Devices for osteoarthritis symptoms treatment: a patent review.

INTRODUCTION: Osteoarthritis is a musculoskeletal disease that can lead to the loss and inability of those affected to perform normal daily functions, which leads to a decrease in quality of life. The main symptoms of osteoarthritis are tenderness, joint pain, stiffness, crepitus, limited movement, and local inflammation. AREAS COVERED: The selected patents were deposited from 2010 to April 2022 involving 57 documents that were in line with the study objective in the final selection. The patents were classified in years, country, and applicants. Also, the therapeutic fields that presented the most documents were electrical stimulation, phototherapy, and ultrasound, followed by magnetic, electromagnetic, and thermotherapy. Therefore, the most current therapies used in the documents are already on the market. EXPERT OPINION: Although the OA is cureless, non-surgical treatments are classified as the primary management approach for this disease. The pharmacological and non-pharmacological therapies are employed to reduce its prevalence and ensure the effectiveness of treatments. A strategy for relieving OA symptoms is non-pharmacological treatment, which can be based on exercise and patient education, combined with other alternative therapies. These therapies are used as supplements to the main OA treatments, enhancing the effectiveness of treatment outcomes.

Is imiquimod a promising drug to treat oral mucosa diseases? A scoping review and new perspectives.

Imiquimod (IMQ) is a chemotherapeutic and immunostimulant drug that is applied topically, demonstrating antitumor and antiviral activities. The objective of this review was to compile data on the off-label use of IMQ in oral mucosal diseases. IMQ has exhibited effectiveness in the treatment of various oral mucosal conditions, including oral carcinogenic lesions, neoplasms, HPV-related lesions and autoimmune disorders. Although IMQ holds promise as a potential strategy for addressing oral mucosal lesions, it is important to note that significant side effects have been frequently reported. Nonetheless, it is crucial to develop and test new technological systems, such as the combination of nanotechnology with innovative drug delivery platforms. These advancements aim to minimize side effects and prolong the drug's contact time with the mucosa, preventing its removal by salivary flow.

Synthesis of films based on chitosan and protic ionic liquids to be used as wound dressing on the oral mucosa.

Oral mucosal ulcerations expose connective tissue to different pathogens and this can progress to systemic infection. This study aimed to synthesize environmentally-friendly films with chitosan and protic ionic liquids, possessing mucoadhesive properties, activity against opportunistic microorganisms, enhanced malleability and mechanical resistance to be used as a wound dressing on the oral mucosa. Therefore, films with chitosan and 10, 35, and 50 % (wt/wt) of 2-hydroxy diethylammonium lactate, salicylate, and maleate protic ionic liquids were synthesized. Thickness measurements and mechanical properties analysis were performed. In addition, oral mucoadhesion, antimicrobial activity, and cytotoxicity properties were investigated. Results showed that the addition of 35wt% and 50wt% of all kinds of protic ionic liquids tested presented significant improvements in film thickness and mechanical properties. Films based on chitosan and the protic ionic liquid 2-hydroxy diethylammonium salicylate at percentages of 35 and 50wt% exhibited superior mucoadhesive properties, antimicrobial activity on opportunistic microorganisms and an improvement in their flexibility after immersion in synthetic saliva. Cytotoxicity results suggest that all kinds of chitosan/protic ionic liquids films tested are safe for intra-oral use. Therefore, the results of this study indicate that these materials could be good candidates for efficient and environmentally-friendly wound dressing films on the oral mucosa.

The management of osteoarthritis symptomatology through nanotechnology: a patent review.

Osteoarthritis is considered a degenerative joint disease that is characterised by inflammation, chronic pain, and functional limitation. The increasing development of nanotechnology in drug delivery systems has provided new ideas and methods for osteoarthritis therapy. This review aimed to evaluate patents that have developed innovations, therapeutic strategies, and alternatives using nanotechnology in osteoarthritis treatment. The results show patents deposited from 2015 to November 2021 in the online databases European Patent Office and World Intellectual Property Organisation. A total of 651 patents were identified for preliminary assessment and 16 were selected for full reading and discussion. The evaluated patents are focused on the intraarticular route, oral route, and topical route for osteoarthritis treatment. The intraarticular route presented a higher patent number, followed by the oral and topical routes, respectively. The development of new technologies allows us to envision a promising and positive future in osteoarthritis treatment.

