Hyaluronan nanoplatelets exhibit extended residence time compared to spherical and ellipsoidal nanomaterials with equivalent surface potentials and volumes after oral delivery in rats.

The physicochemical properties of colloidal particles-such as size, surface properties, and morphology-play a crucial role in determining their behaviors and transit through the gastrointestinal (GI) tract. While some data exist for nonspherical nanomaterials (NMs) composed of silica or polystyrene, there is limited understanding of NMs composed of polysaccharides and polymers. This study explores the fate and GI tract residence time of hyaluronan-based NMs with distinctive hexagonal morphology and flat surfaces (nanoplatelets) following administration to rats.

A nanomedicine approach for the treatment of long-lasting pain.

This study explores the potential of a nanomedicine approach, using Leu-enkephalin-squalene nanoparticles (LENK-SQ NPs) for managing long-lasting pain. It was observed that the nanomedicine significantly improved the pharmacological efficacy of the Leu-enkephalin, a fast metabolized neuropeptide, in a rat model of acute inflammatory pain, providing local analgesic effect, while minimizing potential systemic side effects by circumventing central nervous system. The LENK-SQ NPs were tested in a rat model of postoperative pain (Brennan's rodent plantar incision model) using continuous infusion via Alzet® pump, with an additional bolus injection.

Overcoming Solubility Challenges: Liposomal isoCoQ-Carbazole as a Promising Anti-Tumor Agent for Inoperable and Radiation-Insensitive cancers.

This study evaluated the potential of isoCoQ-Carbazole, a diheterocyclic analog of isoCA-4, as an anti-tumor agent. To overcome its low aqueous solubility, liposomes were developed as a delivery system for the compound. In vitro experiments showed that loaded liposomes exhibited similar activity to the free form on multiple human tumor cell lines.

Assessment of Squalene-Adenosine Nanoparticles in Two Rodent Models of Cardiac Ischemia-Reperfusion.

Reperfusion injuries after a period of cardiac ischemia are known to lead to pathological modifications or even death. Among the different therapeutic options proposed, adenosine, a small molecule with platelet anti-aggregate and anti-inflammatory properties, has shown encouraging results in clinical trials. However, its clinical use is severely limited because of its very short half-life in the bloodstream.

Diclofenac prodrugs nanoparticles: An alternative and efficient treatment for rheumatoid arthritis?

We have synthesized new lipidic prodrugs of diclofenac by grafting aliphatic chains (C10, C12, C16 and C18) to diclofenac through an ester bond. Their molecular formulas were confirmed through HR-MS and the formation of ester bond by FTIR and NMR spectroscopy. Nanoparticles of the different prodrugs were successfully formulated using emulsion evaporation method and DSPE-PEG as the only excipient.

Hyaluronic acid-conjugated liposomes loaded with dexamethasone: A promising approach for the treatment of inflammatory diseases.

Dexamethasone is a well-known anti-inflammatory drug readily used to treat many lung diseases. However, its side effects and poor lower airway deposition and retention are significant limitations to its usage. In this work, we developed lipid nanoparticulate platforms loaded with dexamethasone and evaluated their behavior in inflammatory lung models in vitro and in vivo.

Hyaluronan nanoplatelets exert an intrinsic anti-inflammatory activity in a rat model of bladder painful syndrome/interstitial cystitis.

Glycosaminoglycan (GAG) replenishment therapy consists of the instillation of GAG solutions directly in the bladder to alleviate Bladder Painful Syndrome/Interstitial Cystitis (BPS/IC). However, several issues were reported with this strategy because the GAG solutions are rapidly eliminated from the bladder by spontaneous voiding, and GAG have low bioadhesive behaviors. Herein, GAG nanomaterials with typical flattened morphology were obtained by a self-assembly process.

Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis.

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain.

Interplay between mucus mobility and alveolar macrophage targeting of surface-modified liposomes.

Alveolar macrophages play a crucial role in the initiation and resolution of the immune response in the lungs. Pro-inflammatory M1 alveolar macrophages are an interesting target for treating inflammatory and infectious pulmonary diseases. One commune targeting strategy is to use nanoparticles conjugated with hyaluronic acid, which interact with CD44 overexpressed on the membrane of those cells.

