Hyaluronic Acid-Based Hybrid Nanoparticles as Promising Carriers for the Intranasal Administration of Dimethyl Fumarate.

Purpose: Dimethyl fumarate (DMF), the first-line oral therapy for relapsing-remitting multiple sclerosis, is rapidly metabolized into monomethyl fumarate. The DMF oral administration provokes gastrointestinal discomfort causing treatment withdrawal. The present study aimed to develop an innovative formulation for DMF nasal administration.

Supramolecular delivery systems for polyphenols: A green approach to predict in vivo permeability through an in vitro setup.

The use of in vitro markers able to reproduce the in vivo permeability and diffusivity of orally administered drugs, could represent an innovative starting point for the formulation of delivery systems, in particular for low soluble and low permeable drugs belonging to BCS class II and IV. Considering the great interest in the green pharmaceutical approaches and the increasing use of natural molecules as novel therapeutic drugs, in this study, rutin, hesperidin and curcumin have been selected as lipophilic model drugs to investigate their possible enhancement of their permeability and bioavailability after oral administration. As the low solubility of the three drugs hinders their application, β-cyclodextrins (CD), amphiphilic natural moieties able to form stable inclusion complexes, have been considered to promote their solubilization.

Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA).

In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e.

Interpreting permeability as a function of free drug fraction: The case studies of cyclodextrins and liposomes.

In order to solubilize poorly soluble active pharmaceutical ingredients, various strategies have been implemented over the years, including the use of nanocarriers, such as cyclodextrins and liposomes. However, improving a drug's apparent solubility does not always translate to enhanced bioavailability. This work aimed to investigate to which extent complexation with cyclodextrins and incorporation into liposomes influence drug in vitro permeability and to find a mechanistic description of the permeation process.

Design and Characterization of an Ethosomal Gel Encapsulating Rosehip Extract.

Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach.

Commercially Available Cell-Free Permeability Tests for Industrial Drug Development: Increased Sustainability through Reduction of In Vivo Studies.

Replacing in vivo with in vitro studies can increase sustainability in the development of medicines. This principle has already been applied in the biowaiver approach based on the biopharmaceutical classification system, BCS. A biowaiver is a regulatory process in which a drug is approved based on evidence of in vitro equivalence, i.

Validation and testing of a new artificial biomimetic barrier for estimation of transdermal drug absorption.

Human skin remains the most reliable model for studying the transdermal permeation of active compounds. Due to the limited source, porcine skin has been used extensively for performing penetration tests. Performing penetration studies by using human and animal skin, however, would also involve a series of ethical issues and restrictions.

Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin.

The objective of this work was to optimize a thermosensitive in situ gelling formulation to improve intranasal and nose-to-brain delivery of the antiepileptic drug carbamazepine (CBZ). A preliminary procedure of vehicles obtained just mixing different fractions of poloxamer 407 (P407) and poloxamer 188 (P188) revealed preparations with phase transition temperatures, times to gelation and pH values suitable for nasal delivery. Subsequently, the mucoadhesive properties of the most promising formulations were tuned by adding hydroxypropylmethylcellulose types of different viscosity grades, and the effect of the adhesive polymers was evaluated by testing in vitro time and strength of mucoadhesion on specimens of sheep nasal mucosa.

Modelling drug diffusion through unstirred water layers allows real-time quantification of free/loaded drug fractions and release kinetics from colloidal-based formulations.

The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the drug. One mechanism that still lacks a proper interpretation is the kinetics of drug release from nanocarriers.

Human Biosurfactants as Natural Excipients for Nasal Drug Delivery of Hydrocortisone.

The inclusion of a chemical permeation enhancer in a dosage form is considered an effective approach to improve absorption across the nasal mucosa. Herein we evaluated the possibility of exploiting biosurfactants (BS) produced by BC9 as innovative natural excipients to improve nasal delivery of hydrocortisone (HC). BC9-BS ability to improve HC solubility and the BS mucoadhesive potential were investigated using the surfactant at a concentration below and above the critical micelle concentration (CMC).

Towards a better mechanistic comprehension of drug permeation and absorption: Introducing the diffusion-partitioning interplay.

The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption.

Impact of Mucin on Drug Diffusion: Development of a Straightforward in Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin.

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.

Imported human Schistosoma japonicum: A report on two cases in Filipino migrants present in Italy and a systematic review of literature.

Background: Schistosoma japonicum is endemic in the Philippines, China, and Indonesia, and is the third-most common schistosoma species. The infection can be asymptomatic for years but, if left untreated, can lead to irreversible complications.

Method: We report the results of a systematic review of the literature on imported S.

Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes.

The aim of this work was to clarify the dynamics behind the influence of ionic strength on the changes in drug release from large unilamellar vesicles (LUVs). For this purpose, we have investigated the transport of two different model drugs (caffeine and hydrocortisone) formulated into liposomes through different types of barriers with different retention properties (regenerated cellulose and the newly introduced biomimetic barrier, Permeapad®). Drug release from liposomes was studied utilizing the standard Franz diffusion cells.