Chemoprevention in oral leukoplakia: challenges and current landscape.

Oral potentially malignant disorders have the potential to transform into oral cancer. Oral leukoplakia is a prevalent OPMD with a 9.8% malignant transformation rate. The standard management for OL involves surgical excision, but its efficacy in preventing clinical recurrence and malignant transformation is limited. Therefore, alternative strategies such as chemoprevention modalities have emerged as a promising approach to inhibit the carcinogenesis process. The aim of this review was to identify human studies that investigated the effectiveness of chemopreventive agents in preventing the progression of oral leukoplakia and to provide guidance for future research. Several systemic and topical agents have been evaluated for their potential chemopreventive effects in oral leukoplakia. Systemic agents that have been investigated include vitamin A, lycopene, celecoxib, green tea extract, ZengShengPing, Bowman Birk inhibitor, beta-carotene, curcumin, erlotinib, and metformin. In addition, topical agents tested include bleomycin, isotretinoin, ONYX-015 mouthwash, ketorolac, and dried black raspberry. Despite numerous agents that have already been tested, evidence supporting their effectiveness is limited. To improve the search for an ideal chemopreventive agent for oral leukoplakia, we propose several strategies that can be implemented. Oral leukoplakia chemoprevention presents a promising opportunity for decreasing the incidence of oral cancer. Identifying new chemopreventive agents and biomarkers for predicting treatment response should be a focus of future research.

Antibacterial drugs and cyclodextrin inclusion complexes: a patent review.

INTRODUCTION: Bacterial antibiotic resistance occurs when bacteria mutate and escape the effect of antibiotics, which makes the antibiotics no longer effective in treating infections. New solutions for bacterial infections are a persistent need including the identification of drugs with better pharmacological profiles, more potent, and safer. Cyclodextrins inclusion complexes have been able to improve the physicochemical and pharmacological properties of the formulation molecules, resulting in new alternatives with better efficacy. AREAS COVERED: The patents analyzed in the review used treatments based on antibiotics already on the market, natural products, and synthesized molecules composed of the formulation with cyclodextrins. The combination between cyclodextrin and nanostructures also were presented in the patents review process. Moreover, inclusion complexes have been an alternative in developing treatment mainly in China by the pharmaceutical industries in several countries such as Germany, Hungary, the United States of America, Japan and China. EXPERT OPINION: This review is broad and complete since it considers the first patent involving cyclodextrins and antibacterial drugs. Therefore, the various inclusion complexes and antibacterial drugs alternatives presented in this review offer therapeutic options to fight bacterial infections. If shown to be effective, these drugs may be extremely important in the current clinical practice.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Evaluation of an Efficient and Skin-Adherent Semisolid Sunscreen Nanoformulation.

INTRODUCTION: Sunscreens are substances applied on the skin surface to protect the skin from the harmful effects of UV light. Nanoparticles can increase the retention time of the sunscreen on the skin surface and its efficacy, by acting as physical barriers. The present investigation aimed to evaluate the influence of the chitosan coating of benzophenone-3-loaded lipid-core nanocapsules (CH-LCN) on the skin adhesion and photoprotective effect of the sunscreen. METHODS: CH-LNC were obtained by the interfacial deposition of preformed polymer. A suitable semisolid formulation was obtained by using hydroxyethyl cellulose as the gel-forming polymer. Skin adhesion experiments were performed in vitro by applying the formulation on porcine skin and keeping it under water at 32 °C for up to 60 min. Photoprotective effect was analyzed in vitro by the capacity of the formulations to protect a photo unstable substance (resveratrol) from degradation under UV light. RESULTS: CH-LNC presented size of around 150 nm, with low polydispersity, positive zeta potential, due to chitosan, and benzophenone-3 encapsulation efficiency of close to 100% (3 mg/mL). The proposed gel presented suitable consistence and pH for skin application and benzophenone-3 concentration of around 3 mg/g. Although coated and uncoated lipid-core nanocapsules increased benzophenone-3 skin adhesion after 10 min of water immersion, only the nanoparticles coated with chitosan were able to do so after 60 min. The chitosan coating of the nanocapsules increased the photoprotection of the sunscreen under UVA and UVB light after 60 min of exposure, probably due to the film-forming properties of chitosan. CONCLUSION: The chitosan coating of CH-LCN increased the skin adhesion and the photoprotective effect of the sunscreen.

