Search Results (1,830)

The objective of this review is to provide an in-depth overview of the current state of research on microneedles for drug delivery, with emphasis on composite systems, particularly those based on hyaluronic acid (HA) and zinc oxide as composite systems. The review discusses the advantages, challenges, and future directions associated with the use of these materials for microneedle-based drug delivery. Hyaluronic acid, which is naturally found in human tissue, has been shown to enhance drug permeation and improve skin hydration, while ZnO has provided high mechanical durability and prevented microbial and bacterial growth. The use of dissolvable microneedles is a viable substitute for traditional drug delivery methods such as oral or intravenous administration. Ongoing research is being conducted to further improve the performance, safety, and effectiveness of microneedles for various drug delivery applications. Full article

Antiretroviral drugs are associated with increased body weight and metabolic disorders. Fat gain and insulin resistance are commonly associated with abdominal obesity in people with HIV (PWH). There is currently an open ongoing discussion about how antiretroviral therapy affects body weight and its significance in hunger–satiety circuit alteration. Until now, the impact of the drug on this circuit has not been explored. This study aimed to assess the hormones involved in appetite and satiety regulation in the serum and hypothalamus after efavirenz (EFV) administration in mice. EFV (10 mg/kg) and distilled water (1.5 μL/kg) (control group) were orally administered for 36 days to CD1 mice. Body weight and food intake were determined throughout treatment. At the end of the treatment, the metabolic profile (glucose, triglycerides, cholesterol) was assessed, and leptin, soluble receptor of leptin (sOB-R), and ghrelin were measured in serum; moreover, we evaluated the expression of growth hormone secretagogue receptor 1a (GHS-R1a), neuropeptide Y receptor 1 (NPYR1), and leptin in the hypothalamus, and a sucrose preference test (SPT) was conducted. Outcomes showed an increase in serum ghrelin and the expression of GHS-R1a and NPYR1 receptors in the hypothalamus, coinciding with an increase in appetite and preference for sucrose in mice in the EFV group. Furthermore, serum leptin, sOB-R, and the free leptin index (FLI) showed that hunger is not related to a lack of satiety. Despite increased food intake, a reduction in body weight was observed, and triglyceride and cholesterol levels were increased. According to our findings, mice treated with EFV showed a decrease in body weight, despite increased food intake resulting from appetite stimulation, which is caused by specific compounds, hormones, and neural signals acting on the brain’s hunger centres, primarily in the hypothalamus, promoting eating behaviours. However, further studies are necessary to investigate the mechanisms of EFV’s effects on energy expenditure. Full article

Background/Objectives: Combination therapy for schizophrenia may exacerbate side effects mediated by multiple brain receptors. This study aimed to elucidate the pharmacodynamic and pharmacokinetic interactions between chlorpromazine and risperidone. We investigated dopamine 2 (D₂), serotonin 2A (5-HT_2A), histamine 1 (H₁), and muscarinic acetylcholine (mACh) receptor occupancy in the brain as well as pharmacokinetic interactions after oral administration of chlorpromazine and risperidone in rats. Methods: Rats were orally administered chlorpromazine, risperidone, or their combination. A tracer cocktail solution was injected intravenously to measure multiple receptor occupancies simultaneously. Tracer and drug concentrations in the brain tissue and plasma were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Receptor occupancy increased in a dose-dependent manner. The doses required for 70% D₂ receptor occupancy were 4.5 mg/kg for chlorpromazine and 1.5 mg/kg for risperidone. Co-administration of chlorpromazine (4.5 mg/kg) and risperidone (1.5 mg/kg) resulted in an increase in D₂ and 5-HT_2A receptor occupancy to approximately 90%. Risperidone alone caused a transient increase in H₁ receptor occupancy to 80%, while co-administration increased mACh receptor occupancy to 60%. Co-administration with chlorpromazine significantly increased the plasma concentrations of risperidone and its metabolite, paliperidone, and decreased the oral clearance of risperidone by 5.9-fold. Conclusions: Co-administration of chlorpromazine and risperidone increases the occupancy of D₂, 5-HT_2A, and mACh receptors in the rat brain and increases the plasma concentrations of risperidone and paliperidone, suggesting a potential risk of enhanced adverse effects due to both pharmacokinetic and pharmacodynamic interactions involving target and non-target brain receptors. Full article

