Photodynamic Therapy Directed to Melanoma Skin Cancer by Thermosensitive Hydrogel Containing Chlorophyll A.

Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC50 of 25.99 µM-an appealing result when compared to studies in the literature reporting an IC50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line.

Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.

Design and Characterization of Lipid-Surfactant-Based Systems for Enhancing Topical Anti-Inflammatory Activity of Ursolic Acid.

Skin inflammation is a symptom of many skin diseases, such as eczema, psoriasis, and dermatitis, which cause rashes, redness, heat, or blistering. The use of natural products with anti-inflammatory properties has gained importance in treating these symptoms. Ursolic acid (UA), a promising natural compound that is used to treat skin diseases, exhibits low aqueous solubility, resulting in poor absorption and low bioavailability. Designing topical formulations focuses on providing adequate delivery via application to the skin surface. The aim of this study was to formulate and characterize lipid-surfactant-based systems for the delivery of UA. Microemulsions and liquid crystalline systems (LCs) were characterized by polarized light microscopy (PLM), rheology techniques, and textural and bioadhesive assays. PLM supported the self-assembly of these systems and elucidated their formation. Rheologic examination revealed pseudoplastic and thixotropic behavior appropriate, and assays confirmed the ability of these formulations to adhere to the skin. In vivo studies were performed, and inflammation induced by croton oil was assessed for response to microemulsions and LCs. UA anti-inflammatory activities of ~60% and 50% were demonstrated by two microemulsions and 40% and 35% by two LCs, respectively. These data support the continued development of colloidal systems to deliver UA to ameliorate skin inflammation.

Functionalized lipid-based drug delivery nanosystems for the treatment of human infectious diseases.

Infectious diseases are still public health problems. Microorganisms such as fungi, bacteria, viruses, and parasites are the main causing agents related to these diseases. In this context, the search for new effective strategies in prevention and/or treatment is considered essential, since current drugs often have side effects or end up, causing microbial resistance, making it a serious health problem. As an alternative to these limitations, nanotechnology has been widely used. The use of lipid-based drug delivery nanosystems (DDNs) has some advantages, such as biocompatibility, low toxicity, controlled release, the ability to carry both hydrophilic and lipophilic drugs, in addition to be easel scalable. Besides, as an improvement, studies involving the conjugation of signalling molecules on the surfaces of these nanocarriers can allow the target of certain tissues or cells. Thus, this review summarizes the performance of functionalized lipid-based DDNs for the treatment of infectious diseases caused by viruses, including SARS-CoV-2, bacteria, fungi, and parasites.

Curcumin-Loaded Mesoporous Silica Nanoparticles Dispersed in Thermo-Responsive Hydrogel as Potential Alzheimer Disease Therapy.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. Curcumin-loaded mesoporous silica nanoparticles (MSN-CCM) can overcome the drawbacks related to the free curcumin (CCM) clinical application, such as water insolubility and low bioavailability, besides acting over the main causes associated to AD. A thermo-responsive hydrogel is an interesting approach for facilitating the administration of the nanosystem via a nasal route, as well as for overcoming mucociliary clearance mechanisms. In light of this, MSN-CCM were dispersed in the hydrogel and evaluated through in vitro and in vivo assays. The MSNs and MSN-CCM were successfully characterized by physicochemical analysis and a high value of the CCM encapsulation efficiency (EE%, 87.70 ± 0.05) was achieved. The designed thermo-responsive hydrogel (HG) was characterized by rheology, texture profile analysis, and ex vivo mucoadhesion, showing excellent mechanical and mucoadhesive properties. Ex vivo permeation studies of MSN-CCM and HG@MSN-CCM showed high permeation values (12.46 ± 1.08 and 28.40 ± 1.88 µg cm-2 of CCM, respectively) in porcine nasal mucosa. In vivo studies performed in a streptozotocin-induced AD model confirmed that HG@MSN-CCM reverted the cognitive deficit in mice, acting as a potential formulation in the treatment of AD.

