Nasal biocompatible powder of Geraniol oil complexed with cyclodextrins for neurodegenerative diseases: physicochemical characterization and in vivo evidences of nose to brain delivery

Truzzi, Eleonora; Rustichelli, Cecilia; Oliveira, Edilson Ribeiro de; Ferraro, Luca; Maretti, Eleonora; Graziani, Daniel; Botti, Giada; Beggiato, Sarah; Iannuccelli, Valentina; Lima, Eliana Martins; Dalpiaz, Alessandro; Leo, Eliana Grazia

doi:10.1016/j.jconrel.2021.05.020

Cited by 21 publications

(12 citation statements)

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“…Moreover, chitosan appears to transiently increase the permeability of mucosa by opening their tight junctions [29]. Taking into account these aspects, nasal formulations based on micro or nanoparticulate systems able to produce high dissolution rates of neuroactive drugs or prodrugs were designed; in these formulations, the presence of chitosan appeared important in inducing their efficient delivery in the CNS [30][31][32][33][34][35][36][37][38][39][40][41].…”

Section: Nasal Formulations and The Role Of Cds As Modulators Of The Drug Absorptionmentioning

confidence: 99%

“…Singularly, the nasal administration of the geraniol/β-CD suspension allowed to obtain geraniol amounts in CSF of rats two orders of magnitude higher than those obtained by using the geraniol/HP-β-CD solution. This result was attributed to the potential aptitude of geraniol/β-CD complex to form nanoparticulate aggregates able to reduce the interaction of geraniol with mucus, allowing a direct deposition of the drug on the olfactory mucosa [41].…”

Section: Nasal Formulations and Cds Modulation Of Systemic And Central Absorption Of Neuroactive Agentsmentioning

confidence: 99%

“…As a consequence, most studies evaluating the impact of CDs on nose-to-brain drug delivery were carried out in rats [41,57,69,74]. Usually, intranasal drug administration is performed on anaesthetized rats either for ethical reasons or to avoid (i) damaging the nasal mucosa with the drug delivery device; and (ii) losing part of the administered dose.…”

Section: Combining Intranasal Administration With Plasma and Cerebrospinal Fluid Sample Collections: Useful Strategies To Evaluate Nose-tmentioning

confidence: 99%

“…To intranasally administer the required drug amount, the anesthetized rat is placed on its back or in the right lateral recumbency [39,57], and the drug is administered by introducing into one or each nostril the required microliters of the formulation under investigation. To avoid incidental damage of nasal mucosa and to be sure to precisely administer the required volume, the use of a semiautomatic pipet attached to a short polyethylene tubing inserted approximately 0.5-0.7 cm into each nostril is suggested [39,41]. After that, biological fluid sample collection can also be performed on the awake, freely moving animal.…”

Section: Combining Intranasal Administration With Plasma and Cerebrospinal Fluid Sample Collections: Useful Strategies To Evaluate Nose-tmentioning

confidence: 99%

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Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

et al. 2021

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Cyclodextrins (CDs) are oligosaccharides widely used in the pharmaceutical field. In this review, a detailed examination of the literature of the last two decades has been made to understand the role of CDs in nasal drug delivery systems. In nasal formulations, CDs are used as pharmaceutical excipients, as solubilizers and absorption promoters, and as active ingredients due to their several biological activities (antiviral, antiparasitic, anti-atherosclerotic, and neuroprotective). The use of CDs in nasal formulations allowed obtaining versatile drug delivery systems intended for local and systemic effects, as well as for nose-to-brain transport of drugs. In vitro and in vivo models currently employed are suitable to analyze the effects of CDs in nasal formulations. Therefore, CDs are versatile pharmaceutical materials, and due to the continual synthesis of new CDs derivatives, the research on the new nasal applications is an interesting field evolving in the coming years, to which Italian research will still contribute.