Valsartan (Val)—a lipophilic non-peptide angiotensin II type 1 receptor antagonist—is highly effective against hypertension and displaying limited solubility in water (3.08 μg/mL), thereby resulting in low oral bioavailability (23%). The limited water solubility of antihypertensive drugs can pose a challenge, particularly for rapid and precise administration. Herein, we synthesize and characterize valsartan-containing silver nanoparticles (Val-AgNPs) using Mangifera indica leaf extracts. The physicochemical, structural, thermal, and pharmacological properties of these nano-conjugates were established through various analytical and structural tools. The spectral shifts in both UV-visible and FTIR analyses indicate a successful interaction between the valsartan molecule and the silver nanoparticles. The resulting nano-conjugates are spherical and within the size range of 30–60 nm as revealed in scanning electron-EDS and atomic force micrographs. The log-normal distribution of valsartan-loaded nanoparticles, with a size range of 30 to 60 nm and a mode of 54 nm, indicates a narrow, monodisperse, and highly uniform particle size distribution. This is a favorable characteristic for drug delivery systems, as it leads to enhanced bioavailability and a consistent performance. Dynamic Light Scattering (DLS) analysis of the Val-AgNPs indicates a polydisperse sample with a tendency toward aggregation, resulting in larger effective sizes in the suspension compared to individual nanoparticles. The accompanying decrease in zeta potential (to −19.5 mV) and conductivity further supports the idea that the surface chemistry and stability of the nanoparticles changed after conjugation. Differential scanning calorimetry (DSC) demonstrated the melting onset of the valsartan component at 113.99 °C. The size-dependent densification of the silver nanoparticles at 286.24 °C correspond to a size range of 40–60 nm, showing a significant melting point depression compared to bulk silver due to nanoscale effects. The shift in Rf for pure valsartan to Val-AgNPs suggests that the interaction with the AgNPs alters the compound’s overall polarity and/or its interaction with the stationary phase, complimented in HPTLC and HPLC analysis. The stability and offloading behavior of Val-AgNPs was observed at pH 6–10 and in 40% and 80% MeOH. In addition, Val-AgNPs did not reveal hemolysis or significant alterations in blood cell indices, confirming the safety of the nano-conjugates for biological application. In conclusion, these findings provide a comprehensive characterization of Val-AgNPs, highlighting their potential for improved drug delivery applications. Full article

Dry eye disease is a common condition in which tear production or quality is insufficient to lubricate the eyes properly. Standard treatment usually involves lubricating eye drops. In this study, we assessed the human health risks, including both non-carcinogenic and carcinogenic effects, associated with long-term exposure to the chemical elements arsenic (As), cadmium (Cd), cobalt (Co), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn) in eye drops used in Brazil. The results indicated that the Co concentration (1.1048 mg/kg) in the eye drops sample 5 exceeded the limit established by the ICH Q3D (R2) guideline for parenteral products (0.5000 mg/kg). Additionally, As levels in eye drop samples 2, 8–10, 12, 13, and 16, as well as Cd levels in samples 2, 3, 8–10, and 12, exceeded the limits established by the Brazilian Pharmacopoeia for parenteral administration (0.0500–0.0532 mg/kg). The main health risk appears to come from oral exposure, as the drug can drain into the nasal cavity via the nasolacrimal duct and then be absorbed through the gastrointestinal tract. While none of the tested eye drops posed non-carcinogenic risks, carcinogenic risks from oral exposure to As and Cd were identified, with overall risk levels exceeding acceptable thresholds. These findings emphasize the need for strict regulation and continuous monitoring of these products to reduce health risks and prevent long-term damage. Full article