Mapping of New Pharmacological Alternatives in the Face of the Emergence of Antibiotic Resistance in COVID-19 Patents Treated for Opportunistic Respiratory Bacterial Pathogens.

BACKGROUND: The increase in bacterial resistance against antibiotics is thought to be another type of pandemic after COVID-19. Emergency treatment based on antibiotics is a major influence in increasing this resistance. Bacteria, such as Klebsiella pneumoniae, are the most affected by the indiscriminate use of antibiotics, since they are resistant to most antibiotics currently available on the market. OBJECTIVE: This review aimed to evaluate patents of new drugs and formulations, for the treatment of infections caused by Klebsiella pneumoniae. METHODS: The present patent review was carried out through a specialized search database Espacenet. The selection was based on the criteria of patents published from 2010 to May 2021, in any language, and containing the keywords in title or abstract. Also, a research was performed on the PubMed database, using the inclusion criteria. RESULTS: Twenty-two patents were selected for the analysis according to the aim of the study. The advance of new patents has been mostly observed in the World Intellectual Property Organization, China, and United States. The results showed that the main approach was the drug association, followed by drug carriers, new isolated products, and vaccines. CONCLUSION: It has been observed that few studies use new drug alternatives for the treatment, probably due to the higher cost of the development and lack of investments. The effectiveness and safety of these therapies depend on the acceptance, the correct prescription, and rational use of medicines. Therefore, this review can further develop new treatments as alternatives against Klebsiella pneumoniae and pneumonia caused by it.

Pharmaceuticals agents for preventing NSAID-induced gastric ulcers: a patent review.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs widely used due to their pharmacological potential, demonstrating anti-inflammatory, analgesic, or antipyretic activity. However, prolonged use of these medications can lead to the development of gastric ulcers in patients. This review aimed to find patents for drugs with an anti-inflammatory and gastroprotective character to treat NSAID-induced gastric ulcers. AREAS COVERED: For the treatment of NSAID-induced gastric ulcers, formulations with different action mechanisms were found, including donors of nitric oxide, heterocyclic compounds, and natural products. EXPERT OPINION: Many of the structures found have already been used in clinic settings and others, and according to the results found, they are promising for the treatment of gastric ulcers.

Mapping the technological landscape of SARS, MERS, and SARS-CoV-2 vaccines.

PURPOSE: The last two decades have seen the emergence of several viral outbreaks. Some of them are the severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome 2 (SARS-CoV2) - the cause of the coronavirus disease 2019 (COVID-19). Ever, vaccines for emergency use have been authorized for the control and prevention of COVID-19. Currently, there is an urgent need to develop a vaccine for prophylaxis of COVID-19 and for other future epidemics. METHODS: This review describes patented vaccines for SARS and MERS-CoV and vaccines developed and approved for emergency use against the new coronavirus (COVID-19). The European Patent Office and the World Intellectual Property Organization were the patent databases used using specific terms. In addition, another search was carried out in the Clinical Trials in search of ongoing clinical studies focused on the COVID-19 vaccine. RESULTS: The patent search showed that most vaccines are based on viral vector platforms, nucleic acids, or protein subunits. The review also includes an overview of completed and ongoing clinical trials for SARS-CoV-2 in several countries. CONCLUSION: The information provided here lists vaccines for other types of coronavirus that have been used in the development of vaccines for COVID-19.