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Section: Nasal Formulations and The Role Of Cds As Modulators Of The Drug Absorptionmentioning

confidence: 99%

Section: Nasal Formulations and Cds Modulation Of Systemic And Central Absorption Of Neuroactive Agentsmentioning

confidence: 99%

Section: Combining Intranasal Administration With Plasma and Cerebrospinal Fluid Sample Collections: Useful Strategies To Evaluate Nose-tmentioning

confidence: 99%

Section: Combining Intranasal Administration With Plasma and Cerebrospinal Fluid Sample Collections: Useful Strategies To Evaluate Nose-tmentioning

confidence: 99%

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Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

et al. 2021

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“…To direct OZ to the brain through the bypass of BBB, and to minimize its systemic side effects, the nasal pathway is recommended [18][19][20]. Nasal mucosa (in the nasal cavity) is a highly permeable membrane that is widely used as a non-invasive approach to bypass the BBB [18].…”

Section: Introductionmentioning

confidence: 99%

Utilization of Polymeric Micelles as a Lucrative Platform for Efficient Brain Deposition of Olanzapine as an Antischizophrenic Drug via Intranasal Delivery

et al. 2022

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Schizophrenia is a mental disorder characterized by alterations in cognition, behavior and emotions. Oral olanzapine (OZ) administration is extensively metabolized (~up to 40% of the administrated dose). In addition, OZ is a P-glycoproteins substrate that impairs the blood–brain barrier (BBB) permeability. To direct OZ to the brain and to minimize its systemic side effects, the nasal pathway is recommended. OZ-loaded polymeric micelles nano-carriers were developed using suitable biodegradable excipients. The developed micelles were physicochemically investigated to assess their appropriateness for intranasal delivery and the potential of these carriers for OZ brain targeting. The selected formula will be examined in vivo for improving the anti-schizophrenic effects on a schizophrenia rat model. The binary mixture of P123/P407 has a low CMC (0.001326% w/v), which helps in maintaining the formed micelles’ stability upon dilution. The combination effect of P123, P407 and TPGS led to a decrease in micelle size, ranging between 37.5–47.55 nm and an increase in the EE% (ranging between 68.22–86.84%). The selected OZ–PM shows great stability expressed by a suitable negative charge zeta potential value (−15.11 ± 1.35 mV) and scattered non-aggregated spherical particles with a particle size range of 30–40 nm. OZ–PM maintains sustained drug release at the application site with no nasal cytotoxicity. In vivo administration of the selected OZ–PM formula reveals improved CNS targeting and anti-schizophrenia-related deficits after OZ nasal administration. Therefore, OZ–PM provided safe direct nose-to-brain transport of OZ after nasal administration with an efficient anti-schizophrenic effect.

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Microwave-assisted enzymatic synthesis of geraniol esters in solvent-free systems: optimization of the reaction parameters, purification and characterization of the products, and biocatalyst reuse

et al. 2023

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Various geraniol esters act as insect pheromones and display pharmacological activities, especially as neuroprotective agents. Therefore, the search for synthetic strategies alternative to traditional chemical synthesis could help designing ecofriendly routes for the preparation of such bioactive compounds. Hence, this work aims at the microwave-assisted enzymatic synthesis of geranyl esters in solvent-free systems. The process variables were optimized for the synthesis of geranyl acetoacetate, achieving 85% conversion after 60 min using a 1:5 substrates molar ratio (ester to geraniol), 80 °C and 8.4% of Lipozyme 435 lipase without removal of the co-produced methanol. On the other hand, a 95% conversion was reached after 30 min using 1:6 substrates molar ratio, 70 °C and 7% lipase in the presence of 5Å molecular sieves for the methanol capture. In addition, the lipase showed good reusability, maintaining the same activity for five reaction cycles. Finally, under the above optimized conditions, other geraniol esters were successfully synthetized such as the geranyl butyrate (98%), geranyl hexanoate (99%), geranyl octanoate (98%), and geranyl (R)-3-hydroxybutyrate (56%). These results demonstrate the microwave-assisted lipase-catalyzed transesterification in a solvent-free system as an excellent and sustainable catalytic methodology to produce geraniol esters. Graphical Abstract

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Nasal biocompatible powder of Geraniol oil complexed with cyclodextrins for neurodegenerative diseases: physicochemical characterization and in vivo evidences of nose to brain delivery

Cited by 21 publications

References 50 publications

Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

Versatile Nasal Application of Cyclodextrins: Excipients and/or Actives?

Utilization of Polymeric Micelles as a Lucrative Platform for Efficient Brain Deposition of Olanzapine as an Antischizophrenic Drug via Intranasal Delivery

Microwave-assisted enzymatic synthesis of geraniol esters in solvent-free systems: optimization of the reaction parameters, purification and characterization of the products, and biocatalyst reuse

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