Cachexia: Pathophysiology and Ghrelin Liposomes for Nose-to-Brain Delivery

Barros, Cecília Torqueti de; Rios, Alessandra Cândida; Alves, Thaís Francine Ribeiro; Batain, Fernando; Crescencio, Kessi; Lopes, Laura J.; Zielińska, Aleksandra; Severino, Patrícia; Mazzola, Priscila Gava; Souto, Eliana B.; Chaud, Marco V.

doi:10.3390/ijms21175974

Cited by 10 publications

(5 citation statements)

References 100 publications

(154 reference statements)

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“…Ghrelin (ghrl) is a 28-amino acid hormone produced primarily in the oxyntic mucosa of the stomach. This hormone binds to growth hormone secretagogue receptor the type 1a (GHS-R1a) in the hypothalamus and stimulates the release of growth hormones after catalyzed by ghrelin-O-acyltransferase (GOAT) [ 4 ]. The ghrelin GOAT system is responsible for regulating energy homeostasis, signaling the hypothalamus’ peripheral nutritional status inducing energy compensations; however, in the body, exogenous ghrelin is subject to very rapid degradation [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The olfactory region of the nasal mucosa provides a connection between the nose and the brain, which can be used to more easily distribute drugs that act on the central nervous system [ 13 ]. In this context, the intranasal release of liposomes loaded with ghrelin to cross the blood-brain barrier and the release of the drug in the central nervous system can be a promising alternative to improve its bioavailability [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration

et al. 2021

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The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration

et al. 2021

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“…Enhancing the ability of ghrelin ligands across the BBB is being explored by researchers [42]. Barros et al found that ghrelin-loaded liposomes greatly improved the efficiency of delivering ghrelin and guaranteed the activity of released ghrelin [43]. In addition, it has been investigated that polymersomes conjugated with UAG are intended to be delivered to the brain across the BBB [38].…”

Section: Ghrelin and Apoptosismentioning

confidence: 99%

Emerging Relevance of Ghrelin in Programmed Cell Death and Its Application in Diseases

Zhang,

Zeng,

Liu

et al. 2023

IJMS

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Ghrelin, comprising 28 amino acids, was initially discovered as a hormone that promotes growth hormones. The original focus was on the effects of ghrelin on controlling hunger and satiation. As the research further develops, the research scope of ghrelin has expanded to a wide range of systems and diseases. Nevertheless, the specific mechanisms remain incompletely understood. In recent years, substantial studies have demonstrated that ghrelin has anti-inflammatory, antioxidant, antiapoptotic, and other effects, which could affect the signaling pathways of various kinds of programmed cell death (PCD) in treating diseases. However, the regulatory mechanisms underlying the function of ghrelin in different kinds of PCD have not been thoroughly illuminated. This review describes the relationship between ghrelin and four kinds of PCD (apoptosis, necroptosis, autophagy, and pyroptosis) and then introduces the clinical applications based on the different features of ghrelin.

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“…21 Despite these advantages, the IN route has some limitations including: short residence time of the administered formulation due to mucociliary clearance, drug degradation by enzymes in the nasal cavity that impair drug delivery to the brain and limit its bioavailability, and limited dosing in terms of volume (50-200 μL) administered in the nasal cavity. 23 Many recent literatures, less than five years, have been published on nose to brain delivery using nanoparticles, to overcome the IN limitations, such as nanoemulsion, 24 polymeric nanoparticles, 25 liposomes, 26 solid lipid nanoparticles (SLNs) 27 or nanostructured lipid carriers (NLCs), 28 which are effective nose-to-brain drug delivery systems that improve the nasal permeability and bioavailability of drugs for effective brain targeting by increasing drug solubility and permeation, reducing mucociliary clearance and enzymatic degradation. 29 In particular, formulations based on nanostructured lipid carriers (NLCs) are interesting candidates for nose to brain drug delivery without any modification to the drug molecule due to their rapid uptake by the brain, bioacceptability, biodegradability and safety.…”

Section: Introductionmentioning

confidence: 99%

Nose to Brain Delivery of Astaxanthin–Loaded Nanostructured Lipid Carriers in Rat Model of Alzheimer’s Disease: Preparation, in vitro and in vivo Evaluation

Shehata¹,

Ismail²,

Kamel³

2023

IJN

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Background Astaxanthin (AST) is a second-generation antioxidant with anti-inflammatory and neuroprotective properties and could be a promising candidate for Alzheimer’s disease (AD) therapy, but is shows poor oral bioavailability due to its high lipophilicity. Purpose This study aimed to prepare and evaluate AST–loaded nanostructured lipid carriers (NLCs), for enhanced nose-to-brain drug delivery to improve its therapeutic efficacy in rat model of AD. Methods AST–NLCs were prepared using hot high-pressure homogenization technique, and processing parameters such as total lipid-to-drug ratio, solid lipid-to-liquid lipid ratio, and concentration of surfactant were optimized. Results The optimized AST–NLCs had a mean particle size of 142.8 ± 5.02 nm, polydispersity index of 0.247 ± 0.016, zeta potential of –32.2 ± 7.88 mV, entrapment efficiency of 94.1 ± 2.46%, drug loading of 23.5 ± 1.48%, and spherical morphology as revealed by transmission electron microscopy. Differential scanning calorimetry showed that AST was molecularly dispersed in the NLC matrix in an amorphous state, whereas Fourier transform infrared spectroscopy indicated that there is no interaction between AST and lipids. AST displayed a biphasic release pattern from NLCs; an initial burst release followed by sustained release for 24 h. AST-NLCs were stable at 4–8 ±2°C for six months. Intranasal treatment of AD-like rats with the optimized AST–NLCs significantly decreased oxidative stress, amyloidogenic pathway, neuroinflammation and apoptosis, and significantly improved the cholinergic neurotransmission compared to AST-solution. This was observed by the significant decline in the levels of malondialdehyde, nuclear factor-kappa B, amyloid beta (Aβ 1‑42 ), caspase-3, acetylcholinesterase, and β-site amyloid precursor protein cleaving enzyme-1 expression, and significant increase in the contents of acetylcholine and glutathione after treatment with AST-NLCs. Conclusion NLCs enhanced the intranasal delivery of AST and significantly improved its therapeutic properties.

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Cachexia: Pathophysiology and Ghrelin Liposomes for Nose-to-Brain Delivery

Cited by 10 publications

References 100 publications

Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration

Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration

Emerging Relevance of Ghrelin in Programmed Cell Death and Its Application in Diseases

Nose to Brain Delivery of Astaxanthin–Loaded Nanostructured Lipid Carriers in Rat Model of Alzheimer’s Disease: Preparation, in vitro and in vivo Evaluation

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