5% w/w API
CREAM, GEL, OINTMENT
Epidermis or mucosa
DRUG-‐OMS
12
Cs: constant (THERAPEUTIC) concentration on the epidermis
DRUG-OMS reservoir
DRUG
SUSTAINED DRUG RELEASE
Department of Applied Science and Technology
CONCLUSIONS ¢ Ordered Mesoporous Silica particles are excellent host
for drug molecules in topical applications, acting as a reservoir in drug delivery.
¢ In contact with a saturated solution of desired therapeutic concentration, they allow to mantein a constant concentration for a controlled time.
¢ Creams, ointments or gels contanining DRUG-OMS can be formulated in order to achieve a sustained release of the drug to epidermis or mucosa, so reducing the number of applications.
¢ The amount of amikacin sulphate absorbed by reconstituted epidermis increases in presence of the DRUG-OMS reservoir.
Department of Applied Science and Technology
ACKNOWLEDGEMENTS Department of Applied Science and Technology
I3P - Innovative Companies Incubator of the Politecnico di Torino
GIORGIO CHIEREGATTI
BEATRICE CAMAROTA
RENATO MORTERA
ANDREA GIGNONE
DARIO CALDAROLA