Fabrication of nanoemulsion loaded with cefuroxime for efficient translocation across the blood brain barrier
Meningitis is one of the commonest and most debilitating acute neurological conditions. Drugs that are effective against diseases in the central nervous system and reach the brain via the blood compartment must pass the blood brain barrier (BBB), the unique interface that formed protection aga...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/69664/1/fpsk%202018%2022%20ir.pdf |
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| Summary: | Meningitis is one of the commonest and most debilitating acute neurological
conditions. Drugs that are effective against diseases in the central nervous
system and reach the brain via the blood compartment must pass the blood
brain barrier (BBB), the unique interface that formed protection against
potentially harmful molecules. Antibiotics in high doses had been used to treat
this illness however, with significant increase in side effects. Nanoemulsion
was an effective drug nanocarrier due to their biocompatibility, relative stability,
high drug loading capacity, preserved cytotoxicity and ability to protect drugs
from hydrolysis and enzymatic degradation in physiologic conditions.
In this research, a nanosystem for blood-brain barrier translocation utilizing
nanoemulsions loaded with cefuroxime were developed. This new form of drug
delivery will be able to reduce the peripheral side effects of the cefuroxime and
at the same time increase the penetration across the BBB. Optimization,
characterization and stability evaluation were perfomed to ensure the
formulated nanoemulsion fulfilled the requirement for parenteral drug delivery.
The characterization revealed particle size of 100.32 ± 0.75 nm, polydispersity
index of 0.18 ± 0.01, zeta potential of −46.9 ± 1.39 mV, viscosity of 1.24 ± 0.34
cps and osmolality of 285.33 ± 0.58 mOsm/kg, indicating the nanoemulsion
compatibility for parenteral application.
Cefuroxime loaded nanoemulsion (CLN) was subjected to in vitro and in vivo
studies. A humanized in vitro model of blood brain barrier based on cocultures
of human microvascular endothelial cells (hCMEC/D3) and normal human
astrocyte (NHA) was developed. This model was validated to ensure it closely
resemble the microenvironment condition of blood brain barrier. This model
was used to evaluate the penetration efficiency of cefuroxime loaded nanoemulsion. The in vitro study showed that the formulated CLN has higher
apparent permeability (0.04 ± 0.01 cm/h) when compared to cefuroxime
solution (0.02 ± 0.02 cm/h). The pharmacokinetic profile generated from in vivo
study revealed that CLN was successfully improved the plasma and brain
concentration of cefuroxime when compared to cefuroxime solution. From the
results obtained, drug loaded nanoemulsion could be an effective carrier for
drug delivery across the brain. |
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