Exploiting mesoporous silica, silver and gold nanoparticles for neurodegenerative diseases treatment.

Neurodegenerative diseases (NDs) are considered public health problem characterized by neural loss causing cognitive and behavioral impairments. It is currently possible to use drugs capable of controlling the symptoms caused by these diseases. However, treatment is not able to prevent neural loss. In addition, poor solubility, low bioavailability due to the inability for crossing the blood-brain barrier (BBB) are described as the main limitations of the treatment. Nanotechnology involves the development of nanoscale drug delivery systems and they have been employed to optimize therapeutics face to several diseases treatment. In light of this, this review describes the highlights on the fabrication of nanotechnology-based drug delivery systems emphasizing mesoporous silica, gold and silver nanoparticles (MSNs, AuNPs and AgNPs, respectively) and their biological behavior for the treatment of Alzheimer's and Parkinson diseases (ADs and PDs, respectively).

Solid lipid nanoparticles loaded with curcumin: development and in vitro toxicity against CT26 cells.

Aim: To develop a new curcumin carrier consisting of murumuru butter nanoparticles (SLN-Cs). Methods: A phase-inversion temperature method was used to produce SLN-Cs. The interaction of SLN-Cs with murine colon adenocarcinoma (CT26) cells in vitro was analyzed by confocal microscopy. Results: Stable SLN-Cs with a high curcumin-loading capacity were obtained. The SLN-Cs were more toxic to CT26 than free curcumin. Fluorescence microscopy images showed the SLN-Cs to be taken up by CT26 cells in vitro. Conclusion: These results indicate that SLN-Cs are suitable carriers of curcumin in aqueous media.

Mucoadhesive Nanosystems for Nose-to-Brain Drug Delivery in the Treatment of Central Nervous System Diseases.

The diseases affecting the Central Nervous System (CNS) can have varied etiopathology, but they have in common silent progression, global incidence, and significant impacts on the quality of life of patients and public health systems. With the advance of biomedicine and pharmaceutical technology, new and more modern diagnostic methods and treatments were developed, repurposing the use of drugs currently available for the treatment of CNS diseases. An attractive approach is the use of alternative drug delivery platforms, such as nanocarriers, and less invasive administration routes, such as the noseto- brain, extensively explored for the delivery of drugs into the CNS. Despite many promising results, the nose-to-brain route has some physiological limitations that make it difficult to deliver drugs satisfactorily to exert therapeutic activity in the CNS. To overcome these limitations, nanostructured systems with mucoadhesive properties have stood out over the last few years in pharmaceutical R&D. In this review; we discuss how the noseto- brain route limitations can influence the delivery of drugs to the CNS and highlight the benefits that mucoadhesion can bring to these nanostructured systems. The main findings in the literature are brought together and discussed critically, focusing on how mucoadhesion can improve the biopharmaceutical properties of molecules used in the clinic, as well as their biological performance. Finally, conclusions are drawn about the points of strength of mucoadhesive nanosystems and the points that still need attention to successfully use the nose-to-brain route for the treatment of diseases that affect the CNS.

Novel transdermal bioadhesive surfactant-based system for release and solubility improvement of antimalarial drugs artemether-lumefantrine.

Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods. Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy. A novel, surfactant-based ART-LUM formulation (S3AL), developed for transdermal delivery, may eliminate the shortcomings associated with oral delivery; namely poor drug absorption which is caused by the inherently low solubility of ART and LUM. Moreover, by successfully delivering these antimalarials transdermally, first-pass metabolism will be avoided leading to enhanced drug bioavailability in both cases. The S3AL formulation contained ART and LUM at equal concentrations (2.5% w/w of each) as well as Procetyl® AWS (30% w/w), oleic acid (10% w/w), 1-methyl-2-pyrrolidone (10% w/w), and water (45% w/w). The addition of LUM to the formulation changed the system from a striae structure to a dark field structure when visualized by a polarized light microscope. Additionally, this system possessed higher viscosity and superior skin bioadhesion, as evidenced by mechanical characterization, when compared to a similar formulation containing ART alone. S3AL was also proven to be biocompatible to human keratinocyte cells. Finally,in vitrostudies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 ± 295 µg cm-2of ART and 94 ± 13 µg cm-2of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria.