Studying the effect of solubilizing agents on drug diffusion through the unstirred water layer (UWL) by localized spectroscopy.

An experimental/computational approach has been successfully applied in order to study the effect of solubilizing vehicles (cyclodextrins and liposomes) on the passive diffusion of four active pharmaceutical ingredients (API) of different nature (hydrophilic, ionizable and lipophilic) through an unstirred water layer (UWL) model. This approach allowed the measurement of flux changes through the UWL and the computational calculation of different parameters relevant to interpret the interplay within solubilizing vehicles and UWL diffusion. In the case of cyclodextrin, this approach allowed the determination of free drug diffusivity (D), bound drug diffusivity (D) and the equilibrium constant (K).

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery.

Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within minutes. However, the nasal mucosa properties (e.

Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements.

The diffusion coefficient (also known as diffusivity) of an active pharmaceutical ingredient (API) is a fundamental physicochemical parameter that affects passive diffusion through biological barriers and, as a consequence, bioavailability and biodistribution. However, this parameter is often neglected, and it is quite difficult to find diffusion coefficients of small molecules of pharmaceutical relevance in the literature. The available methods to measure diffusion coefficients of drugs all suffer from limitations that range from poor sensitivity to high selectivity of the measurements or the need for dedicated instrumentation.

Influence of the environmental tonicity perturbations on the release of model compounds from large unilamellar vesicles (LUVs): A mechanistic investigation.

In this work, the influence of environmental tonicity perturbations on the size and release kinetics of model markers from liposomes (calcein and rhodamine) was investigated. Large unilamellar vesicles (LUVs) were prepared from a mixture composed of organic solvents containing dissolved phosphatidylcholine and phosphate buffered saline (PBS, pH 7.4).

Novel in situ gel-forming solid dosage form (gfSDF) prepared by the simple syringe-based moulding: A screening study.

The aim of this study was to prepare and optimize a novel type of in situ gel-forming solid dosage form (gfSDF) to be used in the treatment of mucosal/skin ulcerations. For this purpose, a simple but reliable syringe-based hot melt/moulding method was employed. Chloramphenicol (antibiotic) and ibuprofen (anti-inflammatory) were chosen as model active pharmaceutical ingredients (APIs) to be loaded into the gfSDFs.

The Potential of Cyclodextrins as Novel Active Pharmaceutical Ingredients: A Short Overview.

Cyclodextrins (CDs) are cyclic oligosaccharides of natural origin that were discovered more than 100 years ago. The peculiar cone-like conformation of the sugar ring, expressing a lipophilic cavity and a hydrophilic external surface, allows these substances to spontaneously complex poorly soluble compounds in an aqueous environment. For more than 50 years, these substances have found applicability in the pharmaceutical and food industries as solubilizing agents for poorly soluble chemical entities.

β-CD-dextran polymer for efficient sequestration of cholesterol from phospholipid bilayers: Mechanistic and safe-toxicity investigations.

The aim of this work was to investigate the suitability of β-cyclodextrin-dextran (BCD-dextran) polymer as cholesterol sequestering agent in vitro. For this purpose, BCD-dextran-cholesterol complexation was studied by phase solubility studies as well as with a specifically designed in vitro model based on giant unilamellar vesicles (GUVs) to evaluate the ability of this polymer to sequestrate cholesterol from phospholipid bilayers. Cholesterol-sequestering ability of BCD-dextran was also investigated on different cell lines relevant for the hematopoietic system and results were correlated to cells toxicity.

Permeapad™ for investigation of passive drug permeability: The effect of surfactants, co-solvents and simulated intestinal fluids (FaSSIF and FeSSIF).

The aim of the present work was to investigate the potential of the new and innovative artificial barrier, Permeapad™, when exposed to surfactants and co-solvents, often employed for poorly water soluble compounds. The barrier was in addition also exposed to fasted and fed state simulated intestinal fluids versions 1 and 2 (FaSSIF and FeSSIF), all of which the Permeapad™ barrier was compatible with based upon relative comparison of the permeability of the hydrophilic marker calcein in phosphate buffer. The new barrier therefore holds a huge potential due to its functional stability and robustness.

New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs.

In this work the suitability of a newly invented physical patch comprising a biomimetic barrier (named Permeapad™) for drug permeability tests has been investigated. Exemplars of Permeapad™ were adapted to Franz diffusion cells and apparent permeability (Papp) of a series of drugs were measured and compared with calculated partition coefficients (logPcal) of the investigated drugs as well as literature reference values obtained from Parallel Artificial Membrane Permeation Assay (PAMPA) and the cellular based method Caco-2. Moreover, tightness of the barrier to hydrophilic marker's permeation, resistance of these barriers to proton permeation (pH changes) and shelf-life functionality were also investigated.

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods.

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method.