Spontaneous Emulsification Research Articles

Self-nanoemulsifying drug delivery system for nebulization: fabrication and evaluation for systemic delivery of atorvastatin.

The study undertakes the development of an atorvastatin-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve its bioavailability. The SNEDDS were fabricated using oleic acid, Tween 80, and Span 80 by spontaneous emulsification. The SNEDDS were assessed for their particle size distribution, zeta potential, morphology, drug content, surface tension, viscosity, and drug release. The aerodynamic performance of the SNEDDS was evaluated using an Andersen cascade impactor, while the lipid-lowering potential of the SNEDDS was determined in Wistar rats using the analyzer "Microlab 300." The particle size of the SNEDDS ranged from 36 to 311nm, with a polydispersity index (PDI) of 0.25-0.40. The zeta potential of the SNEDDS fluctuated from - 29.22 to - 38.26mV, which declined to - 4.55mV in the case of F5. The chitosan-coated formulation (F5) exhibited a higher viscosity (22.12mPas) and lower surface tension (0.056 dyne/cm) than other formulations (F1-F4). The non-coated formulation exhibited a significantly higher burst drug release, followed by a sustained drug release pattern (p ≤ 0.05) as compared to the coated formulation (F5). The nebulized SNEDDS achieved a dispersed fraction of 87 to 97%, where notably higher aerosol dispersion from F4 was attributed to its smaller particle size and circularity. The inhaled fraction of nebulized SNEDDS was 74-87%. The size of the SNEDDS droplets was the primary determinant affecting the aerodynamic performance of the SNEDDS during nebulization. The chitosan-coated SNEDDS achieved a higher antihyperlipidemic effect than marketed tablets, which shows the suitability of F5 for effective systemic delivery of atorvastatin through the lung.

Evaluation of citronella oil nanoemulsion formulation against the insect-stored pest Callosobruchus maculatus (Fab.) (Coleoptera: Bruchidae)

Citronella (Cymbopogon nardus) produces essential oil and has the potential to be developed as a botanical insecticide. However, in its development, botanical insecticides encountered several obstacles. Utilizing nanotechnology in nanoemulsion preparations is one method to overcome these challenges. This research aimed to determine the contents of the citronella oil nanoemulsion (CiONano) and citronella oil non-nano emulsion (CiONonNano) formulations and evaluate the toxicity, repellency, and prevention of oviposition against female adults of Callosobruchus maculatus. This was the first work to evaluate the nanoemulsion of citronella oil prepared from spontaneous emulsification against C. maculatus. Chemical content testing used the GCMS method. A toxicity test using the contact method (LC50), used a probit program, while testing for repellency and oviposition deterrence was carried out using the no-choice method. The highest chemical component of CiONonNano and CiONano was citronella (37.56 and 38.97%, respectively), followed by citronellol (17.71 and 18.99%, consecutively) and geraniol (14.78 and 15.38%, respectively). In general, the CiONano formulation showed higher repellency and toxicity than CiONonNano. The LC50 values of CiONano were 10.03%. These values were 4.49 times lower than the LC50 of CiONonNano. However, the results of the oviposition inhibition test showed different results, the CiONonNano formulation had a higher oviposition inhibition capacity for adult female C. maculatus than CiONano. As a result, it is necessary to optimize the CiONano formulation to obtain consistent results in controlling C. maculatus.

Formulation and characterization of nanoemulsion biopesticide from Balanite aegyptiaca seed kernel extract

Consumers’ growing awareness and desire for food free of pesticide residues led to the incubation of this research work. The study aimed at developing a nanoemulsion formulation of Balanite aegyptiaca seed kernel extract for use as a biopesticide. A preliminary study was carried out on the solubility and miscibility of surfactant, carrier, and deionized water utilizing the low-energy spontaneous emulsification method. Information from the study was then used to plot a ternary phase diagram (TPD) showing both the isotropic zone and the anisotropic zones, from which a point with a surfactant, oil, and water ratio (20:20:60) was selected from the isotropic zone for the formulation. The developed nanoemulsion was tested for stability and thermostability, and both results revealed the system was stable. Similarly, the physiochemical properties of the developed nanoemulsion system were characterized, and the results showed that the system revealed the following properties: mean particle size of 173.2±21.6, polydispersity index (PDI) of 0.403±0.038, surface tension of 32.53±0.71, viscosity of 37.33±0.67 mPas, and a pH of 4.92±0.02. The formulation appears homogeneous, clear, and transparent, which further indicates it’s a nanoemulsion formulation. Therefore, the nanoemulsion formulation of B. aegyptiaca seed kernel can serve as a safe and environmentally friendly substitute for synthetic pesticides in the management of plant diseases.

