Nanoemulsions (NEs) are submicron-sized heterogeneous biphasic liquid systems stabilized by surfactants. They are physically transparent or translucent, optically isotropic, and kinetically stable, with droplet sizes ranging from 20 to 500 nm. Their unique properties, such as high surface area, small droplet size, enhanced bioavailability, excellent physical stability, and rapid digestibility, make them ideal for encapsulating various active substances. This review focuses on recent advancements, future prospects, and challenges in the field of NEs, particularly in oral, parenteral, and ophthalmic delivery. It also discusses recent clinical trials and patents. Different types of in vitro and in vivo NE characterization techniques are summarized. High-energy and low-energy preparation methods are briefly described with diagrams. Formulation considerations and commonly used excipients for oral, ocular, and ophthalmic drug delivery are presented. The review emphasizes the need for new functional excipients to improve the permeation of large molecular weight unstable proteins, oligonucleotides, and hydrophilic drugs to advance drug delivery rapidly.

Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Curcuma longa Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin’s beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.

Nanosuspensions (NS), with their submicron particle sizes and unique physicochemical properties, provide a versatile solution for enhancing the administration of medications that are not highly soluble in water or lipids. This review highlights recent advancements, future prospects, and challenges in NS-based drug delivery, particularly for oral, ocular, transdermal, pulmonary, and parenteral routes. The conversion of oral NS into powders, pellets, granules, tablets, and capsules, and their incorporation into film dosage forms to address stability concerns is thoroughly reviewed. This article summarizes key stabilizers, polymers, surfactants, and excipients used in NS formulations, along with ongoing clinical trials and recent patents. Furthermore, a comprehensive analysis of various methods for NS preparation is provided. This article also explores various in vitro and in vivo characterization techniques, as well as scale-down technologies and bottom-up methods for NS preparation. Selected examples of commercial NS drug products are discussed. Rapid advances in the field of NS could resolve issues related to permeability-limited absorption and hepatic first-pass metabolism, offering promise for medications based on proteins and peptides. The evolution of novel stabilizers is essential to overcome the current limitations in NS formulations, enhancing their stability, bioavailability, targeting ability, and safety profile, which ultimately accelerates their clinical application and commercialization.

Natural substances, especially those derived from plants, exhibit a diverse range of therapeutic benefits, such as antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. Nevertheless, their use in clinical settings is frequently impeded by inadequate solubility, limited bioavailability, and instability. Nanovesicular carriers, such as liposomes, niosomes, ethosomes, transferosomes, transethosomes, and cubosomes, have emerged as innovative phytochemical delivery systems to address these limitations. This review highlights recent developments in vesicular nanocarriers for phytochemical delivery, emphasizing preparation techniques, composition, therapeutic applications, and the future potential of these systems. Phytosomes, along with their key advantages and various preparation techniques, are extensively described. Various in vitro and in vivo characterization techniques utilized for evaluating these nanovesicular carriers are summarized. Completed clinical trials and patents granted for nanovesicles encapsulating phytochemicals designed for systemic delivery are tabulated. Phytochemical delivery via vesicular carriers faces challenges such as low stability, limited active loading, scalability issues, and high production costs. Additionally, immune clearance and regulatory hurdles hinder clinical application, requiring improved carrier design and formulation techniques.

Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort.