Search Results (80)

Background/Objectives: Curcumin (CUR) has shown promising potential as a wound-healing agent for diabetic wounds; however, its efficacy is hindered by poor aqueous solubility and limited skin permeability. To overcome these limitations, CUR was loaded into myrrh oil-based nanoemulsions (NEs). Methods: The NEs were optimized using a three-factor two-level D-optimal mixture design, and characterized for droplet size, polydispersity index, and zeta potential. The optimized NE was subjected to various stability testing and incorporated into a gel base containing insulin (INS) to form CUR-INS nanoemulgel (CUR-INS-NEG). The antibacterial efficacy of CUR-INS-NEG was tested against various bacterial strains, while its wound-healing effects were evaluated in a diabetic rat wound model. Results: The surfactant/co-surfactant concentration had a greater influence on the NE properties than the oil and aqueous phase concentrations. The optimal NE had a droplet size of 155.2 ± 0.8 nm, a polydispersity index of 0.28, and a zeta potential of −31.4 ± 0.8 mV. It demonstrated sustained drug release, with further release control upon incorporation into the gel base. CUR-INS-NEG demonstrated higher in vitro antibacterial efficacy compared with blank NEG, CUR gel, and INS gel. It also showed 2- and 4-fold reduction in the MIC against S. aureus and E. coli, respectively, compared with CUR gel. In a diabetic wound model, CUR-INS-NEG outperformed both CUR gel and INS gel by enhancing anti-inflammatory and antioxidant effects, as well as collagen deposition and endothelial cell proliferation. Conclusions: The CUR-INS-NEG emerges as an effective system for diabetic wound management, delivering complementary anti-inflammatory, antioxidant, and tissue-regenerative effects of myrrh oil, CUR, and INS. Full article

Nanoemulgels have emerged as a promising hybrid drug delivery system that integrates the advantages of nanoemulsions and gels, offering enhanced drug penetration, prolonged residence time, and improved patient compliance. This review provides a comprehensive overview of the therapeutic applications of nanoemulgels in wound healing, microbial infections, skin cancer, and various dermatological disorders. The article begins with an overview of skin architecture and its implications for cutaneous drug delivery, followed by a clear distinction between transdermal and topical drug delivery systems. The mechanisms of drug transport into and through the skin are discussed in detail, highlighting the role of nano-sized carriers, particularly nanoemulsions, in overcoming the stratum corneum barrier. Mechanistic insights into nanocarrier-mediated cutaneous drug transport and their versatility as dermal delivery platforms are described. The formulation aspects of nanoemulgels, including their components and both high-energy and low-energy methods for nanoemulsion preparation, are critically discussed to elucidate their impact on formulation performance. An overview of in vitro characterization techniques and biological screening methods employed to evaluate nanoemulgel performance is presented, along with a tabulated compilation of relevant patents to highlight translational progress. Finally, current challenges, regulatory considerations, and future perspectives are discussed, underscoring the potential of nanoemulgels as a versatile and effective platform for advanced topical drug delivery. Full article

Background/Objectives: Nanoemulsions (NEs) are highly promising drug delivery systems that can be made user-friendlier by thickening to nanoemulsion gels (NEGs). However, in order to be regulatory accepted, such a transformation requires systematic understanding of the underlying interactions and stabilization mechanisms, especially when the incorporated active pharmaceutical ingredient may infiltrate the stabilizer layer. Methods: NEs with/without ibuprofen were submitted through direct vs. indirect gelation using three different gelling agents (carbomer 980, xanthan gum, or polyacrylate crosspolymer-6). Multi-technique characterization was employed to demonstrate nanoparticle preservation within the gel networks, a point often neglected when studying nanogels. Results: The nanoemulsion with the most favorable properties (55.07 ± 0.82 nm, PDI 0.075 ± 0.022) was successfully transformed into nanoemulgels with all three gelling agents, both by an indirect and direct approach. The combination of Fourier-transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) revealed complex interactions and electron paramagnetic resonance spectroscopy (EPR)-discerned localization of the small-molecule model drug within the surfactants/co-solvents’ microenvironment, while atomic force microscopy (AFM) successfully visualized nanodroplets, with or without the presence of aggregates originating from the applied gelling agent. Conclusions: A series of complementary techniques confirmed the preservation of nanodroplets after transformation while highlighting the potential of novel polyacrylate crosspolymer-6 to produce robust gel network while effectively increasing zeta potential from −11.07 to −30.5 mV and allowing for satisfactory ibuprofen release from nanoparticles. Full article

