This review explores the enhanced transdermal therapy of several skin disorders with the application of carriers comprising phospholipid vesicular gel systems. Topical drug delivery has several advantages compared to other administration methods, including enhanced patient compliance, the avoidance of the first-pass impact associated with oral administration, and the elimination of the need for repeated doses. Nonetheless, the skin barrier obstructs the penetration of drugs, hence affecting its therapeutic efficacy. Carriers with phospholipid soft vesicles comprise a novel strategy used to augment drug delivery into the skin and boost therapeutic efficacy. These vesicles encompass chemicals that possess the ability to fluidize phospholipid bilayers, producing a pliable vesicle that facilitates penetration into the deeper layers of the skin. Phospholipid-based vesicular carriers have been extensively studied for improved drug delivery through dermal and transdermal pathways. Traditional liposomes are limited to the stratum corneum of the skin and do not penetrate the deeper layers. Ethosomes, glycerosomes, and glycethosomes are nanovesicular systems composed of ethanol, glycerol, or a combination of ethanol and glycerol, respectively. Their composition produce pliable vesicles by fluidizing the phospholipid bilayers, facilitating deeper penetration into the skin. This article examines the impact of ethanol and glycerol on phospholipid vesicles, and outlines their respective manufacturing techniques. Thus far, these discrepancies have not been analyzed comparatively. The review details several active compounds integrated into these nanovesicular gel systems and examined through in vitro, in vivo, or clinical human trials involving compositions with various active molecules for the treatment of various dermatological conditions.

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 3³ Box–Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.

Introduction: Atorvastatin (ATV), a medication used to reduce cholesterol levels, possesses properties that can counteract the damaging effects of free radicals and reduce inflammation. However, the administration of ATV orally is associated with low systemic bioavailability due to its limited capacity to dissolve in water and significant first-pass effect. This study aimed to assess the appropriateness of employing nano-vesicles for transdermal administration of ATV in order to enhance its anti-inflammatory effects. Methods: ATV-loaded transethosomes (ATV-TEs) were optimized using the 3³ Box-Behnken design. The ATV-TEs that were created were evaluated for their vesicle size, encapsulation efficiency (% EE), and percent release of drug. The optimum formulation was integrated into a hydroxypropyl methylcellulose (HPMC) emulsion-based gel (ATV-TEs emulgel) using jojoba oil. ATV-TEs emulgel was examined for its physical characteristics, ex vivo permeability, histological, and anti-inflammatory effect in a rat model of inflamed paw edema. Results: The optimized transethosomes exhibited a vesicle size of 158.00 nm and an encapsulation efficiency of 80.14 ± 1.42%. Furthermore, the use of transethosomal vesicles effectively prolonged the release of ATV for a duration of 24 hours, in contrast to the pure drug suspension. In addition, the transethosomal emulgel loaded with ATV exhibited a 3.8-fold increase in the transdermal flow of ATV, in comparison to the pure drug suspension. ATV-TEs emulgel demonstrated a strong anti-inflammatory impact in the carrageenan-induced paw edema model. Discussion: This was evident from the significant reduction in paw edema, which was equivalent to the effect of the standard anti-inflammatory medicine, Diclofenac sodium. Conclusion: In summary, transethosomes, as a whole, might potentially serve as an effective method for delivering drugs via the skin. This could improve the ability of ATV to reduce inflammation by increasing its absorption through the skin.

Inflammation is a vascular response that occurs when the immune system responds to a range of stimuli including viruses, allergens, damaged cells, and toxic substances. Inflammation is accompanied by redness, heat, swelling, discomfort, and loss of function. Natural products have been shown to have considerable therapeutic benefits, and they are increasingly being regarded as feasible alternatives for clinical preventative, diagnostic, and treatment techniques. Natural products, in contrast to developed medications, not only contain a wide variety of structures, they also display a wide range of biological activities against a variety of disease states and molecular targets. This makes natural products appealing for development in the field of medicine. In spite of the progress that has been made in the application of natural products for clinical reasons, there are still factors that prevent them from reaching their full potential, including poor solubility and stability, as well limited efficacy and bioavailability. In order to address these problems, transdermal nanovesicular gel systems have emerged as a viable way to overcome the hurdles that are encountered in the therapeutic use of natural products. These systems have a number of significant advantages, including the ability to provide sustained and controlled release, a large specific surface area, improved solubility, stability, increased targeting capabilities and therapeutic effectiveness. Further data confirming the efficacy and safety of nanovesicles–gel systems in delivering natural products in preclinical models has been supplied by extensive investigations conducted both in vitro and in vivo. This study provides a summary of previous research as well as the development of novel nanovesicular gel formulations and their application through the skin with a particular emphasis on natural products used for treatment of inflammation.

Background/Objectives: Patients with schizophrenia have significant challenges in adhering to and complying with oral medicines, resulting in adverse consequences such as symptom worsening and psychotic relapse. Methods: This study aimed to develop clove oil-based bilosomes using definitive screening design (DSD) to maximize the anti-schizophrenic action of clozapine and promote its nose-to-brain delivery. The target was to optimize the physicochemical properties of bilosomes and incorporate them into mucoadhesive intranasal in situ gels, searching for augmented ex vivo and in vivo clozapine delivery. Results: The bilosomes’ particle size was decreased by increasing the span, SDC, and clove oil amounts. In addition to using a high lipid amount, the aforementioned components also helped increase the entrapment efficiency values. Increased zeta potential was only observed by increasing surfactant amount and reducing clozapine concentration. After incorporation of optimized liquid clove oil-based bilosomes, which had a spherical nano-sized vesicular shape, into P 407-dependent gels, an HPMC (2% w/w)/P 407 (20% w/w)-containing formulation (G6) was selected as an optimized gel owing to its acceptable gelation time (13.28 s), gel strength (27.72 s), viscosity (12,766.67 cP), and mucoadhesive strength (4273.93 dyne/cm²). The optimized G6 exhibited higher J_ss (50.86 μg/cm²·h⁻¹) through the nasal mucosa compared to the control gel (23.03 μg/cm²·h⁻¹). Compared to the control gel, G6 displayed higher relative bioavailability (491.37%) than a commercial tablet (264.46%). Following ELISA analysis, dopamine and serotonin were significantly reduced, while BDNF was remarkably increased after administration of optimized G6 into schizophrenic rats. Conclusion: Our study indicates the potential of intranasal bilosomal gels in upgrading the anti-schizophrenic and neuroprotective activity of clozapine.

Sulpiride (Sul) is a medication that blocks dopamine D₂ receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box–Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y₁), and in vitro drug release (Y₂) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% v/v. Nevertheless, when the glycerin concentration was raised to 40% v/v, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis.