This study investigated the development of a genipin-crosslinked chitosan (CS)-based polyvinylpyrrolidone (PVP) hydrogel containing curcumin nanosuspensions (Cur-NSs) to promote wound healing in an excisional wound model. Cur-NSs were prepared, and a simplex centroid mixture design was employed to optimize hydrogel properties for high water absorption, degree of crosslinking, and sufficient toughness. The in vivo wound healing effect was tested in Wistar rats. The optimized hydrogel consisted of a 70:30 ratio of CS:PVP, crosslinked with a 2 % w/w genipin solution. It exhibited high swelling capability (486 %) while maintaining solidity, robustness, and durability. Incorporating 5 % w/w Cur-NSs resulted in a more compact structure, although with a reduction in swelling properties. The release kinetics of Cur from the hydrogel followed the Korsmeyer-Peppas Fickian diffusion model. In vitro biocompatibility studies demonstrated that the hydrogel was non-toxic to skin fibroblast cells. The in vivo experiment revealed a desirable wound healing rate with over 80 % recovery by day 7. Cur-NSs likely aided wound healing by reducing the inflammatory response and stimulating fibroblast proliferation. Additionally, the CS-based hydrogel provided a moist wound environment with hydration and gas transfer, further accelerating wound closure. These findings suggest that the Cur-NS-embedded hydrogel shows promise as a wound dressing material.

BACKGROUND: The presence of barnyardgrass poses a threat to global food security by reducing rice yields. Currently, herbicides are primarily applied for weed management. However, the effectiveness of herbicide deposition and uptake on barnyardgrass is limited as a consequence of the high wax content on leaves, low water solubility and extreme lipophilicity of herbicides. Therefore, it is imperative to develop novel formulations for efficient delivery of herbicides to improve herbicidal activity and reduce dosage.
RESULTS: We successfully prepared nanosuspension(s) (NS) of quinclorac through the wet media milling technique. This NS demonstrates excellent physical stability and maintains nanoscale during dose transfer. The deposition concentration and uptake concentration of NS on barnyardgrass were 3.84-4.47- and 2.11-2.58-fold greater than those traditional formulations, respectively. Moreover, the NS exhibited enhanced herbicidal activity against barnyardgrass at half the dosage required by conventional formulations without compromising rice safety.
CONCLUSIONS: These findings suggest that NS can effectively facilitate the delivery of hydrophobic and poorly water-soluble herbicide active ingredients, thereby enhancing their deposition, uptake and bioactivity. This study expands the potential application of NS in pesticide delivery, which can provide valuable support for optimizing pesticide utilization, improving economic efficiency and mitigating environmental risks. © 2024 Society of Chemical Industry.

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 μm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

This review article provides a comprehensive overview of the advancements in using nanosuspensions for controlled drug delivery in ophthalmology. It highlights the significance of ophthalmic drug delivery due to the prevalence of eye diseases and delves into various aspects of this field. The article explores molecular mechanisms, drugs used, and physiological factors affecting drug absorption. It also addresses challenges in treating both anterior and posterior eye segments and investigates the role of mucus in obstructing micro- and nanosuspensions. Nanosuspensions are presented as a promising approach to enhance drug solubility and absorption, covering formulation, stability, properties, and functionalization. The review discusses the pros and cons of using nanosuspensions for ocular drug delivery and covers their structure, preparation, characterization, and applications. Several graphical representations illustrate their role in treating various eye conditions. Specific drug categories like anti-inflammatory drugs, antihistamines, glucocorticoids, and more are discussed in detail, with relevant studies. The article also addresses current challenges and future directions, emphasizing the need for improved nanosuspension stability and exploring potential technologies. Nanosuspensions have shown substantial potential in advancing ophthalmic drug delivery by enhancing solubility and absorption. This article is a valuable resource for researchers, clinicians, and pharmaceutical professionals in this field, offering insights into recent developments, challenges, and future prospects in nanosuspension use for ocular drug delivery.

The nanocrystal (NC) technology has become one of the most commonly used strategies for the formulation of poorly soluble actives. Given their large specific surface, NCs are mainly used to enhance the oral absorption of poorly soluble actives. Differently from conventional nanoparticles, which require the use of carrier materials and have limited drug loadings, NCs\' drug loading approaches 100% since they are formed of the pure drug and surrounded by a thin layer of a stabilizer. In this work, we report the covalent decoration of curcumin NCs with folic acid (FA) using EDC/NHS chemistry and explore the novel systems as highly loaded \"Trojan horses\" to target cancer cells. The decorated NCs demonstrated a remarkable improvement in curcumin uptake, exhibiting enhanced growth inhibition in cancer cells (HeLa and MCF7) while sparing healthy cells (J774A.1). Cellular uptake studies revealed significantly heightened entry of FA-decorated NCs into cancer cells compared to unmodified NCs while also showing reduced uptake by macrophages, indicating a potential for prolonged circulation in vivo. These findings underline the potential of NC highly loaded nanovectors for drug delivery and, in particular, for cancer therapies, effectively targeting folate receptor-overexpressing cells while evading interception by macrophages, thus preserving their viability and offering a promising avenue for precise and effective treatments.

Nanosuspensions (NSps) are colloidal dispersions of particles that have the potential to solve the delivery problems of active ingredients associated with their low solubility in water or instability due to environmental factors. It is essential to consider their chemical composition and preparation methods because they directly influence drug loading, size, morphology, solubility, and stability; these characteristics of nanosuspensions influence the delivery and bioavailability of active ingredients. NSps provides high loading of drugs, protection against degrading agents, rapid dissolution, high particle stability, and high bioavailability of active ingredients across biological membranes. In addition, they provide lower toxicity compared to other nanocarriers, such as liposomes or polymeric nanoparticles, and can modify the pharmacokinetic profiles, thus improving their safety and efficacy. The present review aims to address all aspects related to the composition of NSps, the different methods for their production, and the main factors affecting their stability. Moreover, recent studies are described as carriers of active ingredients and their biological activities.

Oral administration and intramuscular (IM) injection are commonly recommended options for human immunodeficiency virus (HIV) treatment. However, poor patient compliance due to daily oral dosing, pain at injection sites and the demand for trained healthcare staff for injections limit the success of these administration routes, especially in low-resource settings. To overcome these limitations, for the first time, we propose novel bilayer dissolving microneedles (MNs) for the intradermal delivery of long-acting nanosuspensions of the antiretroviral (ARV) drug bictegravir (BIC) for potential HIV treatment and prevention. The BIC nanosuspensions were prepared using a wet media milling technique on a laboratory scale with a particle size of 358.99 ± 18.53 nm. The drug loading of nanosuspension-loaded MNs and BIC powder-loaded MNs were 1.87 mg/0.5 cm2 and 2.16 mg/0.5 cm2, respectively. Both dissolving MNs exhibited favorable mechanical and insertion ability in the human skin simulant Parafilm® M and excised neonatal porcine skin. Importantly, the pharmacokinetic profiles of Sprague Dawley rats demonstrated that dissolving MNs were able to intradermally deliver 31% of drug loading from nanosuspension-loaded MNs in the form of drug depots. After a single application, both coarse BIC and BIC nanosuspensions achieved sustained release, maintaining plasma concentrations above human therapeutic levels (162 ng/mL) in rats for 4 weeks. These minimally invasive and potentially self-administered MNs could improve patient compliance, providing a promising platform for the delivery of nanoformulated ARVs and resulting in prolonged drug release, particularly for patients in low-resource settings.

Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes.

Cinnamomum zeylanicum is a traditional medicinal plant known for its anti-inflammatory, antidiabetic, antimicrobial, anticancer, and antioxidant properties. Its therapeutic efficacy using nanosuspensions is still unclear for treating infectious diseases. This study was designed to evaluate the bioactivities, biochemical characterization, and bioavailability of freshly prepared nanosuspensions of C. zeylanicum. Structural and biochemical characterization of C. zeylanicum and its biological activities, such as antioxidants, antimicrobials, antiglycation, α-amylase inhibition, and cytotoxicity was performed using Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC). C. zeylanicum extract and nanosuspensions showed TPCs values of 341.88 and 39.51 mg GAE/100 g while showing TFCs as 429.19 and 239.26 mg CE/100g, respectively. DPPH inhibition potential of C. zeylanicum extract and nanosuspension was 27.3% and 10.6%, respectively. Biofilm inhibition activity revealed that bark extract and nanosuspension showed excessive growth restraint against Escherichia coli, reaching 67.11% and 66.09%, respectively. The α-amylase inhibition assay of extract and nanosuspension was 39.3% and 6.3%, while the antiglycation activity of nanosuspension and extract was 42.14% and 53.76%, respectively. Extracts and nanosuspensions showed maximum hemolysis at 54.78% and 19.89%, respectively. Results indicated that nanosuspensions possessed antidiabetic, antimicrobial, anticancer, and antioxidant properties. Further study, however, is needed to assess the clinical studies for the therapeutic use of nanosuspensions.

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.