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide, with letrozole (LZ) serving as a critical aromatase inhibitor for hormone receptor–positive cases. However, long-term oral administration of LZ is often associated with systemic adverse effects and poor patient compliance. To overcome these limitations, new non-aqueous nanoemulgels (NEMGs) were developed for transdermal delivery of LZ. Methods: The NEMGs were formulated using glyceryl monooleate (GMO), Sepineo P600^®, Transcutol, propylene glycol, and penetration enhancers propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC), and Captex^®. Physicochemical characterization, solubility, stability, and in vitro permeation studies were conducted using Strat-M^® membranes, while in vivo pharmacokinetics were evaluated in rat models. Results: The optimized GMO/PGMC-based NEMG demonstrated significantly enhanced drug flux, higher permeability coefficients, and shorter lag times compared with other NEMGs and suspension emulgels. In vivo, transdermal application of the GMO/PGMC-based NEMG over an area of 2.55 cm² produced dual plasma absorption peaks, with 57% of the LZ dose absorbed relative to oral administration over 12 days. Shelf-life and accelerated stability assessments confirmed excellent physicochemical stability with negligible crystallization. Conclusions: The developed LZ NEMG formulations offer a stable, effective, and patient-friendly transdermal drug delivery platform for breast cancer therapy. This system demonstrates potential to improve patient compliance and reduce systemic toxicity compared to conventional oral administration. Full article

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. Full article

This study reports the development and optimization of a Melissa officinalis oil-based nanoemulgel for transdermal delivery using a Design-of-Experiments (DoE) approach. A Central Composite Design (CCD) was applied to optimize Tween 80 concentration and homogenization time, resulting in a nanoemulsion with a droplet size of 127.31 nm, PDI of 17.7%, and zeta potential of −25.0 mV, indicating good colloidal stability. FTIR analysis confirmed the presence of functional groups such as O–H, C=O, and C–O–C, supporting the oil’s phytochemical richness and therapeutic potential. DSC analysis revealed enhanced thermal stability and successful encapsulation, while SEM imaging showed a uniform and spherical microstructure. The drug release followed Higuchi kinetics (R² = 0.900), indicating diffusion-driven release, with the Korsmeyer–Peppas model (n = 0.88) suggesting anomalous transport. Antibacterial studies showed inhibition of Staphylococcus aureus (MIC = 250 µg/mL) and Escherichia coli (MIC = 500 µg/mL). In vivo anti-inflammatory testing demonstrated significant edema reduction (p < 0.05) using a carrageenan-induced rat paw model. These results support the potential of Melissa nanoemulgel as a stable and effective topical therapeutic for inflammatory and microbial skin disorders. Full article

This study aimed to investigate the production of nanoemulgels structured with flaxseed fiber, designed to simulate salad dressings. For this purpose, the influence of microfluidizer passes (from one to four) on physicochemical and rheological properties was determined, followed by an assessment of thermal behavior. Rotor–stator homogenization followed by microfluidization were employed to produce nanoemulgels, which were characterized using laser diffraction, multiple light scattering, and rheological measurements. The resulting systems exhibited monomodal particle size distributions with mean diameters below 220 nm. Increasing the number of microfluidizer passes from one to four led to slight reductions in particle size, although they were not statistically significant. The formulation with two passes demonstrated superior physical stability during aging studies. Rheological evaluation indicated enhanced gel-like behavior with up to three passes, whereas excessive energy input (four passes) slightly compromised structural integrity. The linear viscoelastic region decreased notably after the first pass but remained relatively stable thereafter. The two-pass nanoemulgel, identified as the optimal formulation, was further tested for thermal stability. Temperature increases (5–20 °C) led to minor decreases in viscosity and firmness, yet the structure remained thermally stable. These findings support microfluidization as an effective strategy for developing stable flaxseed fiber-based nanoemulgels, with potential applications in functional food systems. Full article