Huntington’s Disease (HD) is characterized by prominent degeneration of the principal neurons of the striatum and by progressive motor and cognitive deterioration. Striatal neurons degenerate in HD due to multiple cell-autonomous and non-autonomous factors. Impaired neurotrophin signaling by brain-derived neurotrophic factor (BDNF) and its cognate receptor Tropomyosin receptor kinase B (TrkB) is an important mechanism underlying neuronal loss in HD. Fingolimod, a clinically approved oral drug for Multiple Sclerosis, was originally developed based on its anti-inflammatory properties. Recent work suggests that fingolimod can also promote BDNF expression and enhance neurotrophic support in the brain. We hypothesized that fingolimod treatment initiated during the presymptomatic phase would increase striatal BDNF levels and protect against motor dysfunction in HD. In wild-type mice, fingolimod treatment increases striatal BDNF levels and enhances BDNF-TrkB signaling. However, chronic fingolimod therapy (0.1 mg/kg, i.p., twice per week, over 7 weeks) initiated at age 4 weeks in the R6/2 mouse model of HD failed to improve behavioral locomotor deficits and exacerbated limb clasping. Furthermore, fingolimod treatment in these presymptomatic R6/2 mice acutely decreased BDNF-TrkB signaling in the striatum in a dose-dependent manner. In contrast, acute administration of fingolimod in symptomatic 7-week-old R6/2 mice increased striatal BDNF-TrkB signaling in a dose-dependent manner, consistent with previous work suggesting that chronic fingolimod can improve motor behavior when given during the symptomatic phase. Thus, the effects of fingolimod striatal BDNF-TrkB signaling and motor behavior in HD are complex and vary with disease stage. Addressing this variability is critical for the design of neuroprotective drug trials in HD, including those utilizing sphingosine-1-phosphate receptor (S1P) modulators. Full article

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 3² factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine. Full article

Arabinoxylans (AX) are polysaccharides capable of forming covalent gels stable under variations in pH and temperature. They are fermentable by the colonic microbiota, making them appropriate carriers for colon-targeted oral drug delivery, including insulin. This study aimed to fabricate covalent AX nanoparticles loaded with insulin (NPAXI) using a 0.25 (AX/insulin) mass ratio and to evaluate their colon-targeted capacity to improve glycemic control in diabetic rats. In parallel, we assessed gut microbiota modulation as a secondary outcome, derived from the prebiotic fermentation of AX, considered an additional benefit. NPAXI, produced by coaxial electro spraying, displayed a mean diameter of 661 nm, a zeta potential of −31 mV, and high insulin encapsulation efficiency. Bioassay demonstrated that a single oral NPAXI dose restored normoglycemia for 9 h, starting 15 h post-administration. Gut microbiota analysis revealed that while insulin alone increased Lactobacillaceae, it failed to suppress Enterobacteriaceae. NPAXI treatment, however, promoted beneficial taxa such as Muribaculaceae and Prevotellaceae and reduced proinflammatory families like Desulfovibrionaceae and Helicobacteraceae. These microbial shifts paralleled the improved glycemic profile, suggesting a synergistic interaction between AX and insulin in reestablishing gut microbial homeostasis and metabolic regulation. Overall, NPAXI represents a promising strategy for colon-targeted oral insulin delivery, offering additional microbiota-modulating benefits. Full article

Background/Objectives: Given the clinical limitations of azathioprine (AZA) in treating inflammatory bowel disease, this study developed an AZA-loaded microbiota-modulating and colon-targeted nanoparticle constructed from pectin, Zein, and Eudragit^®S100 (APZE), which was hypothesized to enhance efficacy while reducing toxicity. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to simultaneously quantify AZA and its metabolites, enabling the investigation of the pharmacokinetic and microbial metabolism differences between APZE and AZA suspension (AZAS). Methods: APZE was characterized, and an LC-MS/MS method was developed for quantifying AZA and its metabolites in multiple matrices. Given the potential of APZE for colon targeting and modulation of the microbiota, which may affect drug absorption, distribution, and microbiota-mediated metabolism, we determined analyte concentrations in rat plasma, tissues, and microbial cultures at different time points following administration of APZE or AZAS. Results: AZA, 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanine (6-TG) were quantified in positive ion mode, and 6-thiouric acid (6-TU) in negative ion mode. The assay demonstrated excellent accuracy, precision, and stability over the concentration range of 5–1000 ng/mL. Orally administered APZE exhibited higher bioavailability, improved intestinal absorption, and reduced formation of the inactive metabolite 6-TU compared to AZAS. In microbial cultures, AZA was metabolized primarily to 6-MP, and APZE underwent more extensive metabolism to 6-MP than AZAS. Conclusions: This method provides accurate and precise quantification of physiologically relevant concentrations of AZA and its metabolites (6-MP, 6-MMP, 6-TG, and 6-TU), offering a bioanalytical tool for the pharmacokinetic and gut microbiota metabolism studies of AZA formulations. These findings suggest that APZE is a promising drug delivery formulation. Full article