New nanotechnological formulation based on amiodarone-loaded lipid core nanocapsules displays anticryptococcal effect.

Cryptococcus neoformans is the etiological agent of cryptococcal meningoencephalitis. The recommended available treatment has low efficiency, with high toxicity and resistance as recurrent problems. In the search of new treatment protocols, the proposal of new pharmacological approaches is considered an innovative strategy, mainly nanotechnological systems considering fungal diseases. The antiarrhythmic drug amiodarone has demonstrated antifungal activity against a range of fungi, including C. neoformans. Here, considering the importance of calcium storage mediated by transporters on cryptococcal virulence, we evaluated the use of the calcium channel blocker amiodarone as an alternative therapy for cryptococcosis. C. neoformans displayed high sensitivity to amiodarone, which was also synergistic with fluconazole. Amiodarone treatment influenced some virulence factors, interrupting the calcium-calcineurin signaling pathway. Experiments with murine cryptococcosis models revealed that amiodarone treatment increased the fungal burden in the lungs, while its combination with fluconazole did not improve treatment compared to fluconazole alone. In addition, we have developed different innovative nanotechnological formulations, one of which combining two drugs with different mechanisms of action. Lipid-core nanocapsules (LNC) loaded with amiodarone (LNCAMD), fluconazole (LNCFLU) and both (LNCAMD+FLU) were produced to achieve a better efficacy in vivo. In an intranasal model of treatment, all the LNC formulations had an antifungal effect. In an intraperitoneal treatment, LNCAMD showed an enhanced anticryptococcal effect compared to the free drug, whereas LNCFLU or LNCAMD+FLU displayed no differences from the free drugs. In this way, nanotechnology using amiodarone formulations could be an effective therapy for cryptococcal infections.

Innovative hydrogel containing polymeric nanocapsules loaded with phloretin: Enhanced skin penetration and adhesion.

Dermatological applications of phloretin are restricted by its poor aqueous solubility. Nanotechnology has been proposed as strategy to increase the apparent drug solubility in aqueous media. This study aimed to develop, characterize, and evaluate the antitumoral effects and safety of polymeric nanocapsules containing phloretin (NCPhl). Further, to incorporate NC-Phl in an innovative semi-solid formulation (HG-NCPhl) to evaluate its performance using porcine skin model. NC-Phl was prepared and the effects in MRC5, HACAT, and SK-mel28 cells were evaluated. Hydrogels were prepared with Lecigel ® and characterized for their nanotechnological properties, adhesion (in vitro washability), and penetration/permeation studies in porcine skin. NC-Phl had a cytotoxic effect against Sk-Mel-28 cells and the population doubling time was increased upon treatment with NC-Phl for longer culture periods; notably when cells were treated for 72 h and then followed for 7 days after the treatment was removed (p < 0.05). HG-NC-Phl was considered adhesive and had a higher capacity to penetrate all skin layers compared with HG-Phl (p < 0.05). The innovative hydrogel HGNC-Phl promoted a drug-reservoir in the stratum corneum and higher penetration of the flavonoid into the epidermis. Therefore, this approach can be considered as a platform to establish versatile dermatological solutions for both cosmeceutics and melanoma therapy.

Technological Scenario for Masks in Patent Database During Covid-19 Pandemic.

Since January 2020, the World Health Organization announces COVID-19 outbreak a case of public health emergency of international interest, and declaring it a pandemic on March. Due to the high transmission of this disease, rate precautions have been implemented, such as the use of masks by the population, personal protective equipment (PPE), and safety protocols, mainly to health workers. Thus, we performed a patent review to evaluate the current patents related to the protective mask. The review was carried out in the patent database in the period of May 2019 to May 2020. After the process of screening and eligibility, 563 patents were selected for our analysis according to the aim of the study which used masks such as a PPE against dust particles and pathogens, mostly when it is about airborne transmission, such as viruses and bacteria. Here, an overview of the main materials used in the mask manufacturing and their efficiency was described. The results of the review showed that most of the masks used cotton, nylon, silver fiber fabrics, among others as fabrics to develop the masks. It also makes an analysis of masks composed of nanotechnology which provide high filtration efficiency. Moreover, the review also brought possibilities of masking the population, which already have been done in countries such as China and Korea and ways of sterilization for reuse of PPE during COVID-19 outbreak. Thus, this review can further researchers in the developing of masks to decrease the spread of a pandemic disease. Graphical abstract.