This study investigates the Quality by Design (QbD)-driven development and optimization of a nanoemulgel incorporating Kunzea ericoides oil for transdermal therapy. Nanoemulgels enhance percutaneous drug delivery, sustain release profiles, and improve bioavailability. A central composite design was employed to optimize critical formulation parameters, with ANOVA confirming a statistically significant impact on particle size and drug release kinetics (p < 0.05). The optimized formulation exhibited a particle size of 112.38 nm, a polydispersity index of 0.203, and a zeta potential of −29.0 mV, ensuring colloidal stability. In vitro drug release followed the Higuchi model (R² = 0.989, kH = 4.776), indicating diffusion-controlled kinetics, while the Korsmeyer–Peppas model (n = 0.88) suggested an anomalous transport mechanism. Antibacterial studies determined minimum inhibitory concentrations of 250 µg/mL for Staphylococcus aureus and 500 µg/mL for Escherichia coli, indicating greater susceptibility in S. aureus. In vivo anti-inflammatory evaluation using a carrageenan-induced paw edema model demonstrated a statistically significant reduction in inflammation (p = 0.005 at 60 min), with a near-complete resolution by 240 min. These findings underscore the potential of Kunzea ericoides nanoemulgel as a promising transdermal therapeutic, integrating controlled drug release with potent anti-inflammatory and antibacterial properties for dermatological and inflammatory conditions. Full article

Periodontitis is a prevalent oral condition worldwide. Azithromycin, a conventional lipophilic drug for periodontal treatment, often causes systemic side effects when administered orally. To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2–8 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 µg/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment. Full article

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10⁻² cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher C_max (2.13 µg/mL), a prolonged half-life (t_1/2 = 16.12 h), and an increased AUC_0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy. Full article

Background: Acne is a prevalent dermatological condition characterized by the blockage of hair follicles and sebaceous glands, leading to the formation of acne. The anaerobe pathogen Cutibacterium acnes (formerly known as Propionibacterium acnes) plays an essential role in the pathogenesis of acne, for which generally antimicrobial treatment is required. Acne is a substantial health concern, and continuing research is being conducted to discover novel and efficacious remedies. The antimicrobial activity of plants has been demonstrated in numerous studies, and they are still targeted organisms in drug development. Studies showing that plants are effective against acne pathogens have also been reported. Methods: The antimicrobial activity of the hydroethanolic extracts prepared from 30 plant species was determined against C. acnes standard strains (C. acnes Scholz and Kilian ATCC 11827 and ATCC 11828) and 30 clinical isolates in our preliminary screening. Since acne is an inflammatory skin disease, the anti-inflammatory effect of six active extracts against C. acnes was determined through the in vitro inhibition of collagenase, lipoxygenase (LOX), hyaluronidase and xanthine oxidase (XO) enzymes. Results: Cotinus coggygria Scop. leaf extract displayed the highest hyaluronidase and collagenase inhibition (79.75% and 52.52%, respectively), while the extract from the aerial parts of Helichrysum arenarium (L.) Moench demonstrated a potent XO inhibitory effect (82.51%). Therefore, these two extracts have been chosen for further studies, and LC/MS-MS was used to determine the phenolic profiles of these extracts. Conclusions: Subsequently, nanoemulgels were formulated with the active extracts to develop a prototype herbal anti-acne product, and characterization studies of the formulations were conducted. Full article

Aim: To investigate the anti-inflammatory, antioxidant, and diabetic wound healing properties of the novel topical formulation [Ferulic acid-loaded nanoemulgel (DLMGO-G)]. Methods: Ferulic acid nanoemulsion developed with lemongrass oil is investigated in diabetic wound healing. Further nanoemulsion is incorporated into 1% carbopol^® 934 to obtain the DLMGO-G. Nanoemulsion was characterized for particle size, and polydispersity index (PDI) was obtained by Malvern Zetasizer (Zetasizer Nano ZS, Malvern, AL, USA), and morphology by TEM (JEM 1400, JOEL, Akishima, Japan). Furthermore, in vitro cell line and in vivo studies were carried out. Results: The developed nanoemulsion showed a globule size of 28.04 ± 0.23 nm and PDI of 0.07 ± 0.01. The morphology of nanoformulations by TEM confirmed the spherical and uniform nature. Further, the nanoformulation in in vitro cell line experiments revealed that the IC50 value was increased by 1.52 times compared to the drug solution. The treatment groups have shown that fibroblast morphologies were spindle-shaped, suggesting that nanoformulation was compatible with the cells and developed normally on nanoformulation. It also reduced ROS with improved internalization more than the control group. The in vitro wound healing model also revealed that nanoformulation had better wound healing activity. In the in vivo diabetic wound studies on male SD rats, the levels of inflammatory markers such as TNF-α, IL-6, IL-22, and IL-1β declined significantly when treated with DLMGO-G. IL-10 levels significantly increased compared to the diseased group, and MMP-9 levels were remarkably decreased compared to the diseased group. Furthermore, histopathological studies showed the regeneration and granulation of tissues. Conclusions: Thus, these findings indicate that FA-loaded nanoemulgel greatly accelerates the healing of wounds in diabetic rats. Full article