Currently, there are various approaches to the treatment of diabetes. Regarding type 2 diabetes (T2D), treatment focuses on blood glucose control. When changes in lifestyle do not achieve this glycemic control, the option is to start therapy with antidiabetic drugs such as metformin. However, long-term metformin use causes disturbances that may affect treatment approaches. This review examines recent advances in nanotechnology that have developed new forms of drug administration that can improve the efficacy of the treatment, where nanomaterials, nanostructures, and nanoparticle design are involved, so that they provide controlled and gradual release. The use of biopolymers (as drug delivery systems) has ensured biocompatibility, biodegradability, and low toxicity. There are several methods for obtaining a drug delivery system, including electrospinning, electrospraying, nanoprecipitation, etc. These systems improve drug delivery and can be used orally, transdermally, or intravenously, among means of administration. This review describes the new forms of the administration of metformin in the treatment of T2D, based on the encapsulation of metformin in polymeric matrices such as proteins, polysaccharides, and lipids, among others. Full article

Background: Pediatric patients often receive medicines manipulated from adult formulations due to a lack of age-appropriate products. While such practices are clinically routine, they may reflect deeper systemic deficiencies in pediatric pharmacotherapy. Objective: This scoping review aimed to map the prevalence, definitions, and types of pediatric drug manipulation and to conceptualize manipulation as an indicator of structural gaps in formulation science, regulation, and access. Methods: A systematic search of PubMed (January 2014–July 2024) included 10 studies reporting the frequency of drug manipulation in children aged ≤18 years. Eligible studies were synthesized narratively according to PRISMA-ScR guidelines. Results: Ten studies from nine countries were included, reporting manipulation frequencies ranging from 6.4% to 62% of all drug administrations and up to 60% at the patient level. Manipulated formulations most commonly included oral solid doses, altered through dispersing, splitting, or crushing. Definitions and methodologies varied considerably. The findings revealed five recurring structural gaps: limited pediatric formulations, inconsistent regulatory implementation, lack of standardized definitions and guidance, insufficient evidence on manipulation safety, and inequitable access across regions. Conclusion: Manipulation of finished dosage forms for use in children is a widespread, measurable phenomenon reflecting systemic inadequacies in formulation development, regulation, and access. Recognizing manipulation as a structural indicator may guide policy, innovation, and equitable pediatric pharmacotherapy worldwide. Full article

The incorporation of drugs into nanostructured silica has proven to be an effective strategy for delaying drug release, protecting against enzymatic degradation, and enhancing therapeutic efficacy. Specifically, crotoxin, a component derived from the venom of Crotalus durissus terrificus, exhibits notable analgesic and immunomodulatory properties. Previous studies have demonstrated that encapsulating crotoxin within SBA-15 nanostructured mesoporous silica not only reduces its toxicity and enhances its analgesic effects but also enables effective oral administration. Given its promising efficacy and the expanding interest in its application across various experimental models and potential therapeutic uses, this study aimed to conduct a detailed analysis of the physicochemical properties of crotoxin when incorporated into SBA-15 silica. Following characterization, the crotoxin–SBA-15 complex was orally administered to mice in an experimental model of ulcerative colitis (UC). The most widely adopted experimental model for studying UC involves the administration of dextran sodium sulfate (DSS) in drinking water to induce colonic inflammation in susceptible animals. In this study, we hypothesized that crotoxin incorporated into ordered mesoporous silica (SBA-15) could modulate DSS-induced UC. Crotoxin was successfully incorporated into SBA-15 and administered orally, as its physicochemical properties supported this route of delivery. Mice received the crotoxin–SBA-15 complex either at the onset of UC induction or on days 1 and 4 after DSS exposure. Seven days after the start of DSS administration, we observed a substantial reduction (approximately 50%) in Disease Activity Index (DAI) scores, accompanied by marked improvements in the histopathological features of the colon. These findings indicate for the first time that crotoxin incorporated into SBA-15 exhibits significant therapeutic potential in the treatment of experimentally induced ulcerative colitis. Full article

