Abstract
Possible risk of leukopenia is one of the drug-induced adverse effects of the atypical antipsychotic agent olanzapine (OLZ). Hence, to prevent the peripheral exposure and related side effects of the agent, the present research was aimed to prepare and investigate safety and efficacy of OLZ-loaded lipid nanocarriers in the therapy of CNS disorders via intranasal (i.n.) delivery. The OLZ-loaded nanostructured lipid carriers (NLC) and microemulsion (ME) were prepared by melt emulsification and aqueous titration methods, respectively. Optimized formulation was evaluated for the particle size, zeta potential and entrapment efficiency were found to be 88.95 ± 0.8 and 24.80 ± 0.5 nm, -22.21 ± 1.9 and − 20.84 ± 1.3 mV, and 88.94 ± 1.6 and 98.40 ± 0.95%, respectively for the two nanocarriers (NLC and ME). Alternatively, ex vivo permeation of OLZ mucoadhesive NLC (OLZ-MNLC) and OLZ mucoadhesive ME (OLZ-MME) was observed 820 ± 7.2 and 940 ± 8.9 µg/cm2, respectively. Finally, Cmax values calculated for OLZ in brain through administration of 99MTc-OLZ-MNLC (i.n.), 99MTc-OLZ-MME (i.n.) and 99MTc-OLZ-NLC (i.v.) and it was found to 9.33 ± 0.65% radioactivity/gram (RA/g), 1.06 ± 0.26% RA/g and 0.082 ± 0.004% RA/g, respectively. Therefore, 99MTc-OLZ-MNLC formulation through i.n. delivery showed superior brain uptake than OLZ-MME formulation. Simultaneously, the nanoformulations didn’t reflect any gross changes in biomarkers and hematological toxicity when compared with control. Hence, it can be inferred that the nose-to-brain delivery of OLZ-MNLC can be considered as effective and safe delivery for brain therapy.
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Acknowledgements
The author (Dnyandev Gadhave) expresses his wholehearted gratitude and appreciation to Savitribai Phule Pune University (SPPU), for financial support to complete this project in form of research stipend (Ref/2829). Authors would like to thanks, ACTREC Kharghar, Mumbai for their kind support in gamma scintigraphy.
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All animals required for this study were approved by institutional animal ethics committee of ACTREC Kharghar, Mumbai, India, (Protocol No. ACTREC/IAEC/12/2015) and Sinhgad Institute of Pharmacy, Pune, India, regulated by CPCSEA (Protocol No. SIOP/IAEC/2017/02/13).
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Gadhave, D., Choudhury, H. & Kokare, C. Neutropenia and leukopenia protective intranasal olanzapine-loaded lipid-based nanocarriers engineered for brain delivery. Appl Nanosci 9, 151–168 (2019). https://doi.org/10.1007/s13204-018-0909-3
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DOI: https://doi.org/10.1007/s13204-018-0909-3