Neutropenia and leukopenia protective intranasal olanzapine-loaded lipid-based nanocarriers engineered for brain delivery

• Published in: Applied nanoscience Vol. 9; no. 2; pp. 151 - 168
• Main Authors: Gadhave, Dnyandev, Choudhury, Hira, Kokare, Chandrakant
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2019; Springer Nature B.V
• Subjects: Biomarkers; Brain; Chemistry and Materials Science; Drug delivery systems; Entrapment; Leukopenia; Lipids; Materials Science; Membrane Biology; Nanochemistry; Nanotechnology; Nanotechnology and Microengineering; Original Article; Radioactivity; Side effects; Therapy; Titration; Toxicity; Zeta potential; Nanostructured lipid carriers; In vivo hematology; Drug-induced agranulocytosis; Tc radioisotope; Microemulsion; Brain availability
• ISSN: 2190-5509; 2190-5517
• DOI: 10.1007/s13204-018-0909-3

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/cm 2 , respectively. Finally, C max values calculated for OLZ in brain through administration of 99M Tc-OLZ-MNLC (i.n.), 99M Tc-OLZ-MME (i.n.) and 99M Tc-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, 99M Tc-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.