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Scientific Reports Dec 2023The Patient Preference Survey aims to understand unmet needs related to riluzole management in people with Amyotrophic Lateral Sclerosis (ALS) and to identify which...
The Patient Preference Survey aims to understand unmet needs related to riluzole management in people with Amyotrophic Lateral Sclerosis (ALS) and to identify which characteristics of a new formulation could better match their preferences. The survey involved 117 people with ALS (PALS) treated with riluzole in four European countries. The dysphagic PALS were least satisfied with the riluzole tablet and oral suspension and with ease in self-administration; up to 68% of respondents postponed or missed the treatment due to swallowing difficulties and need of caregiver assistance. Overall, 51% of tablet and 53% of oral suspension users regularly crushed or mixed riluzole with beverages, respectively; PALS who always manipulated riluzole showed low satisfaction with the formulation and considered the risk of choking and pneumonia the most worrisome event. The survey evaluated the driving factors in choosing/switching the therapy: 67% of PALS declared a low risk of choking. The research finally evaluated which attributes of a new formulation would be preferred: the most relevant were ease of use (4.3/5), convenient/portable packaging (4.0/5) and oral-dissolving properties without tongue motility (3.9/5). The Patient Preference Survey suggests that patients have several unmet needs and preferences that could be addressed by a different formulation, e.g. using oral film technologies.
Topics: Humans; Riluzole; Amyotrophic Lateral Sclerosis; Suspensions; Europe; Airway Obstruction; Tablets; Neuroprotective Agents
PubMed: 38110502
DOI: 10.1038/s41598-023-49424-3 -
Drugs in R&D Sep 2023The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism.
OBJECTIVE
The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin.
METHODS
In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters.
RESULTS
The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (C: 2332 ± 950 pg/mL; T: 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (C: 1151 ± 565 pg/mL; T: 64.2 ± 44.2 min; p < 0.001 for comparison of C and T) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated.
CONCLUSIONS
The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form.
TRIAL REGISTRY
Registration number: NCT04574141.
Topics: Humans; Male; Biological Availability; Cross-Over Studies; Melatonin; Tablets; Volunteers; Administration, Oral; Area Under Curve
PubMed: 37438493
DOI: 10.1007/s40268-023-00431-9 -
International Journal of Nanomedicine 2023The aim of this study was to develop a liposome gel containing -tetrahydropalmatine (-THP) and evaluate its transdermal properties.
PURPOSE
The aim of this study was to develop a liposome gel containing -tetrahydropalmatine (-THP) and evaluate its transdermal properties.
METHODS
A L (4) orthogonal experiment was conducted to optimize the preparation of -THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M membrane, respectively. The metabolism of -THP in liver and skin S9 fractions was also studied.
RESULTS
The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and -THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of -41.27 mV. Both the -THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (C) of -THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (t) was 1.2 hours. The relative bioavailability of -THP in the liposome gel was 233.8% compared to the emulsion. The concentration of -THP (prepared in PBS) decreased at a rate of 0.0067 μg/mL/min in the liver S9 fraction and 0.0027 μg/mL/min in the skin S9 fraction, however, this difference was not observed when -THP was encapsulated in liposomes. -THP passed through the Strat-M membrane at a rate of 0.0032 mg/cm/h and 0.002 mg/cm/h for the emulsion and liposome gel, respectively.
CONCLUSION
The optimal process for the preparation of -THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for -THP during storage.
Topics: Animals; Rats; Liposomes; Emulsions; Skin; Lecithins
PubMed: 37600118
DOI: 10.2147/IJN.S422305 -
Cancer Treatment and Research... 2024One of the cancers that affect men, prostate cancer considerably raises mortality rates for males around the world. Patients with prostate cancer can have a localized or... (Review)
Review
One of the cancers that affect men, prostate cancer considerably raises mortality rates for males around the world. Patients with prostate cancer can have a localized or advanced form of the illness. Digital rectal examinations, prostate-specific antigen analyses, and prostate biopsies are all used to identify prostate cancer. The onset, development, and spread of cancer are all correlated with mutations in specific genes. Radical prostatectomy, ablative radiation, and active surveillance are all forms of treatment for localized prostate cancer. Androgen deprivation therapy (ADT), radiation, and chemotherapy are given to men who have metastatic prostate cancer or have experienced a relapse. When compared to traditional cancer chemotherapeutic methods, the liposome-based drug delivery technology offers less toxic, biodegradable, and biocompatible nanomedicine. Liposomes offer great advantages for use in nanomedicines by improving the sensitivity, specificity, and persistence of these anti-malignant cell agents in the body. Liposomal formulations are undergoing clinical trials of variety of cancers including prostate cancer. The present narrative review describes the composition and types of liposomes, its advantages, disadvantages, and the methods of preparation, research studies, clinical applications, drug repurposing and administration.