Altered aryl-hydrocarbon-receptor signalling affects regulatory and effector cell immunity in autoimmune hepatitis.

BACKGROUND & AIMS: In autoimmune hepatitis (AIH), the imbalance between regulatory T cells (Tregs) and T-helper type 17 (Th17) cells has been linked to low levels of CD39, an ectoenzyme that hydrolyses ATP, ultimately generating immunosuppressive adenosine. Upregulation of CD39 results from activation of aryl hydrocarbon receptor (AHR), which mediates toxin responses to modulate T-cell immunity. In this study, we investigated whether altered AHR signalling underlies defective CD39 expression and function in AIH Tregs and Th17 cells, therefore contributing to regulatory/effector cell imbalance. METHODS: Tregs and Th17 cells, obtained from the peripheral blood of 49 patients with AIH and 21 healthy individuals (HI), were tested for response to endogenous and exogenous AHR ligands. RESULTS: When compared to those of HI, AIH-derived Tregs and Th17 cells displayed impaired responses to AHR activation, reflected by impaired upregulation of CD39, delayed increase in ectoenzymatic activity, and defective Treg suppressive function. These impairments resulted, at least in part, from heightened levels of AHRR and Erα in Tregs and high HIF-1α in Th17 cells, and were reverted upon molecular blockade. Importantly, in AIH-derived Tregs, the binding affinity of AHR was higher for Erα than ARNT. CONCLUSIONS: In AIH, high levels of AHRR and HIF-1α inhibit AHR signalling in Tregs and Th17 cells. AHR non-canonical binding to Erα further amplifies the lack of effective CD39 upregulation. Blockade of these inhibitory and/or non-canonical activation pathways represents a potential therapeutic approach to restore CD39 and immunohomeostasis in AIH. LAY SUMMARY: In patients with autoimmune hepatitis, the imbalance between regulatory T cells and T helper type-17 cells is linked to dysfunction of the aryl hydrocarbon receptor pathway, resulting from aberrant inhibition or non-canonical activation. These alterations impair Treg- and Th17 cell-induced upregulation of CD39, an ectoenzyme key to immunoregulation. Blockade of excessive inhibition or non-canonical activation of the aryl hydrocarbon receptor pathway might represent a novel therapeutic strategy to control inflammation while restoring immune balance in autoimmune hepatitis.

Endogenous antisense RNA curbs CD39 expression in Crohn's disease.

CD39 is an ectonucleotidase that initiates conversion of extracellular nucleotides into immunosuppressive adenosine. CD39 is expressed by regulatory T (Treg)-cells, where it mediates immunosuppression, and by a subset of T-helper (Th) 17-cells, where it limits pathogenicity. CD39 is regulated via single-nucleotide-polymorphisms and upon activation of aryl-hydrocarbon-receptor and oxygen-mediated pathways. Here we report a mechanism of CD39 regulation that relies on the presence of an endogenous antisense RNA, transcribed from the 3'-end of the human CD39/ENTPD1 gene. CD39-specific antisense is increased in Treg and Th17-cells of Crohn's disease patients over controls. It largely localizes in the cell nucleus and regulates CD39 by interacting with nucleolin and heterogeneous-nuclear-ribonucleoprotein-A1. Antisense silencing results in CD39 upregulation in vitro and amelioration of disease activity in a trinitro-benzene-sulfonic-acid model of colitis in humanized NOD/scid/gamma mice. Inhibition/blockade of antisense might represent a therapeutic strategy to restore CD39 along with immunohomeostasis in Crohn's disease.

Dermatological applications of the flavonoid phloretin.

Botanical molecules are known to have the ability to counteract ultraviolet radiation-induced skin damage. The interest in the development of natural compound-based products for the prevention of solar ultraviolet radiation-induced skin photoaging, melasma, and photocarcinogenesis has been increasing. Recently, the flavonoid phloretin has attracted the attention of researchers in the dermatological field for application in cosmetics and therapeutics. In addition to its antioxidant activity, phloretin has been shown to have properties such as anti-aging and depigmenting effects. In this study, we review the dermatological treatments with phloretin for conditions such as melasma, photoaging, acne, and melanoma. Phloretin has been shown to inhibit elastase and matrix metalloproteinase-1 activity, to reduce cellular tyrosinase activity and melanin content, and induce apoptosis in B16 mouse melanoma 4A5 cells. An in vivo study showed that phloretin, applied topically to the dorsal skin of mice, suppressed the 12-O-tetradecanoylphorbol 13-acetate-induced expression of COX-2, a critical molecular target of many chemopreventive, as well as anti-inflammatory agents. Phloretin can penetrate the skin; nevertheless, its penetration profile in different skin layers has not yet been evaluated. Despite its health benefits, phloretin application has been limited because of its photoinstability and poor aqueous solubility, among other limitations. Therefore, we reviewed the recent advances in pharmaceutical applications such as the use of nanotechnology, in order to improve the cutaneous availability of phloretin. In this review, we also focus on the oral application, product development challenges, and recent progress and future research directions on phloretin.

Otoliths-composed gelatin/sodium alginate scaffolds for bone regeneration.

Evidence that otoliths, mineral-rich limestone concrescences present in the inner ear of bone fishes, can accelerate bone formation in vivo has been previously reported. The goal of this work was the development, characterization, and evaluation of the cytocompatibility of otoliths-incorporated sodium alginate and gelatin scaffolds. Cynoscion acoupa-derived otoliths were characterized by X-ray fluorescence spectrometry (FRX), particle size, free lime, and weight loss by calcination. Furthermore, otoliths were incorporated into sodium alginate (ALG/OTL-s) or gelatin (GEL/OTL-s) scaffolds, previously developed by freeze-drying. Then, the scaffolds were characterized by thermogravimetric analysis (TGA/DTG), differential scanning calorimetry (DSC), infrared spectroscopy with Fourier transform (FTIR), swelling tests, and scanning electron microscopy (SEM). Cytotoxicity assays were run against J774.G8 macrophages and MC3T3-E1 osteoblasts. Data obtained from TGA/DTG, DSC, and FTIR analyses confirmed the interaction between otoliths and the polymeric scaffolds. SEM showed the homogeneous porous 3D structure rich in otolith micro-fragments in both scaffolds. Swelling of the GEL/OTL-s (63.54 ± 3.0%) was greater than of ALG/OTL-s (13.36 ± 9.9%) (p < 0.001). The viability of J774.G8 macrophages treated with both scaffolds was statistically similar to the group treated with DMEM only (p > 0.05) and significantly higher than that treated with Triton-X (p < 0.01) at 72 h. Both scaffolds showed approximately 100% growth of MC3T3-E1 osteoblasts by 24 h, similarly to control (p > 0.05). However, by 48 h, only ALG/OTL-s showed growth similar to control (p > 0.05), whereas GEL/OTL showed a significantly lower growth index (p < 0.05). In conclusion, the physicochemical profiles suggest proper interaction between the otoliths and the two developed polymeric 3D scaffolds. Moreover, both materials showed cytocompatibility with J774.G8 macrophages but the growth of MC3T3-E1 osteoblasts was higher when exposed to ALG/OTL-s. These data suggest that sodium alginate/otoliths scaffolds are potential biomaterials to be used in bone regeneration applications. Graphical abstract.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Anti-HPV Nanoemulsified-Imiquimod: A New and Potent Formulation to Treat Cervical Cancer.

Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 µmol L-1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.