Agnese Gagliardi

Background/Objectives: Poloxamine 908 (P908), an amphiphilic block copolymer with thermo- and pH-responsive properties, was demonstrated to be a biomaterial that can be employed for the development of injectable hydrogels. The present study aimed to investigate the influence of nanoparticles with different chemical compositions and surface properties on the properties of P908 hydrogels. Methods: Poloxamer 188 (P188)-PLGA, P188-zein and sodium deoxycholate (SD)-zein nanoparticles obtained by nanoprecipitation were incorporated into 30% (w/w) P908 hydrogels using the cold preparation method. The formulations were characterized by rheological analysis, dissolution studies, FT-IR spectroscopy, in vitro release analysis using rutin as a model compound, and DPPH radical scavenging assay to evaluate the bioactivity of nanoparticles contained within the hydrogel matrix. Results: The incorporation of nanosystems preserved the injectability and thermoresponsive behavior of P908 hydrogels and affected their rheological and dissolution properties in different ways. P188-PLGA NPs increased viscosity by approximately 23%, whereas P188-zein NPs caused a slight decrease of approximately 9%, compared with plain P908 at 37 °C and 1 s⁻¹. Both formulations showed a moderate increase in T_sol–gel, reaching 28.5 and 28.8 °C, respectively, compared with 26.4 °C for plain P908 systems. A more pronounced effect was observed with SD-zein NPs, which reduced viscosity by approximately 29% and shifted T_sol–gel to 33.9 °C. Moreover, SD-zein NPs enhanced hydrogel dissolution under acidic conditions, with complete dissolution occurring after 6 h at pH 5.0 compared with 8 h at pH 7.0. FT-IR demonstrated the effective inclusion of the colloidal systems within the P908 matrix. Nanocomposite hydrogels provided a more sustained release of rutin with respect to that obtained without the copolymeric matrix, with positively charged P188-zein nanosystems showing an enhanced release at acidic pH, likely due to electrostatic repulsion with the protonated P908 network. DPPH assay confirmed that the inclusion of rutin-loaded nanoparticles into P908 hydrogels preserved the antioxidant activity of the active compound, with a slight increase in radical scavenging capacity, due to the intrinsic mild antioxidant capacity of the copolymeric matrix. Conclusions: P908 is a suitable biomaterial to develop nanocomposite hydrogels. The composition and surface properties of nanoparticles allow for the modulation of hydrogel features, enabling the design of therapeutic formulations with tailored rheological properties and characteristics of drug release.

In ophthalmology, developing effective drug delivery systems is crucial to overcome anatomical and physiological barriers, such as rapid tear turnover and blinking, which limit the efficacy of conventional formulations like eye drops. Poloxamers, especially the derivatives 407 (P407) and 188, are amphiphilic triblock copolymers characterized by an intriguing thermo-reversible behavior, making them ideal candidates for the development of in situ hydrogels for ocular applications. Various thermo-sensitive poloxamer-based hydrogels were designed to be easily instilled as liquids at room temperature, gelling promptly upon contact with the corneal surface. These systems promoted a controlled release of active compounds, significantly improving their adhesion to the ocular surface. This review discusses the most relevant scientific literature on the topic, with particular attention to studies published in recent years. The results demonstrated that poloxamer formulations are capable of overcoming typical ocular barriers, thereby increasing drug bioavailability. The intrinsic biocompatibility of poloxamers contributes to the safety and tolerability of the system. Furthermore, P407 showed additional wound healing features. The combination of biocompatibility and thermo-reversible behavior makes poloxamer-based hydrogels a promising platform for the development of innovative ocular drug delivery systems able to enhance therapeutic efficacy and patient comfort.

Nanotechnology has been widely employed in the field of cosmeceuticals, promoting the development of innovative cosmetic formulations characterized by notable pharmacological activity. The use of nanocosmeceuticals allows for better skin penetration of active compounds, their controlled release over time, and greater physico-chemical stability. Chitosan nanoparticles have generated significant interest in the scientific community as dermal and transdermal delivery systems for natural compounds. In particular, the encapsulation of polyphenols within chitosan nanosystems has been proposed as a method to enhance the effectiveness of bioactives in cosmeceutical formulations. This review discusses the most relevant scientific literature on the topic, with particular attention to studies published in recent years. Chitosan-based nanosystems improve the stability, bioavailability, and skin compatibility of polyphenols, offering promising solutions for the prevention and treatment of skin disorders due to their antioxidant and anti-inflammatory properties. This review provides a comprehensive update on the development of chitosan nanoparticles containing polyphenols and their potential clinical applications, highlighting the role of these systems as nanocosmeceuticals.