Topics: Humans; Liposomes; Male; Prostatic Neoplasms; Antineoplastic Agents; Drug Delivery Systems; Nanomedicine
PubMed: 38367412
DOI: 10.1016/j.ctarc.2024.100792 -
BioMed Research International 2023Numerous disorders go untreated owing to a lack of a suitable drug delivery technology or an appropriate therapeutic moiety, particularly when toxicities and side... (Review)
Review
Numerous disorders go untreated owing to a lack of a suitable drug delivery technology or an appropriate therapeutic moiety, particularly when toxicities and side effects are a major concern. Treatment options for microbiological infections are not fulfilled owing to significant adverse effects or extended therapeutic options. Advanced therapy options, such as active targeting, may be preferable to traditional ways of treating infectious diseases. Niosomes can be defined as microscopic lamellar molecules formed by a mixture of cholesterol, nonionic surfactants (alkyl or dialkyl polyglycerol ethers), and sometimes charge-inducing agents. These molecules comprise both hydrophilic and hydrophobic moieties of varying solubilities. In this review, several pathogenic microbes such as and spp. have been evaluated. Also, the development of a proper niosomal formulation for the required application was discussed. This review also reviews that an optimal formulation is dependent on several aspects, including the choice of nonionic surfactant, fabrication process, and fabrication parameters. Finally, this review will give information on the effectiveness of niosomes in treating acute microbial infections, the mechanism of action of niosomes in combating microbial pathogens, and the advantages of using niosomes over other treatment modalities.
Topics: Liposomes; Drug Delivery Systems; Anesthetics, General; Candida; Drug-Related Side Effects and Adverse Reactions
PubMed: 37621700
DOI: 10.1155/2023/9933283 -
International Journal of Molecular... Dec 2023The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal...
The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.
Topics: Mice; Animals; Swine; Hydrogels; Decellularized Extracellular Matrix; Dental Pulp; Mice, Nude; Regeneration; Tissue Scaffolds; Tissue Engineering; Extracellular Matrix
PubMed: 38139310
DOI: 10.3390/ijms242417483 -
ACS Biomaterials Science & Engineering Nov 2023Paper is an ideal candidate for the development of new disposable diagnostic devices because it is a low-cost material, allows transport of the liquid on the device by...
Paper is an ideal candidate for the development of new disposable diagnostic devices because it is a low-cost material, allows transport of the liquid on the device by capillary action, and is environmentally friendly. Today, colorimetric analysis is most often used as a detection method for rapid tests (test strips or lateral flow devices) but usually gives only qualitative results and is limited by a relatively high detection threshold. Here, we describe studies using fluorescence as a readout tool for paper-based diagnostics. We study how the optical readout is affected by light transmission, scattering, and fluorescence as a function of paper characteristics such as thickness (grammage), water content, autofluorescence, and paper type/composition. We show that paper-based fluorescence analysis allows better optical readout compared to that of nitrocellulose, which is currently the material of choice in colorimetric assays. To reduce the loss of analyte molecules (e.g., proteins) due to adsorption to the paper surface, we coat the paper fibers with a protein-repellent hydrogel. For this purpose, we use hydrophilic copolymers consisting of ,-dimethyl acrylamide and a benzophenone-based cross-linker, which are photochemically transformed into a fiber-attached polymer hydrogel on the paper fiber surfaces in situ. We show that the combination of fluorescence detection and the use of a protein-repellent coating enables sensitive paper-based analysis. Finally, the success of the strategy is demonstrated by using a simple LFD application as an example.
Topics: Paper; Microfluidic Analytical Techniques; Proteins; Hydrogels
PubMed: 37875260
DOI: 10.1021/acsbiomaterials.3c00736 -
International Journal of Pharmaceutics Jun 2024Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the... (Review)
Review
Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.
