Enhanced intradermal delivery of ivermectin using the ......School of Pharmacy Queen’s University...
Transcript of Enhanced intradermal delivery of ivermectin using the ......School of Pharmacy Queen’s University...
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ANDI DIAN PERMANAPhD Student
School of PharmacyQueen’s University Belfast
Enhanced intradermal delivery of ivermectinusing the combination of nanosuspensions and
dissolving microneedles as a therapy for lymphatic filariasis
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LYMPHATIC FILARIASIS (LF)Caused by
Wuchereriabancrofti
Brugia malayi
Brugia timori
Neglected tropical disease in 52
countries Affecting 886 million
people worldwide
Oral administration of ivermectin (IVM)
INTRODUCTION
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Effective to kill microfilariae in blood stream
Fail to kill adult filarial worms in lymph node
Ineffective therapy of LF
INTRODUCTION
DrugBlood
LogP < 5
LogP > 5
Enterocyte
Lymph
LogP = 4.8
IVERMECTINE
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• Nanoparticle with sizes of 10-100 nm
• Intradermal delivery of nanoparticles
Intradermal injection
Painful
Unreliable
Hazard clinical waste
Less administration volume
INTRODUCTION
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• Dissolving microneedles as innovative approach for intradermal delivery
• Painless
• Self-applicable
• No clinical waste
• More administration volume (larger patches)
INTRODUCTION
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1. Formulation and optimisation of nanosuspension
2. Characterisation of nanosuspension
3. Formulation and characterisation of dissolving microneedle
4. Dermatokinetic and skin drug distribution studies
EXPERIMENTAL DESIGN
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NANOSUSPENSION PREPARATION
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Particle size: 98.12 ± 7.76 nm
PDI: 0.233 ± 0.02
Zeta potential: -15.07 ± 0.95
NANOSUSPENSION OPTIMISATION
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Spherical NS(TEM)
No chemical interactions(FTIR)
Changed from crystalto amorphous(DSC)
Increase cumulative release after 24 h
200 nm
NANOSUSPENSION CHARACTERISATIONS
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MICRONEEDLE PREPARATION
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MNs-NS exhibited homogenous MNs and had sharp tips 370.17 ± 17.13 µm of needles were inserted into
Parafilm®M (skin stimulant) 369.22 ± 13.93 µm of needles were inserted into full-
thickness porcine skin
MICRONEEDLE CHARACTERISATIONS
Optical coherence tomography images in Parafilm®M (a)and porcine skin (b)
a b
1 mm
0.5 mm
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Epidermis Dermis
Dermatokinetic parameters (MNs)AUC0-24
(µg/cm3/h)tmax(h)
Cmax(µg/cm2)
Epidermis 2018.92 ± 342.32 1.37 ± 0.29 108.02 ± 19.71Dermis 7122.40 ± 784.09 8.01 ± 1.23 372.07 ± 49.98
Dermatokinetic parameters (Needle-free patch)AUC0-24
(µg/cm3/h)tmax(h)
Cmax(µg/cm3)
Epidermis 333.01 ± 73.21 4.35 ± 0.86 15.11 ± 3.05Dermis 33.63 ± 6.83 11.51 ± 3.34 1.72 ± 0.55
The values of Cmax and AUC0-24 inthe dermis was found to besignificantly higher (p < 0.05) thanin epidermis
The values of Cmax and AUC0-24 ofdrugs after MNs application weresignificantly higher (p < 0.05) thanneedle-free patch application inepidermis and dermis
DERMATOKINETIC STUDY
Considering the drug amountin the actual needles of thearrays, 34.54 ± 4.98% of IVMwere retained in the dermisafter 24 h administration.
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DISCUSSION
IVM NanosuspensionFree IVM
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• Nanosuspension of IVM was successfully developed and optimisedusing central composite design to achieve the requirement oflymphatic uptake
• The incorporation of nanosuspension into MN arrays significantlyimprove the delivery of IVM into the dermis
• Further studies are required to determine the concentrations of drugswhich reach the infection site in vivo
CONCLUSIONS
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Professor Ryan F. Donnelly
Microneedle Research Group
Indonesia Endowment Fund for Education (LPDP) Scholarship
Hasanuddin University, Indonesia
ACKNOWLEDGMENTS