Plants have been used for medicinal purposes both intuitively and based on traditional knowledge for centuries. Recently, however, there has been a significant increase in research focused on medicinal plants to meet the growing demands of the pharmaceutical industry. As a result, it has become essential to evaluate the safety of natural products for human use. This review examines in vitro and in vivo toxicity studies of lectins, a class of plant proteins with pharmacological applications. The reviewed data indicate that many of these proteins do not appear to be toxic to human and animal cells, nor when administered to rodents through oral, intraperitoneal, or intravenous routes. However, some lectins have shown toxicity under certain conditions, such as depending on the administration route, dose, and treatment duration. These adverse effects may include behavioral changes, antinutritional effects, hepatotoxicity, nephrotoxicity, pancreatic hypertrophy, allergic reactions, and even death. Therefore, it is crucial to prioritize toxicological studies to ensure the safety of these plant proteins as potential drug candidates in the future. Full article

Disorders in the oral cavity caused by pathogenic fungi pose a significant clinical challenge, particularly in immunocompromised patients, as well as those undergoing oncological therapy or antibiotic treatment. A practical therapeutic approach involves the topical application of mucoadhesive drug dosage forms. However, only a limited number of such preparations are available on the pharmaceutical market. Mucoadhesive systems are especially advantageous, as they ensure prolonged retention and adequate concentrations of the active substances at the site of infection. Localized drug delivery enhances therapeutic efficacy compared to systemic administration, enabling lower drug doses, and consequently reducing the risk of side effects. Moreover, many fungal conditions require long-term treatment, which may be optimized by the use of mucoadhesive systems, improving patient compliance. Considering the issue of limited adhesion of conventional drug dosage forms and the moist environment in the oral cavity, providing optimal mucoadhesive properties is a key aspect. This article presents a comprehensive overview of the significance of treating oral candidiasis using mucoadhesive drug dosage forms, the mechanisms and advantages of mucoadhesion (including relevant polymers), and, most importantly, recent scientific reports on the development and quality assessment of mucoadhesive drug delivery systems for the management of oral fungal diseases. Full article

Brachyspira hyodysenteriae is the primary cause of swine dysentery, characterized by bloody to mucoid diarrhea due to mucohaemorhagic colitis in pigs. The disease primarily affects pigs during the growth and finishing stage. The control and prevention of B. hyodysenteriae consists of the administration of antimicrobial drugs, in addition to management and adapted feeding strategies. A worldwide re-emergence of the disease has recently been reported with an increasing number of isolates demonstrating decreased susceptibility to several crucially important antimicrobials in the control of swine dysentery. This compromises the possibilities to eradicate B. hyodysenteriae from infected pig farms. A novel non-antibiotic zinc chelate has been reported to demonstrate positive effects on fecal quality and consistency, general clinical signs, average daily weight gain, and B. hyodysenteriae excretion during and after a 6-day oral treatment. The objective of the present study was to evaluate the zinc chelate (IntraDysovinol^® 499 mg/mL; IntraCare) within an eradication schedule with naturally occurring swine dysentery due to B. hyodysenteriae resistant to pleuromutilins under field conditions in Belgium. We evaluated a 14-day treatment schedule combined with alternative management measures (including partial depopulation of post-weaning facilities and improved external and internal biosecurity measures) and thorough cleaning and disinfection (including 2% NaOH) of the buildings and the sows from day 7 of treatment onwards. This alternative approach for B. hyodysenteriae eradication was evaluated on 18 pig farms over a 5-year period. All enrolled eradication programs were evaluated as successful at least 6–9 months after the finalization of the protocol. In conclusion, the zinc chelate product has an excellent potential for application within an eradication protocol of B. hyodysenteriae that are diagnosed as resistant to pleuromutilins. The combined approach of zinc chelate treatment and alternative management measures is demonstrated to be successful in the eradication of farrow-to-wean, farrow-to-finish, and finishing pig farms under field conditions in Belgium. Full article