Critical assessment of purification processes for the robust production of polymeric nanomedicine.

Polymeric nanoparticles are among the most widely used nanocarriers for delivering therapeutic molecules. However, their synthesis processes often generate undesirable impurities that could be toxic and challenging to eliminate. In this study, we compared three purification techniques - centrifugation, dialysis, and tangential flow filtration (TFF) - to evaluate their efficacy in removing residual drug, surfactant, and solvent while preserving the nanoparticles' physicochemical features (hydrodynamic size, zeta potential, polydispersity index).

Impact of the crystal size of crystalline active pharmaceutical compounds on loading into microneedles.

Microneedle (MN) technology offers a promising platform for the delivery of a wide variety of active pharmaceutical compounds into and/or through the skin. Yet, the low loading capacity of MNs limits their clinical translation. The solid state of loaded compounds, crystallinity versus amorphousness and crystal size of the former, could greatly affect their loading.

Purification processes of polymeric nanoparticles: How to improve their clinical translation?

Polymeric nanoparticles, as revolutionary nanomedicines, have offered a new class of diagnostic and therapeutic solutions for a multitude of diseases. With its immense potential, the world witnesses the new age of nanotechnology after the COVID-19 vaccines were developed based on nanotechnology. Even though there are countless benchtop research studies in the nanotechnology world, their integration into commercially available technologies is still restricted.

New trends for osteoarthritis: Biomaterials, models and modeling.

The burden of osteoarthritis (OA), one of the major causes of functional disabilities in humans and animals, continues to increase worldwide while no disease-modifying OA drugs (DMOADs) that either slow down or reverse disease progression have been made available. Here, we provide a brief overview of recent advances in: designing new OA drug delivery approaches, focusing on lubrication-based biomaterials and drug delivery systems, such as hydrogels, liposomes, dendrimers, micro- and nanoparticles; using either large (horse) or small (zebrafish) relevant animal models to evaluate new therapeutic strategies; and OA in vitro modeling, focusing on 3D (organoid) models of cartilage regarding the Replace, Reduce and Refine (3R) principle of animal experimentation.

Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage.

Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation.

Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization.

This study assessed the stability of six extemporaneously compounded hydroxyurea oral liquids stored at room temperature. Hydroxyurea oral liquids (100 mg/mL) were prepared using three different mixing methods (mortar, mixer or QuartetRx) from either bulk powder, capsule content, or whole capsules. Two brands of capsules were tested in this study.

Tailoring PEGylated nanoparticle surface modulates inflammatory response in vascular endothelial cells.

Polymer nanoparticles (NPs) are extensively studied as drug delivery systems for various therapeutic indications, including drug and imaging agent delivery to the brain. Despite intensive research, their toxicological profile has yet to be fully characterized. In particular, the more subtle effects of nanomaterials on inflammatory processes have scarcely been investigated.

Stability evaluation of compounded clonidine hydrochloride oral liquids based on a solid-phase extraction HPLC-UV method.

The present study aimed to assess the stability of clonidine hydrochloride oral liquids (20-μg/mL) prepared from two different generic tablets in Ora-Blend and stored in amber plastic bottles. Physical and chemical stabilities were evaluated over a period of 90 days at 25°C. Analytical challenges were overcome with the development of a new extraction procedure based on solid phase extraction to ensure efficient clonidine hydrochloride quantification.

Lipid Coating of Chitosan Nanogels for Improved Colloidal Stability and In Vitro Biocompatibility.

Chitosan-based carriers have coined their position as delivery agents. When assembled with polyanions into nanogels (NG), these vectors have enabled the delivery of drugs, genes, and proteins to a myriad of applications. However, the chemical and colloidal instability of chitosan nanoformulations in physiologically compatible media prejudices in vitro biocompatibility and, thus, scale-up applications.

Preparation and characterization of 12-HSA-based organogels as injectable implants for the controlled delivery of hydrophilic and lipophilic therapeutic agents.

Organogels prepared with low molecular weight organogelators to structure liquid oils represent excellent matrices for the controlled delivery of a wide variety of drug molecules. Although studies on organogel systems are reported in the literature, relatively few investigate their potential as gels formed in situ intended for drug delivery. This study reports the development of injectable subcutaneous 12- hydroxystearic acid (12-HSA) organogels for the delivery of both lipophilic and hydrophilic drugs.

Erratum: Puscas, I.; et al. IVIVC Assessment of Two Mouse Brain Endothelial Cell Models for Drug Screening. 2019, , 587.

The authors wish to make the following corrections to this paper [...

Isolation of endothelial cells, pericytes and astrocytes from mouse brain.

Primary cell isolation from the central nervous system (CNS) has allowed fundamental understanding of blood-brain barrier (BBB) properties. However, poorly described isolation techniques or suboptimal cellular purity has been a weak point of some published scientific articles. Here, we describe in detail how to isolate and enrich, using a common approach, endothelial cells (ECs) from adult mouse brains, as well as pericytes (PCs) and astrocytes (ACs) from newborn mouse brains.

IVIVC Assessment of Two Mouse Brain Endothelial Cell Models for Drug Screening.