Polymeric-based drug delivery systems for veterinary use: State of the art.

One of the challenges to the success of veterinary pharmacotherapy is the limited number of drugs and dosage forms available exclusively to this market, due to the interspecies variability of animals, such as anatomy, physiology, pharmacokinetics, and pharmacodynamics. For this reason, studies in this area have become a highlight, since they are still scarce in comparison with those on human drug use. To overcome many limitations related to the bioavailability, efficacy, and safety of pharmacotherapy in animals, especially livestock and domestic animals, polymers-based drug delivery systems are promising tools if they guarantee greater selectivity and less toxicity in dosage forms. In addition, these tools may be developed according to the great interspecies variability. To contribute to these discussions, this paper provides an updated review of the major polymer-based drug delivery systems projected for veterinary use. Traditional and innovative drug delivery systems based on polymers are presented, with an emphasis on films, microparticles, micelles, nanogels, nanoparticles, tablets, implants and hydrogel-based drug delivery systems. We discuss important concepts for the veterinarian about the mechanisms of drug release and, for the pharmacist, the advantages in the development of pharmaceutical forms for the animal population. Finally, challenges and opportunities are presented in the field of pharmaceutical dosage forms for veterinary use in response to the interests of the pharmaceutical industry.

Highlights in poloxamer-based drug delivery systems as strategy at local application for vaginal infections.

Infectious diseases related to the vagina include diseases caused by the imbalance of the vaginal flora and by sexually transmitted infections. Some of these present themselves as a public health problem due to the lack of efficient treatment that leads to their complete cure, and others due to the growing resistance to drugs used in therapy. In this sense, new treatment strategies are desirable, with vaginal administration rout being a great choice since can bypass first-pass metabolism and decrease drug interactions and adverse effects. However, it is worth highlighting limitations related to patient's discomfort at application time. Thereby, the use of poloxamer-based drug delivery systems is desirable due its stimuli-sensitive characteristic. Therefore, the present review reports a brief overview of poloxamer properties, biological behavior and advances in poloxamer applications in controlled drug release systems for infectious diseases related to the vagina treatment and prevention.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization.

The indiscriminate use of antibiotics has facilitated the growing resistance of bacteria, and this has become a serious public health problem worldwide. Several microorganisms are still resistant to multiple antibiotics and are particularly dangerous in the hospital and nursing home environment, and to patients whose care requires devices, such as ventilators and intravenous catheters. A list of twelve pathogenic genera, which especially included bacteria that were not affected by different antibiotics, was released by the World Health Organization (WHO) in 2017, and the research and development of new antibiotics against these genera has been considered a priority. The nanotechnology is a tool that offers an effective platform for altering the physicalchemical properties of different materials, thereby enabling the development of several biomedical applications. Owing to their large surface area and high reactivity, metallic particles on the nanometric scale have remarkable physical, chemical, and biological properties. Nanoparticles with sizes between 1 and 100 nm have several applications, mainly as new antimicrobial agents for the control of microorganisms. In the present review, more than 200 reports of various metallic nanoparticles, especially those containing copper, gold, platinum, silver, titanium, and zinc were analyzed with regard to their anti-bacterial activity. However, of these 200 studies, only 42 reported about trials conducted against the resistant bacteria considered a priority by the WHO. All studies are in the initial stage, and none are in the clinical phase of research.

The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems.

Neurological disorders have been growing in recent years and are highly prevalent globally. Resveratrol (RES) is a natural product from plant sources such as grape skins. This compound has shown biological activity in many diseases, in particular, those that act on the central nervous system. The mechanism of action and the key points in neurological disorders were described and show the targeted mechanism of action. Due to the insolubility of this compound; the use of nanotechnology-based systems has been proposed for the incorporation of RES and RES-loaded nanocarriers have been designed for intranasal administration, oral or parenteral routes to deliver it to the brain. In general, these nanosystems have shown to be effective in many studies, pharmacological and pharmacokinetic assays, as well as some cell studies. The outcomes show that RES has been reported in human clinical trials for some neurological diseases, although no studies were performed in humans using nanocarriers, animal and/or cellular models have been reported to show good results regarding therapeutics on neurological diseases. Thus, the use of this nutraceutical has shown true for neurological diseases and its loading into nanocarriers displaying good results on the stability, delivery and targeting to the brain.

Nanosystems against candidiasis: a review of studies performed over the last two decades.

The crescent number of cases of candidiasis and the increase in the number of infections developed by non-albicans species and by multi-resistant strains has taken the attention of the scientific community, which has been searching for new therapeutic alternatives. Among the alternatives found the use of nanosystems for delivery of drugs already commercialized and new biomolecules have grown, in order to increase stability, solubility, optimize efficiency and reduce adverse effects. In view of the growing number of studies involving technological alternatives for the treatment of candidiasis, the present review came with the intention of gathering studies from the last two decades that used nanotechnology for the treatment of candidiasis, as well as analysing them critically and pointing out the future perspectives for their application with this purpose. Different studies were considered for the development of this review, addressing nanosystems such as metallic nanoparticles, mesoporous silica nanoparticles, polymeric nanoparticles, liposomes, nanoemulsion, microemulsion, solid lipid nanoparticle, nanostructured lipid carrier, lipidic nanocapsules and liquid crystals; and different clinical presentations of candidiasis. As a general overview, nanotechnology has proven to be an important ally for the treatment against the diversity of candidiasis found in the clinic, whether in increasing the effectiveness of commercialized drugs and reducing their adverse effects, as well as allowing exploring more effectively properties therapeutics of new biomolecules.

A Review of Analytical Methods for the Determination of Hypericin in Foods, Herbal, Biological and Pharmaceutical Matrices.

AIMS: A review of analytical methods for the determination of hypericin in foods, herbal, biological and pharmaceutical matrices. BACKGROUND: Hypericin (HYP) is a naturally-occurring pigment obtained from some plants of the genus Hypericum. Although HYP has been known for many years, it has recently attracted attention due to its varied biological properties, such as anti-inflammatory and antidepressant activity and it is also an efficient photosensitizer. OBJECTIVE: The objective of this review is to provide insights into the physicochemical properties of HYP, as well as to report the analytical methods existing in the literature and official compendia for different matrices. METHODS: The survey data were collected by Google Scholar® and Scopus® using keys terms. RESULT: Analytical methods involving HYP are mainly concerned with the quality control of pharmaceutical preparations, foods, beverages, biological samples and drug delivery systems using different types of analysis methods. Some difficulties have also been identified due to the physicochemical properties of HYP. It presents great solubility in alkaline solutions, organic bases and common polar organic solvents. CONCLUSION: It can be analyzed by thin layer chromatography, spectrophotometry in the ultraviolet region, but the most commonly used method is by HPLC. HYP presents monographs in the American, British and European Pharmacopoeias, however, the methods of analysis are not yet harmonized.

Synthesis and Characterization of Nanostructured Lipid Nanocarriers for Enhanced Sun Protection Factor of Octyl p-methoxycinnamate.