A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs.

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections).

Biocompatible and Photostable Photoacoustic Contrast Agents as Nanoparticles Based on Bodipy Scaffold and Polylactide Polymers: Synthesis, Formulation, and Evaluation.

We have designed a new Bodipy scaffold for efficient photoacoustic (PA) imaging of nanoparticles commonly used as drug nanovectors. The new dye has an optimized absorption band in the near-infrared window in biological tissue and a low fluorescence quantum yield that leads to a good photoacoustic generation efficiency. After Bodipy-initiated ring-opening polymerization of lactide, the polylactide-Bodipy was formulated into PEGylated nanoparticles (NPs) by mixing with PLA-PEG at different concentrations.

Pharmacokinetics, biodistribution, and activity of Amphotericin B-loaded nanocochleates on the Leishmania donovani murine visceral leishmaniasis model.

Amphotericin B (AmB) is an effective drug to treat visceral leishmaniasis but its use is limited by its poor oral bioavailability. This article describes the in-vivo evaluation of AmB-loaded, lipid-based cochleate systems designed for the oral route. Two different cochleate formulations were studied: one based on the synthetic phospholipid dioleoylphosphatidylserine (DOPS) and another optimized formulation based on a naturally occurring phosphatidylserine (Lipoid PSP70) that would render the formulation more affordable in developing countries.

Stability, pharmacokinetics, and biodistribution in mice of the EPAC1 inhibitor (R)-CE3F4 entrapped in liposomes and lipid nanocapsules.

(R)-CE3F4, a specific inhibitor of EPAC1 (exchange protein directly activated by cAMP type 1), has been demonstrated in vitro and in vivo to reduce hypertrophic signaling contributing to heart failure or to control arrhythmia and has shown promise as a drug candidate. However, (R)-CE3F4 exhibits poor solubility in aqueous media and has shown sensitivity to enzyme hydrolysis in plasma. To overcome these issues, the drug was entrapped in liposomes and lipid nanocapsules.

Interspecies comparison of plasma metabolism and sample stabilization for quantitative bioanalyses: Application to (R)-CE3F4 in preclinical development, including metabolite identification by high-resolution mass spectrometry.

The CE3F4 is an inhibitor of the type 1 exchange protein directly activated by cAMP (EPAC1), which is involved in numerous signaling pathways. The inhibition of EPAC1 shows promising results in vitro and in vivo in different cardiac pathological situations like hypertrophic signaling, contributing to heart failure, or arrhythmia. An HPLC-UV method with a simple and fast sample treatment allowed the quantification of (R)-CE3F4.

Gemcitabine lipid prodrug nanoparticles: Switching the lipid moiety and changing the fate in the bloodstream.

A simple approach to achieve a lipoprotein (LP)-mediated drug delivery is to trigger the spontaneous drug insertion into endogenous lipoproteins in the bloodstream, by means of its chemical modification. Nanoparticles (NPs) made of the squalene-gemcitabine (SQGem) conjugate were found to have a high affinity for plasma lipoproteins while free gemcitabine did not, suggesting a key role of the lipid moiety in this event. Whether the drug conjugation to cholesterol, one of the major lipoprotein-transported lipids, could also promote an analogous interaction was a matter of question.

Transtympanic injection of a liposomal gel loaded with N-acetyl-L-cysteine: A relevant strategy to prevent damage induced by cochlear implantation in guinea pigs?

Patients with residual hearing can benefit from cochlear implantation. However, insertion can damage cochlear structures and generate oxidative stress harmful to auditory cells. The antioxidant N-acetyl-L-cysteine (NAC) is a precursor of glutathione (GSH), a powerful endogenous antioxidant.

Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents.

Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner.

Squalene-based nanoparticles for the targeting of atherosclerotic lesions.

Native low-density lipoproteins (LDL) naturally accumulate at atherosclerotic lesions and are thought to be among the main drivers of atherosclerosis progression. Numerous nanoparticular systems making use of recombinant lipoproteins have been developed for targeting atherosclerotic plaque. These innovative formulations often require complicated purification and synthesis procedures which limit their eventual translation to the clinics.