Niaprazine is a sedative-hypnotic drug initially developed as an antihistamine and used for its notable sedative effects, particularly in children. Following its withdrawal from the market by the producer, the drug has been administered as magistral formulations available in syrup form, but there are several important disadvantages to this, including instability, taste issues, lack of controlled release, and the potential for unreliable dosing due to incomplete swallowing. There is also an increased risk of dental caries, as well as the fact that these formulations are not suitable for children who suffer from diabetes. The purpose of the current investigation is to prepare and characterize xanthan gum-based gels for the oral administration of niaprazine. Niaprazine gels appear as transparent-whiteish, non-sticky substances, with the drug uniformly dispersed throughout the systems. They are also stable over time. Dynamic rheology revealed their advantageous shear-thinning properties, which enable the formulation to be flexibly dosed orally through administration via syringe. During experimentation, the evaluation of the mucoadhesion features and the in vitro drug release profile were also performed. The results demonstrate that the formulation may represent an alternative to niaprazine syrup, allowing easy preparation, administration, and increased compliance in various categories of patients, including pediatric.

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery.

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests.

Background: Gliadins have aroused significant interest in the last decade as suitable biomaterials for food and pharmaceutical applications. In particular, the oral route is the preferred method of administration for gliadin-based formulations, due to the affinity of this biomaterial for the gut mucosa. However, up to now, this has been demonstrated only by means of in vivo or ex vivo studies. Methods: This is why, in this study, various in vitro techniques were employed in order to evaluate the ability of polymeric nanoparticles, made up of a commercial grade of the protein and an etheric surfactant, to interact with porcine gastric mucin. The nanosystems were also used for the encapsulation of thiamine hydrochloride, used as a model of a micronutrient. Results: The resulting systems were characterized by a mean diameter of ~160–170 nm, a narrow size distribution when 0.2–0.6 mg/mL of thiamine was used, and an encapsulation efficiency between 30 and 45% of the drug initially employed. The incubation of the gliadin nanosystems with various concentrations of porcine gastric mucin evidenced the ability of the carriers to interact with the mucus glycoprotein, showing a decreased Zeta potential after a 4 h incubation (from ~−30 to −40 mV), while demonstrating that the encapsulation of the drug did not affect its bioadhesive features. Conclusions: Altogether, these data support the conceivable application of gliadin nanoparticles as formulations for the oral administration of bioactive compounds.

Editorial: Protein nanoparticles: characterization and pharmaceutical application

A biodegradable and biocompatible polymeric matrix made up of poly(d,l-lactide-co-glycolide) (PLGA) was used for the simultaneous delivery of rutin and the (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide derivative (URB894). The goal was to exploit the well-known radical scavenging properties of rutin and the antioxidant features recently reported for the molecules belonging to the class of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors, such as URB894. The use of the compounds, both as single agents or in association promoted the development of negatively-charged nanosystems characterized by a narrow size distribution and an average diameter of ~200 nm when 0.2–0.6 mg/mL of rutin or URB894 were used. The obtained multidrug carriers evidenced an entrapment efficiency of ~50% and 40% when 0.4 and 0.6 mg/mL of rutin and URB894 were associated during the sample preparation, respectively. The multidrug formulation evidenced an improved in vitro dose-dependent protective effect against H₂O₂-related oxidative stress with respect to that of the nanosystems containing the active compounds as a single agent, confirming the rationale of using the co-encapsulation approach to obtain a novel antioxidant nanomedicine.

Doxorubicin hydrochloride (DOX) is a well-known antitumor drug used as first line treatment for many types of malignancies. Despite its clinical relevance, the administration of the compound is negatively affected by dose-dependent off-target toxicity phenomena. Nanotechnology has helped to overcome these important limitations by improving the therapeutic index of the bioactive and promoting the translation of novel nanomedicines into clinical practice. Herein, nanoparticles made up of wheat gliadin and stabilized by polyoxyethylene (2) oleyl ether were investigated for the first time as carriers of DOX. The encapsulation of the compound did not significantly affect the physico-chemical features of the gliadin nanoparticles (GNPs), which evidenced a mean diameter of ~180 nm, a polydispersity index < 0.2 and a negative surface charge. The nanosystems demonstrated great stability regarding temperature (25–50 °C) and were able to retain high amounts of drug, allowing its prolonged and sustained release for up to a week. In vitro viability assay performed against breast cancer cells demonstrated that the nanoencapsulation of DOX modulated the cytotoxicity of the bioactive as a function of the incubation time with respect to the free form of the drug. The results demonstrate the potential use of GNPs as carriers of hydrophilic antitumor compounds.