Retinyl palmitate is a vitamin A ester belonging to the family of endogenous natural retinoid and used to treat various skin disorders like acne, skin aging, wrinkles, and dark spots, as well as to protect against psoriasis. Despite the known therapeutic benefits of retinyl palmitate, the conventional topical delivery of retinyl palmitate commonly associated with adverse reactions such as skin irritation, redness, excessive peeling, and dryness. Therefore, the current study aims to encapsulate the retinyl palmitate in nanoemulsion then incorporate it into a hydrogel system to improve the topical delivery and stability. Low-energy emulsification method was used for the nano-encapsulation of retinyl palmitate. The phase behavior study was used for the investigation and the optimization of the formulation. The droplet size of the optimized nanoemulsion was in nano dimension (16.71 nm) with low polydispersity index (PdI) (0.015), negative zeta potential (−20.6 mV). It demonstrated the influence of vortexing on droplet size and PdI during nanoemulsion preparation. The retinyl palmitate loaded nanoemulgel delivery system exhibited significant improvement (p < 0.05) in skin permeability after topical application. Employment of the nano-encapsulation approach afterward dispersion into hydrogel system for the development of a topical delivery system of retinyl palmitate resulted in improvement in its UV and storage stability as well.

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. In the present study, we investigate the influence of intricate factors including composition and preparation conditions that affect characteristic parameters and the stability of the nanoemulsion formation prepared by the spontaneous emulsification method. Octanoic acid, capryol 90, and ethyl oleate were selected to represent oil phases of different carbon–chain lengths. We explored the impact of the addition mode of the oil–S_mix phase and aqueous phase, vortexing time, K_m (surfactant/cosurfactant) ratio, and the replacement of water by buffers of different pH as an aqueous system. The phase behavior study showed that the S_mix phase had a significant impact on the nanoemulsifying ability of the nanoemulsions composed of oil phases of varying carbon-chain lengths. The mode of mixing of the oil–S_mix phase to the aqueous phase markedly influenced the mean droplet size and size distribution of the nanoemulsions composed of oil phases as capryol 90. Vortexing time also impacted the mean droplet size and the stability of the generated nanoemulsion system depending on the varying carbon-chain length of the oil phase. The replacement of the water phase by aqueous buffers of pH 1.2, 5.5, 6.8, and 7.4 has altered the mean droplet size and size distribution of the nanoemulsion system. Further, the K_m ratio also had a significant influence on the formation of the nanoemulsion system. The findings of this investigation are useful in understanding how the formulation composition and process parameters of the spontaneous emulsification technique are responsible for affecting the physicochemical characteristics and stability of the nanoemulsion system composed of oil of varying carbon-chain (C₈-C₁₈) length.

The current investigation aimed to improve the topical efficacy of imiquimod in combination with curcumin using the nanoemulsion-based delivery system through a combinatorial approach. Co-delivery of curcumin acts as an adjuvant therapeutic and to minimize the adverse skin reactions that are frequently associated with the topical therapy of imiquimod for the treatment of cutaneous infections and basal cell carcinomas. The low-energy emulsification method was used for the nano-encapsulation of imiquimod and curcumin in the nanodroplet oil phase, which was stabilized using Tween 20 in an aqueous dispersion system. The weak base property of imiquimod helped to increase its solubility in oleic acid compared with ethyl oleate, which indicates that fatty acids should be preferred as the oil phase for the design of imiquimod-loaded topical nanoemulsion compared with fatty acid esters. The phase diagram method was used to optimize the percentage composition of the nanoemulsion formulation. The mean droplet size of the optimized nanoemulsion was 76.93 nm, with a polydispersity index (PdI) value of 0.121 and zeta potential value of −20.5 mV. The optimized imiquimod-loaded nanoemulsion was uniformly dispersed in carbopol 934 hydrogel to develop into a nanoemulgel delivery system. The imiquimod nanoemulgel exhibited significant improvement (p < 0.05) in skin permeability and deposition profile after topical application. The in vivo effectiveness of the combination of imiquimod and curcumin nanoemulgel was compared to the imiquimod nanoemulgel and imiquimod gel formulation through topical application for ten days in BALB/c mice. The combination of curcumin with imiquimod in the nanoemulgel system prevented the appearance of psoriasis-like symptoms compared with the imiquimod nanoemulgel and imiquimod gel formulation entirely. Further, the imiquimod nanoemulgel as a mono-preparation slowed and reduced the psoriasis-like skin reaction when compared with the conventional imiquimod gel, and that was contributed to by the control release property of the nano-encapsulation approach.

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to <100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol^® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin.

The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. A self-nanoemulsifying tablet formulation of dapagliflozin propanediol monohydrate was developed utilizing the semisolid pressure-assisted microsyringe (PAM) extrusion-based 3D printing technique. The developed formulation system consists of two major components (liquid and solid phase), which include oils (caproyl 90, octanoic acid) and co-surfactant (PEG 400) as liquid phase while surfactant (poloxamer 188) and solid matrix (PEG 6000) as solid-phase excipients that ultimately self-nanoemulsify as a drug encapsulated nanoemulsion system on contact with aqueous phase/gastrointestinal fluid. The droplet size distribution of the generated nanoemulsion from a self-nanoemulsifying 3D printed tablet was observed to be 104.7 ± 3.36 nm with polydispersity index 0.063 ± 0.024. The FT-IR analysis of the printed tablet revealed that no drug-excipients interactions were observed. The DSC and X-RD analysis of the printed tablet revealed that the loaded drug is molecularly dispersed in the crystal lattice of the tablet solid matrix and remains solubilized in the liquid phase of the printed tablet. SEM image of the drug-loaded self-nanoemulsifying tablets revealed that dapagliflozin propanediol monohydrate was completely encapsulated in the solid matrix of the printed tablet, which was further confirmed by SEM-EDS analysis. The in vitro dissolution profile of dapagliflozin-loaded self-nanoemulsifying tablet revealed an immediate-release drug profile for all three sizes (8 mm, 10 mm, and 12 mm) tablets, exhibiting >75.0% drug release within 20 min. Thus, this study has emphasized the capability of the PAM-based 3D printing technique to print a self-nanoemulsifying tablet dosage form with an immediate-release drug profile for poorly water-soluble drug.