Development of Meloxicam-Human Serum Albumin Nanoparticles for Nose-to-Brain Delivery via Application of a Quality by Design Approach

Katona, Gábor; Balogh, György Tibor; Dargó, Gergő; Gáspár, Róbert; Márki, Árpád; Ducza, Eszter; Sztojkov‐Ivanov, Anita; Tömösi, Ferenc; Kecskeméti, Gábor; Janáky, Tamás; Kiss, Tamás; Ambrus, Rita; Pallagi, Edina; Szabó‐Révész, Piroska; Csóka, Ildikó

doi:10.3390/pharmaceutics12020097

Cited by 36 publications

(21 citation statements)

References 48 publications

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“…Liposomes as lipid-based nanoDDS with reduced particle size and the bilayer lipid membrane provided high and fast transport of encapsulated lamotrigine through the nasal mucosa [17]. The in vivo studies of meloxicam (MEL)-containing human serum albumin nanoparticles corroborated the in vitro dissolution and permeability studies contributed to determine the criteria of trans-epithelial and axonal transport ensuring higher cerebral concentration of the API [18]. These results gave the background of the investigation of polymeric micelles, which may offer more favorable pharmacokinetics and higher protection to the API.…”

Section: Introductionmentioning

confidence: 90%

“…In vitro permeability study of MEL-loaded polymeric micelles in triplicate compared to crystalline MEL; data are means ± SD (n = 3 independent formulations). To estimate the statistical in vivo brain distribution of MEL-containing polymeric micelles IVIVC was performed applying in vitro and in vivo data of previous experiments, namely a MEL suspension, MEL-containing human serum albumin nanoparticles with Tween-20 (MEL-HAS-Tween) and without surfactant (MEL-HAS) [18] as well as a MEL-containing nanosuspension [27]. These formulations contained MEL in the same concentration.…”

Section: In Vitro Nasal Diffusion Studymentioning

confidence: 99%

“…It has poor water solubility (BCS class II), especially in the pH range of the nasal cavity, which impedes liberation from the formulation, resulting in low absorption as well as bioavailability [26]. By encapsulating MEL in a polymeric micelle, the drug could be absorbed by the nasal epithelial cells, thereby delivering it directly through axonal transport pathway into the CNS [18,27].…”

Section: Introductionmentioning

confidence: 99%

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Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

et al. 2020

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Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

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Section: Introductionmentioning

confidence: 90%

Section: In Vitro Nasal Diffusion Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

et al. 2020

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“…Anti-inflammatory agents such as meloxicam (MEL) (Figure 8), a selective cyclooxygenase 2 (COX-2) inhibitor, are effective to neuroinflammation in AD. MEL-loaded albumin nanoparticles showed a higher cerebral concentration of MEL through intranasal administration in an in vivo assay using rats, compared to intravenous administration [55]. Thus, this system based on albumin-based nanoparticles can be applied for intranasal insulin delivery.…”

Section: Intranasal Administration Using Nanoparticlesmentioning

confidence: 90%

Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Tashima

2020

Molecules

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The direct delivery of central nervous system (CNS) drugs into the brain after administration is an ideal concept due to its effectiveness and non-toxicity. However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. Thus, alternative approaches must be developed. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Nonetheless, intranasally administered insulin was delivered into the brain. Therefore, insulin conjugates with covalent or non-covalent cargos, such as AD or other CNS drugs, could potentially contribute to a promising strategy to cure CNS-related diseases. In this review, I will introduce the CNS drug delivery approach into the brain using nanodelivery strategies for insulin through transcellular routes based on receptor-mediated transcytosis or through paracellular routes based on escaping the tight junction at the olfactory epithelium.

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“…It is noteworthy that in this way the BBB is bypassed [ 1 , 31 ]. Therefore, molecular mass of the drug in this case is less important for the absorption process, and it has been reported that both small [ 32 , 33 ] and large molecules [ 34 , 35 ] can be successfully delivered in this way. However, despite numerous interesting features, there are also several drawbacks related to this administration route.…”

Section: Introductionmentioning

confidence: 99%

Microemulsion-Based Media in Nose-to-Brain Drug Delivery

et al. 2021

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Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system. The most important advantage of this approach is the ability to avoid the blood–brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system. Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy. The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa. These issues could be minimized by using a properly designed drug carrier. Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes. The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia.

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Development of Meloxicam-Human Serum Albumin Nanoparticles for Nose-to-Brain Delivery via Application of a Quality by Design Approach

Cited by 36 publications

References 48 publications

Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration

Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Microemulsion-Based Media in Nose-to-Brain Drug Delivery

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