Mucoadhesive nanostructured lipid carriers as a cannabidiol nasal delivery system for the treatment of neuropathic pain

Matarazzo, Ananda Pulini; Elisei, Lívia; Carvalho, Flávia Chiva; Bonfílio, Rudy; Ruela, André Luís Morais; Galdino, Giovane; Pereira, Gislaine Ribeiro

doi:10.1016/j.ejps.2020.105698

Cited by 67 publications

(42 citation statements)

References 50 publications

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“…To that end, a variety of emerging potential therapeutic agents for neuropathic pain are being repositioned or developed for clinical trial. These include monoclonal antibodies against inflammatory mediators, cannabinoids, and inhibitors of G protein-coupled receptors and N-methyl- D -aspartate receptors ( Figure 1B ) ( Karppinen et al, 2003 ; Stahel et al, 2016 ; Jung et al, 2017 ; Wang et al, 2017 ; Aiyer et al, 2018 ; Mapplebeck et al, 2018 ; Kreutzwiser and Tawfic, 2019 ; Alkislar et al, 2020 ; Haleem and Wright, 2020 ; Kushnarev et al, 2020 ; Maayah et al, 2020 ; Yu et al, 2020 ; Zhang W. et al, 2020 ; Matarazzo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

et al. 2021

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Chronic pain has been widely recognized as a major public health problem that impacts multiple aspects of patient quality of life. Unfortunately, chronic pain is often resistant to conventional analgesics, which are further limited by their various side effects. New therapeutic strategies and targets are needed to better serve the millions of people suffering from this devastating disease. To this end, recent clinical and preclinical studies have implicated the epidermal growth factor receptor signaling pathway in chronic pain states. EGFR is one of four members of the ErbB family of receptor tyrosine kinases that have key roles in development and the progression of many cancers. EGFR functions by activating many intracellular signaling pathways following binding of various ligands to the receptor. Several of these signaling pathways, such as phosphatidylinositol 3-kinase, are known mediators of pain. EGFR inhibitors are known for their use as cancer therapeutics but given recent evidence in pilot clinical and preclinical investigations, may have clinical use for treating chronic pain. Here, we review the clinical and preclinical evidence implicating EGFR in pathological pain states and provide an overview of EGFR signaling highlighting how EGFR and its ligands drive pain hypersensitivity and interact with important pain pathways such as the opioid system.

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Section: Introductionmentioning

confidence: 99%

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

et al. 2021

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“…This synergism explains the reduction in opioid dosage when used in combination with cannabinoids. THC is capable of reducing the minimum effective dose of morphine by 55%, methadone by 75% and codeine by 96% [ 52 ]. On the other hand, the cannabinoid system is larger and occupies more brain areas than the opioid system.…”

Section: Pain and Role Of Cannabinoidsmentioning

confidence: 99%

“…Recently, the role of the entourage effect of cannabis-based products in pain has been evaluated. Although definitive studies are still required, there is increasing evidence to support the beneficial effects of plant-derived cannabinoids in providing pain relief [ 52 ].…”

Section: Galenic Preparations Of Cannabis Extractsmentioning

confidence: 99%

“…NLCs provide an increase in the loading capacity of active agents in the nanoparticles and avoid leakage during storage. Although some works have described the potentiality of this carrier strategy, only a few works, which have exploited the mucoadhesive properties for nasal delivery, have recently been found [ 52 , 212 ]. Matarazzo et al have described the preparation, characterisation and in vivo nociceptive activity of NLCs loaded with CBD [ 52 ].…”

Section: Pharmaceutical-grade Cannabinoid Formulationsmentioning

confidence: 99%

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Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

Stella

Baratta

Pepa

et al. 2021

Drugs

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The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.

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“…In this sense, several approaches have been considered to overcome the limitations of this route and improve the analgesic effect of non-controlled central- and systemic-acting analgesic agents. These include the use of absorption enhancers formulated in various pharmaceutical forms, such as in situ and chitosan hydrogels, mucoadhesive nanostructured lipid carriers and chitosan nanoparticles [ 13 , 14 , 15 , 16 ]. However, some of these approaches may lead to nasal toxicity and leaching of membrane components including proteins and enzymes, which may cause local irritation to the nasal mucosa [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems

et al. 2021

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Nasal nanovesicular delivery systems (NVS) containing the noncontrolled analgesic drugs Ketoprofen, Butorphanol or Tramadol, incorporated in a phospholipid nanovesicular carrier, were designed and investigated. The systems were first characterized for their physicochemical properties. Due to their composition, comprising propylene glycol as a lipid bilayers fluidizer, these systems contain soft vesicles. Pharmacokinetic profiles of Tramadol in plasma and brain and of Ketoprofen in plasma were also assessed. The analgesic effect of each of the three tested drugs was evaluated in the acetic acid mice model for pain. One important result obtained in this work is that the concentration of Tramadol in rats’ plasma and brain increased rapidly after administration, reaching a peak value 10 min after administration with a Cmax of 2 to 5 folds greater than that for the oral or nasal non-vesicular treatments, respectively. In the case of Ketoprofen, the peak of the drug level in plasma was measured 10 min post nasal administration in NVS. The Cmax was three-fold higher relative to oral administration of this drug. In the experiment testing analgesia, a rapid and improved analgesia was observed for the tested drugs when delivered nasally in the nanocarrier. On the other hand, a weaker analgesic effect was observed for oral and nasal control systems. This new approach suggests that nasal delivery of non-controlled drugs in soft nanovesicles may open the way for better and noninvasive treatment of severe pain.

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Mucoadhesive nanostructured lipid carriers as a cannabidiol nasal delivery system for the treatment of neuropathic pain

Cited by 67 publications

References 50 publications

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems

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