Renewable oleyl based surfactants for application in liquid explosive high internal phase emulsions

A series of sustainable surfactants derived from oleic acid have been synthesized and tested for their ability to form high internal phase emulsions (HIPEs) for liquid explosives. Two surfactants have been highlighted for their ability to form stable ‘double salt’ (ammonium and calcium nitrate) emulsions. These stabilizers can be prepared at kilogram scale in either one or two steps from commercially available, sustainable methyl oleate and crucially can be used directly in HIPE formulation without the need for further purification. Pendant drop tensiometry studies of purified material however indicate potential for other applications such as enhanced oil recovery and their ability to form spontaneous emulsions.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Spontaneous Emulsification of Organometallic Complexes Applied to the Synthesis of Nanocapsules Active for H2 Release from Ammonia-Borane.

Herein, we achieved spontaneous emulsification of organometallic precursors to elaborate subμm metal nanocapsules after interfacial reduction. Depending on the proportion of the three components, water, solvent, and the metal precursor, either thermodynamically stable "surfactant-free microemulsions" (SFME) or metastable Ouzo emulsions are formed. We investigated the catalytic transition metals Au, Pd, and Pt, individually or combined, and stabilized by various ligands. Upon reduction of the precursors, either shells of discrete nanoparticles (NPs) or continuous shells were obtained, for the SFME and Ouzo emulsions, respectively. The Au/Pd mixed emulsions lead to a unique structural morphology, in which the Au-Pd nanoparticles are embedded in a continuous submicronic metal shell. The AuNPs are available to grow larger particles within the NP shell using a seeded growth approach. The water-stable and surfactant-free nanocapsules are appealing as catalysts, and, as such, were evaluated for the hydrolysis of ammonia-borane as a promising catalytic strategy for H2 release from an H-high-content storage material. This work establishes for the first time a genuine activity of water-compatible gold colloids for this reaction.

Unraveling Early-Stage Dynamics of Cage-to-Covalent Organic Framework Transformation at Liquid-Liquid Interface.

Postsynthetic linker exchange (PLE) has emerged as an emerging synthetic strategy for constructing high-quality covalent organic frameworks (COFs) from preassembled entities such as linear polymers, amorphous networks, COFs, and porous organic cages by using the principles of dynamic covalent chemistry. The PLE strategy has recently been extended at the liquid-liquid interface to fabricate highly crystalline two-dimensional (2D)-COF membranes at a faster time scale (24 h). Examining the early stages of the interfacial PLE dynamics becomes essential to understanding the expedited COF growth process. In this regard, pendant drop tensiometry has been employed to probe the initial reaction dynamics of the imine cage-to-COF transformation through dynamic interfacial tension (IFT) measurements. The contrasting trends in IFT profiles between PLE-mediated (from cage) and direct COF synthesis (from parent monomers) are in qualitative agreement with the kinetics of bulk-scale interfacial polymerizations. Further, the distinct early-stage interfacial behaviors between the diverse synthetic routes have been experimentally demonstrated using tensiometry, optical microscopy, electron microscopy, and powder X-ray diffraction (PXRD) analysis. The pivotal role of in situ generated imine intermediates (ImIs) and the phenomenon of spontaneous emulsification toward accelerated interfacial COF growth process was delineated. The current study on deploying the pendant drop tensiometric technique to examine early-stage interfacial polymerization dynamics opens up a gripping avenue for mechanistic exploration in PLE-based COF synthesis. The generality of the developed methodology to study the initial COF growth kinetics was extended to a new interfacial PLE-mediated cage-to-COF transformation.