Sunlight is important to health, but higher exposure to radiation causes early aging of the skin and skin damage that can lead to skin cancers. This study aimed at producing a stable octyl p-methoxycinnamate (OMC)-loaded nanostructured lipid carrier (NLC) sunscreen, which can help in the photoprotective effect. NLC was produced by emulsification-sonication method and these systems were composed of myristyl myristate (MM), caprylic capric triglyceride (CCT), Tween® 80 (TW), and soybean phosphatidylcholine (SP) and characterized by dynamic light scattering (DLS), zeta potential (ZP) measurement, atomic force microscopy (AFM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and in vitro release studies. Pre-formulation studies were performed changing TW concentrations and no differences were found at concentrations of 1.0 and 2.0%. Two selected formulations were designed and showed an average size of 91.5-131.7, polydispersity index > 0.2, and a negative value of ZP. AFM presented a sphere-like morphology and SEM showed ability to form a thin film. DSC exhibited that the incorporation of OMC promoted reduction of enthalpy due to formation of a more amorphous structure. Drug release shows up to 55.74% and 30.57%, and this difference could be related to the presence of SP in this formulation that promoted a more amorphous structure; the release mechanism study indicated Fickian diffusion and relaxation. Sun protection factor (SPF) evaluation was performed using NLC and presented values around 40, considerably higher than those observed in the literature. The developed formulations provide a beneficial alternative to conventional sunscreen formulations.

Advances and challenges in nanocarriers and nanomedicines for veterinary application.

To ensure success in the development and manufacturing of nanomedicines requires forces of an interdisciplinary team that combines medicine, engineering, chemistry, biology, material and pharmaceutical areas. Numerous researches in nanotechnology applied to human health are available in the literature. Althought, the lack of nanotechnology-based pharmaceuticals products for use exclusively in veterinary pharmacotherapy creates a potential area for the development of innovative products, as these animal health studies are still scarce when compared to studies in human pharmacotherapy. Nano-dosage forms can ensure safer and more effective pharmacotherapy for animals and can more be safer for the consumers of livestock products, once they can offer higher selectivity and smaller toxicity associated with lower doses of the drugs. In addition, the development and production of nanomedicines may consolidate the presence of pharmaceutical laboratories in the global market and can generate greater profit in a competitive business environment. To contribute to this scenario, this article provides a review of the main nanocarriers used in nanomedicines for veterinary use, with emphasis on liposomes, nanoemulsions, micelles, lipid nanoparticles, polymeric nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and dendrimers, and the state of the art of application of these nanocarriers in drug delivery systems to animal use. Finnaly, the major challenges involved in research, scale-up studies, large-scale manufacture, analytical methods for quality assessment, and regulatory aspects of nanomedicines were discussed.

Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration.

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

Characteristics, Biological Properties and Analytical Methods of Trans-Resveratrol: A Review.

Trans-resveratrol (TR) is the biological active isomer of resveratrol and the one responsible for therapeutic effects; both molecules are non-flavonoid phenolics of the stilbenes class found mainly in berries and red grapes. TR biological properties lie in modulation of various enzymatic classes. It is a promising candidate to novel drugs due its applications in pharmaceutical and cosmetic industries, such as anticarcinogenic, antidiabetic, antiacne, antioxidant, anti-inflammatory, neuroprotective, and photoprotector agent. It has effects on bone metabolism, gastrointestinal tract, eyes, kidneys, and in obesity treatment as well. Nevertheless, its low solubility in water and other polar solvents may be a hindrance to its therapeutic effects. Various strategies been developed to overcome these issues, such as the drug delivery systems. The present study performed a research about methods to identify TR and RESV in several samples (raw materials, wines, food supplements, drug delivery systems, and blood plasma). Most of the studies tend to analyze TR and RESV by high performance liquid chromatography (HPLC) coupled with different detectors, even so, there are reports of the use of capillary electrophoresis, electron spin resonance, gas chromatography, near-infrared luminescence, UV-Vis spectrophotometer, and vibrational spectrophotometry, for this purpose. Thus, the review evaluates the biological activity of TR and demonstrates the currently used analytical methods for its quantification in different matrices.