Since most preclinical drug permeability assays across the blood-brain barrier (BBB) are still evaluated in rodents, we compared an in vitro mouse primary endothelial cell model to the mouse b.End3 and the acellular parallel artificial membrane permeability assay (PAMPA) models for drug screening purposes. The mRNA expression of key feature membrane proteins of primary and bEnd.

PLGA nanoparticles optimized by Box-Behnken for efficient encapsulation of therapeutic Cymbopogon citratus essential oil.

This study aimed to optimize Cymbopogon citratus essential oil loaded into PLGA-nanoparticles by investigating the effect of processing variables (sonication time, ultrasound power, and essential oil/polymer ratio) on encapsulation efficiency and particle mean hydrodynamic diameter using Box-Behnken design. Nanoparticles were prepared by an emulsification/solvent diffusion method and physicochemically characterized by FTIR, DSC and TGA/DTA. Cytotoxicity was evaluated in human HaCat keratinocytes by WST-1 and LDH assays.

Development of a safe and versatile suspension vehicle for pediatric use: Formulation development.

This project aimed to develop a suspension vehicle specifically designed for pediatric use. Excipients were selected according to their safety and recorded use in pediatrics. Two suspension vehicles were formulated at neutral and acidic pH.

Tailored Nanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas aeruginosa: A Comparative Study.

Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time, and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa.

Length of surface PEG modulates nanocarrier transcytosis across brain vascular endothelial cells.

Diblock PLA-PEG nanoparticles were produced to establish the role of PEG chain length on brain vascular endothelial cell transcytosis. 100-nm nanoparticles tagged with fluorescent pyrene butanol and coated with PEG chains (Mw: 1-10 kDa), at similar PEG surface density, were used to study endocytosis and transcytosis phenomena on mouse vascular endothelial cell monolayers. The transport mechanisms were then investigated through inhibitory processes.

Quantification of peptides in human synovial fluid using liquid chromatography-tandem mass spectrometry.

A method to explore the stability of two anti-inflammatory peptides in human synovial fluid (HSF) has been developed and validated using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The two peptides are BQ123 Cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu, Mw = 610.7) and R-954 (AcOrn[Oic, (αMe)Phe, DβNal, Ile]desArg-bradykinin, Mw = 1194.

Organogels, promising drug delivery systems: an update of state-of-the-art and recent applications.

Organogels are semi-solid systems with an organic liquid phase immobilized by a three-dimensional network composed of self-assembled, crosslinked or entangled gelator fibers. Organogel applications are various, including chemistry, pharmaceuticals, cosmetics, biotechnologies and food technology. In pharmacology, they are used as drug and vaccine delivery platforms for active ingredients via diverse routes such as transdermal, oral and parenteral.

Stability of gabapentin in extemporaneously compounded oral suspensions.

This study reports the stability of extemporaneously prepared gabapentin oral suspensions prepared at 100 mg/mL from bulk drug and capsules in either Oral Mix or Oral Mix SF suspending vehicles. Suspensions were packaged in amber plastic bottles and amber plastic syringes at 25°C / 60%RH for up to 90 days. Throughout the study period, the following tests were performed to evaluate the stability of the preparations: organoleptic inspection to detect homogeneity, color or odor changes; pH measurements; and gabapentin assay using a stability-indicating HPLC-UV method.

Stability of Diazoxide in Extemporaneously Compounded Oral Suspensions.

The objective of this study was to evaluate the stability of diazoxide in extemporaneously compounded oral suspensions. Oral suspensions of diazoxide 10 mg/mL were prepared from either bulk drug or capsules dispersed in either Oral Mix or Oral Mix Sugar Free. These suspensions were stored at 5°C and 25°C/60%RH in bottles and oral syringes for a total of 90 days.

Neuronal Uptake and Neuroprotective Properties of Curcumin-Loaded Nanoparticles on SK-N-SH Cell Line: Role of Poly(lactide-co-glycolide) Polymeric Matrix Composition.

Curcumin, a neuroprotective agent with promising therapeutic approach has poor brain bioavailability. Herein, we demonstrate that curcumin-encapsulated poly(lactide-co-glycolide) (PLGA) 50:50 nanoparticles (NPs-Cur 50:50) are able to prevent the phosphorylation of Akt and Tau proteins in SK-N-SH cells induced by H2O2 and display higher anti-inflammatory and antioxidant activities than free curcumin. PLGA can display various physicochemical and degradation characteristics for controlled drug release applications according to the matrix used.

Encapsulated Ruthenium(II) Complexes in Biocompatible Poly(d,l-lactide-co-glycolide) Nanoparticles for Application in Photodynamic Therapy.

The elaboration, characterisation and efficiency of potential two-photon-excited photodynamic therapy (PDT) treatment of new poly(d,l-lactide-co-glycolide) nanoparticles loaded with ruthenium(II) complexs are presented. The materials are based on the encapsulation of Ru complexes through an all-biocompatible process. The size of the nanoparticles is around 100 nm.

Etoposide encapsulation in surface-modified poly(lactide-co-glycolide) nanoparticles strongly enhances glioma antitumor efficiency.

Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the blood-brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110-130 nm) using a fully biocompatible nanoprecipitation technique.