Factors, Mechanisms, and Kinetics of Spontaneous Emulsification for Heavy Oil-in-Water Emulsions.

In challenging reservoirs where thermal recovery falls short, cold or chemical oil recovery methods are crucial. Spontaneous emulsification (SE), triggered by gentle disturbance, significantly enhances oil recovery. In elucidating SE mechanisms and kinetics, SE processes via direct contact between oil and aqueous phases without stirring were conducted. The effects of temperature, emulsifier concentration, pH, NaCl concentration, and the oil-to-water ratio on SE were investigated through droplet size analysis and turbidity measurements. Furthermore, the emulsification mechanism and derived emulsification kinetics based on turbidity data were obtained. The results underscore the feasibility of SE for oil-water systems, reducing viscous and capillary resistances without agitation. The emulsified oil mass increased with the temperature, pH, and aqueous-to-oil phase volume ratio while decreasing with the NaCl concentration. In this study, for GD-2 crude oil, the optimal emulsified oil amount occurred at a betaine surfactant (BetS-2) emulsifier concentration of 0.45%. Microscopic photo analysis indicated narrow particle size distributions and small droplets, which remained stable over time under various experimental conditions. A combined SE mechanism involving ultralow interfacial tension, interfacial turbulence due to Marangoni effects, and "diffusion and stranding" due to in situ emulsifier hydrophilicity, was speculated. Additionally, an analogous second-order kinetic equation for SE was proposed, indicating exceptional correlation with calculated and experimentally measured values. This study offers theoretical insight for enhancing oil recovery in chemical and cold production of heavy oil in oilfields.

Therapeutic potential of limonene-based syringic acid nanoemulsion: Enhanced ex-vivo cutaneous deposition and clinical anti-psoriatic efficacy

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of −21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

Integrating phase change materials and spontaneous emulsification: In-situ particle formation at oil–water interfaces

The properties of interfaces between two immiscible fluids, as engineered by interfacial materials, are crucial in various processes, including printing, coating, and multiphase flow in porous media. Interfacial materials, such as surface-active molecules and particles can be adsorbed from the bulk fluid phases to the interface or formed in-situ at the interface. In this study, we develop a methodology to form stiff silica-based particles in situ at the oil–water interface through coupling of phase change materials and spontaneous emulsification. This process is demonstrated by introducing a heptane micellar solution that spontaneously generates a microemulsion phase when in contact with an aqueous phase. Micron-sized droplets, consisting of an aqueous silicate precursor mixture, undergo a sol–gel reaction, leading to the generation of colloidal-sized particles. SEM micrographs and confocal images of dried samples, taken from the aqueous-heptane interface, reveal the formation of particles post-gelation. The in-situ formation of stiff particles can be characterized through the dynamics of evaporation, where a significant reduction in the heptane evaporation rate is observed. This particle generation method, utilizing phase change materials and emulsion templates, is spontaneous, energy-efficient, and enables particle formation at the interface at a predetermined time. Our findings offer valuable insights for the fabrication of interfacial materials with tailored properties and controlled timing.

Novel Hydrogels Based on the Nano-Emulsion Formulation Process: Development, Rheological Characterization, and Study as a Drug Delivery System.

In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the physicochemical behavior and interactions between nonionic surfactants and oil and water phases, according to a process close to spontaneous emulsification used in the production of nano-emulsions. Contrary to the classical process of emulsion-based gel formulation, we propose a simple one-step approach. Beyond the originality of the concept, these nanoemulgels appear as very promising systems able to encapsulate and deliver various molecules with different solubilities. In the first section, we propose a comprehensive investigation of the gel formation process and its limits through oscillatory rheological characterization, characterization of the sol/gel transitions, and gel strength. The second section is focused on the follow-up of the release of an encapsulated model hydrophilic molecule and on the impact of the rheological gel properties on the release profiles.

Revealing the Existence of Long-Range Liquid-Liquid Interfacial Potential in Phase-Transfer Processes.

By employing fluorescence wide-field microscopy and a nanoparticle-based phase transfer catalyst (PTC), consisting of a fluorescent silica nanoparticle functionalized with trioctylpropylammonium bromide, we demonstrate that in the presence of NaOH, single nanoparticles display subdiffusive motion along the axis normal to an aqueous liquid-organic liquid interface. This is because of an extended interfacial potential with a shallow well (∼1 kBT) that stretches a few μm into the organic phase, in contrast to previous molecular dynamics studies that reported narrow interfaces on the order of ∼1 nm. Spontaneous interfacial emulsification induced by NaOH results in the propagation of water-in-oil nanoemulsions into the organic solvent that creates an equilibrium hybrid-solvent composition that solvates the PTC. A greater mobility and longer residence time of the PTC at the potential well enhance the interfacial phase transfer process and catalytic efficiency.

Proper Determination of Phase Diagrams while Nanoprecipitating Oils.

The Ouzo effect is a generic process to generate colloidal dispersions from a variety of solutes. Whereas phase diagrams have been quite easily established when nanoprecipitating polymers, the case of oils is less straightforward. Indeed, the short-term stability of generated nanodroplets in water/solvent mixtures complexifies the identification of the diagram boundaries. This article proposes two complementary methods, namely, fluorescence microscopy and dynamic light scattering, to determine with fair accuracy Ouzo limits in ternary systems oil/solvent/nonsolvent, without and with a surfactant, respectively. This accuracy in PD determination opens the way to a better understanding and control of the aggregation events during the nanoprecipitation process.

Effect of gelling agents on properties of coumestrol-loaded nanoemulsions – Formulation, skin retention/permeation, antioxidant and skin photoprotective activities

Coumestrol is an isoflavonoid that exhibits antioxidant activity. In this study, hydrogels containing coumestrol-loaded nanoemulsions were designed to protect the skin against UVA/UVB light. The systems investigated were coumestrol-loaded nanoemulsions obtained by spontaneous emulsification procedure formulated in semisolid hydrogels composed of ionic (Carbopol 940®), cationic (chitosan) or non-ionic (hydroxyethylcellulose) gelling materials. Transmission electron microscopy images of formulations showed oil droplets exhibiting 200–300 nm. Hydrogels displayed non-Newtonian shear-thinning behavior. Coumestrol content in formulations remained close to 100 % (1 mg/mL) over time (up to 90 days). Regardless of the gelling material used, a lowering of coumestrol release rate was observed, in comparison with the release from nanoemulsion. The permeation and retention of coumestrol in porcine ear skin was evaluated using Franz-type diffusion cells. A higher retention of coumestrol in the epidermis was noticed (20 μg/g) from Carbopol 940-based formulation after 8 h of kinetics. No histological evidence of tissue damage was observed. The nanoemulsion containing coumestrol thickened with Carbopol 940® was selected for further studies. The formulation exhibited antioxidant potential as estimated by TRAP and TAR assays. The skin photoprotective effect was evidenced by means of TBARS, protein carbonylation, and protein thiol content experiments. Overall, our research suggests that the formulation is promising to protect skin against oxidative damage from UVA/UVB light.

Fabrication and characterization of transdermal delivery of ribociclib nanoemulgel in breast cancer treatment

The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO.

Antimicrobial and antioxidant competence of sustainable grumixama leaves extracts in nanoemulsion system

The spontaneous emulsification method was used to produce nanoemulsions loaded with grumixama leaves extracts (GLE) to protect and improve its functionality as a natural additive in food. Nanoemulsions were characterized for physicochemical stability, morphology, thermal analyses, antioxidant capacity, and antimicrobial activity. The formulations showed encapsulation efficiency (EE%) >89%, sizes between 182 and 290 nm, low polydispersity, and zeta potential near −30 mV. The formulations were kinetically stable since these parameters remained constant for up to 180 days at 4°C. The nanoemulsion with 125 mg GLE exhibited better droplet structure, which favored greater phenolic compounds protection and thermal resistance. The antioxidant capacity of all formulations remained stable over 30 days. The nanoemulsions acted as a bactericidal agent (MBC/MIC ratio ≤ 4) against Staphylococcus aureus, Bacillus cereus, and Listeria monocytogenes strains. However, GLE-loaded nanoemulsions offer a sustainable and functional alternative for use as a natural additive to meet trends such as a clean label.