Topics: Humans; Animals; Drug Carriers; Administration, Ophthalmic; Eye; Drug Delivery Systems; Nanoparticles; Eye Diseases; Nanoparticle Drug Delivery System; Biological Availability; Drug Liberation
PubMed: 38703931
DOI: 10.1016/j.ijpharm.2024.124192 -
European Journal of Pharmaceutical... Sep 2023Pirfenidone (PFND) is a recommended oral drug used to treat idiopathic pulmonary fibrosis, but have low bioavailability and high hepatotoxicity. The study, therefore,...
Pirfenidone (PFND) is a recommended oral drug used to treat idiopathic pulmonary fibrosis, but have low bioavailability and high hepatotoxicity. The study, therefore, seeks to improve the therapeutic activities of the drug via increased bioavailability and reduced associated side effects by developing a novel drug delivery system. The electrostatic spray technology was used to prepare a sustained release pirfenidone-loaded microsphere dry powder inhalation with PEG-modified chitosan (PFND-mPEG-CS-MS). The entrapment efficiency, drug loading, and in vitro cumulative drug release rate (at 24 h and with a sustained release effect) of PFND-mPEG-CS-MS were 77.35±3.01%, 11.45±0.64%, and 90.4%, respectively. The Carr's index of PFND-mPEG-CS-MS powder was 17.074±2.163% with a theoretical mass median aerodynamic diameter (MMAD) of 0.99±0.07 μm, and a moisture absorption weight gain rate (R) of 4.61±0.72%. The emptying rate, pulmonary deposition rate (fine particle fraction) and actual mass median aerodynamic diameter (MMAD) were 90%∼95%, 48.72±7.04% and 3.10±0.16 μm, respectively. MTT bioassay showed that mPEG-CS-MS (200 μg/mL) had good biocompatibility (RGR = 90.25%) and PFND-mPEG-CS-MS (200 μg/mL) had significant inhibitory activity (RGR = 49.82%) on fibroblast growth. The pharmacokinetic data revealed that the t (5.02 h) and MRT (10.66 h) of PFND-mPEG-CS-MS were prolonged compared with the free PFND (t, 1.67 h; MRT, 2.71 h). The pharmacodynamic results also showed that the formulated-drug group had slight pathological changes, lower lung hydroxyproline content, and reduced hepatotoxicity compared with the free-drug group. The PFND-mPEG-CS-MS further significantly down-regulated TGF-β cytokines, Collagen I, and α-SMA protein expression levels compared with the free drug. The findings indicated that the PFND-mPEG-CS-MS had a good sustained release effect, enhanced bioavailability, decreased toxicity, and increased anti-fibrotic activities.
Topics: Humans; Powders; Delayed-Action Preparations; Microspheres; Idiopathic Pulmonary Fibrosis; Chemical and Drug Induced Liver Injury; Administration, Inhalation; Particle Size
PubMed: 37356463
DOI: 10.1016/j.ejps.2023.106509 -
Journal of Pharmaceutical Sciences Jul 2024The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure... (Review)
Review
The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure therapeutic efficacy, safety, and tolerability in paediatric patients, who have specific physiological needs and characteristics. In recent years, there has been a significant increase in attention towards this area, driven by the need to improve drug administration to children and ensure optimal and specific treatments. Technological innovation has played a crucial role in meeting these requirements, opening new frontiers in the design and production of paediatric pharmaceutical forms. In particular, three emerging technologies have garnered considerable interest and attention within the scientific and industrial community: 3D printing, prilling/vibration, and microfluidics. These technologies offer advanced approaches for the design, production, and customization of paediatric pharmaceutical forms, allowing for more precise dosage modulation, improved solubility, and greater drug acceptability. In this review, we delve into these cutting-edge technologies and their impact on the production of paediatric pharmaceutical forms. We analyse their potential, associated challenges, and recent developments, providing a comprehensive overview of the opportunities that these innovative methodologies offer to the pharmaceutical sector. We examine different pharmaceutical forms generated using these techniques, evaluating their advantages and disadvantages.
Topics: Printing, Three-Dimensional; Humans; Child; Microfluidics; Dosage Forms; Technology, Pharmaceutical; Pediatrics; Pharmaceutical Preparations; Drug Compounding; Chemistry, Pharmaceutical; Solubility
PubMed: 38582283
DOI: 10.1016/j.xphs.2024.04.001