Continuous synthesis of drug particles via spray drying of emulsions obtained by mechanical emulsification and ouzo effect

In the pharmaceutical field, nanoparticle formulation is an effective approach to improve the solubility of poorly water-soluble drugs. Spray drying is used for the synthesis of fine drug particles. The particle size obtained by spray drying generally depends on the size of the sprayed droplet. In this study, an emulsion spray drying method is proposed as a novel method for nanoparticle synthesis. Oil-in-water (O/W) nanoemulsions containing oil-soluble drugs were prepared. Spraying O/W emulsions could produce fine particles with the size of 122 nm. The particles obtained by emulsion spray drying were smaller than those obtained by spray drying without an emulsion. Furthermore, an Ouzo emulsion, which is a self-emulsification method, was investigated to improve the particle yield. The particles obtained by spray drying of the Ouzo emulsion had the size of 0.50 μm, which was smaller than those obtained without the Ouzo emulsion. Moreover, in-vitro dissolution tests were performed to evaluate the solubility of the obtained particles as well as the unprocessed drug powder. The particles obtained via spray drying of the Ouzo emulsions showed the highest dissolution rate. In summary, spray drying of O/W and Ouzo emulsions resulted in the production of fine drug particles.

Hesperidin nanoparticles for prostate cancer therapy: preparation, characterization and cytotoxic activity

Hesperidin, a phytochemical renowned for its therapeutic effects including anticancer, antioxidant, and anti-inflammatory properties, encounters a significant limitation in its application due to its low bioavailability and restricted solubility in water. To surmount these challenges, we employed a spontaneous emulsification method to produce hesperidin nanoparticles. These nanoparticles, averaging 197.2 ± 2.8 nm, exhibited uniform dispersion (polydispersity index: 0.13), a zeta potential (ZP) of −28 mV, encapsulation efficiency of 84.04 ± 1.3%, and demonstrated stable and controlled release across various environments. Assessment of the nanoemulsions stability revealed remarkably high stability levels. Cytotoxicity evaluations (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-2-H-tetrazolium bromide, neutral red, trypan blue, and lactate dehydrogenase) indicated that cancer cell viability following treatment with hesperidin nanoemulsion was concentration and time-dependent, significantly lower compared to cells treated with free hesperidin. The colony formation assay and cell morphology evaluation further corroborated the heightened efficacy of hesperidin in its nano form compared to the free form. In summary, hesperidin nanoparticles not only exhibited more potent anticancer activity than free hesperidin but also demonstrated high biocompatibility with minimal cytotoxic effects on healthy cells. These findings underscore the potential for further exploration of hesperidin nanoparticles as an adjunctive therapy in prostate cancer therapy.

Linezolid Loaded Nanoparticle for Topical Administration of Diabetic Foot Treatment: Formulation, In Vitro and Ex Vivo Characterization

The aim of this research work was to develop a topical gel formulation containing nanoparticle to diabetic foot ulcer (DFU). In this respect, the nanoparticle formulations were prepared by using spontaneous emulsification technique. The linezolid (LZD) loaded nanoparticle formulation exhibited an low average particle size (PS) of 195.27±5.42 nm, low polydispersity index (PI) of 0.214±0.019, a high zeta potential (ZP) of 20.57±0.35 and high drug entrapment efficiency (EE) of 99.746±0.021%. In order to enhance topical residence time, the LZD-loaded nanoparticles were dispersed in a gel formulation using Methocel TM K4M (HPMC) and Carbopol® 974 P NF. The formulated gels demonstrated favorable characteristics, including an appropriate pH value, suitable mechanical performance, and desirable viscosity and spreadability for topical administration. All formulations displayed pseudoplastic flow and exhibited typical gel-type mechanical spectra at the specified frequency value. Moreover, the developed formulation achieved sustained drug release as intended for these systems. During the ex vivo drug diffusion studies, 0.007±0.004% of LZD was found in receptor phase, and this was an indicator of local effect. The optimum formulation was stable for 6 months. The initial findings suggest that the formulated topical gel containing LZD-loaded nanoparticles holds promise as an effective drug delivery system for DFU management. However, further comprehensive investigations are required to substantiate this hypothesis.

Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.