Development of Glycerosomal pH Triggered In Situ Gelling System to Ameliorate the Nasal Delivery of Sulpiride for Pediatric Psychosis.

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.

A Comprehensive Review on Polyphenols Based Nanovesicular System for Topical Delivery.

BACKGROUND: Polyphenols are naturally occurring compounds having more than one hydroxy functional group. They are ubiquitous secondary plant metabolites possessing a wide range of pharmacological activity. Brightly colored fruits and vegetables are the natural source of polyphenols. Majorly, they possess antioxidant, anti-inflammatory and antimicrobial properties which make them suitable candidates to target skin related disorders. OBJECTIVE: This study is focused to explore the potential of polyphenols loaded nanovesicles for skin related disorders. The aim of the study is to review the applicability and efficacy of different vesicular systems encapsulated with various classes of polyphenols for skin related disorders, thus opening the opportunity for future studies based on these drug delivery systems. METHOD: Web of Science, PubMed, Scopus database, and the search engine Google Scholar were accessed for the literature search. The results were then filtered based on the titles, abstracts, and accessibility of the complete texts. RESULTS: The expository evaluation of the literature revealed that various nanovesicles like liposomes, niosomes, ethosomes and transferosomes incorporating polyphenol have been formulated to address issues pertaining to delivery across the skin. These developed nano vesicular systems have shown improvement in the physicochemical properties and pharmacological action. CONCLUSION: Polyphenol based nano-vesicular formulations have proved to be an effective system for topical delivery and henceforth, they might curtail the use of other skin therapies having limited applicability.

Glycerosomes: Novel Nano-Vesicles for Efficient Delivery of Therapeutics.

BACKGROUND: The topical drug delivery system has gained more attention in recent years as compared to oral and parenteral drug delivery. However, owing to the barrier function of the skin's topmost layer, only a few drug molecules can be administered by this route. Therefore, encapsulating the drugs in glycerosomes is one potential solution to this problem. Glycerosomes are vesicular drug delivery systems primarily made up of large concentrations of glycerol, phospholipid, water, and other active ingredients. OBJECTIVE: The main aim of this review is to summarize the most recent information on the encapsulated vesicular system used in cosmetic preparations, specifically glycerosomes made from both synthetic and naturally occurring plant bioactive substances. PURPOSE: Glycerosomes offer many benefits, including increased efficacy, better stability, improve absorption, drug targeting at specific sites, and delivering the same at a predetermined rate. METHOD: The mechanism behind the penetration of glycerosomes is the hydration and lipid fluidization of skin, fabricated by glycerol. RESULT: Numerous methods have been reported for the formulation of glycerosomes, including the thin film hydration method, reverse-phase evaporation, solvent spherule, detergent removal method, and so on. CONCLUSION: Researchers are currently investigating the potential of glycerosomes as nanocarriers for natural bioactive and synthetic drugs. This review describes the structure of glycerosomes, preparation techniques, applications, distinctions from liposomes, and benefits of glycerosomes.

Enhancement of the anti-microbial activity of Mentha spicata essential oil on storage by glycerosomes.

Mentha spicata essential oil (EO) is isolated from the aerial parts of Mentha spicata L. with pronounced antibacterial effects as food preservative in food industry. Nevertheless, its application in the clinical industry and food is significantly restricted by its poor water solubility and physicochemical instability. Glycerosomes of this EO were prepared to enhance its anti-microbial stability. The EO was encapsulated in the glycerosomes and characterized for its physical properties. The optimized EO-loaded glycerosomes displayed entrapment efficiency of 93.2 ± 7.5%, release efficiency of 75.4 ± 6.1%, the particle size of 276 nm, and zeta potential of - 30.4 mV. Scanning electron microscopy (SEM) image showed spherical morphology of the glycerosomes. EO release from optimized formulation of glycerosomes best fitted with a first-order kinetic model. Compared with free EO, EO-loaded glycerosomes showed better storage stability. The results indicated that the incorporation of EO in glycerosomes possessed sustained release properties and significantly enhanced antibacterial effects in storage.

Synergistic approach for acne vulgaris treatment using glycerosomes loaded with lincomycin and lauric acid: Formulation, in silico, in vitro, LC-MS/MS skin deposition assay and in vivo evaluation.

This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of -30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.

A Discursive Review of Recent Development and Patents on Glycerosomes.

BACKGROUND: To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect. OBJECTIVE: The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery. CONCLUSION: Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.

New Vehiculation Systems of Mometasone Furoate for the Treatment of Inflammatory Skin Diseases.

A pre-formulation study was carried out to obtain liposomal formulations of mometasone furoate as an alternative system to marketed forms of corticosteroid for the treatment of inflammatory skin lesions. Mometasone furoate was loaded in glycerosomes and glyceroethosomes, which were also modified with hyaluronic acid (glyceroethohyalurosomes). Vesicles were designed, elaborated, and characterized, and their biocompatibility, efficacy against oxidative stress and skin lesions were assessed in vitro, in human epidermal cells, and in vivo, in a mouse skin epidermal hyperplasia model. All formulations tested showed great encapsulation efficiency, nanometric size, formed monodispersed systems and a highly negative Z potential. Similar values were obtained over nine months storage at 4 °C, which indicates the great stability of the three types of nanoliposomes at least during the time tested. Among them, 0.1% mometasone furoate glyceroethohyalurosomes were the best formulation to protect cells against oxidative stress and their anti-inflammatory efficacy was confirmed in vivo, being even more effective than the marketed form (Elocom®), as the reduction in the inflammation was even ~15% higher than that achieved with the commercial cream. Selected formulations could be potential candidates as new vehiculation systems for mometasone furoate. The presence of hyaluronic acid in glyceroethohyalurosomes makes them the best candidates in preventing/treating skin inflammatory lesions.

Engineered triamcinolone acetonide loaded glycerosomes as a novel ear delivery system for the treatment of otitis media.

Ear-oriented therapeutics vehiculation strategies are requisites for effective treatment of various otic ailments including otitis media (OM). Conquering minimal permeability of the intrinsic barrier of middle ear; intact tympanic membrane (TM) is still a defiance. In this study, the fabrication of glycerosomes was explored to boost triamcinolone acetonide (TA) delivery to the middle ear via the otic application to improve treatment of OM. Opting a d-optimal design, TA glycerosomes were formulated and optimized using ethanol injection method. The optimized formula was assessed for morphology, viscosity, ex vivo TM permeation and deposition and physical stability. Moreover, OM induction in rats using lipopolysaccharides was conducted, histological and biochemical investigations were performed to assess the therapeutic potential of TA glycerosomes and their tolerability as well. The optimized formula displayed a nanosized value (106.1 ± 2.82), low polydispersity index (0.079 ± 0.04), satisfactory drug entrapment efficiency (80.62 ± 4.41 %), shear thinning behavior and excellent physical stability. Ex-vivo TM permeation and deposition monitoring for 24 h demonstrated greater flux and deposition compared to free drug. More importantly, the in vivo studies demonstrated the supremacy of glycerosomes with respect to tolerability and efficacy in alleviating OM following ototopical application compared to marketed drug. Such therapeutic modality represents a promising option to boost the efficacy of otic drugs, awaiting clinical translation.

Central Composite Optimization of Glycerosomes for the Enhanced Oral Bioavailability and Brain Delivery of Quetiapine Fumarate.

This study aimed to formulate and statistically optimize glycerosomal formulations of Quetiapine fumarate (QTF) to increase its oral bioavailability and enhance its brain delivery. The study was designed using a Central composite rotatable design using Design-Expert® software. The independent variables in the study were glycerol % w/v and cholesterol % w/v, while the dependent variables were vesicle size (VS), zeta potential (ZP), and entrapment efficiency percent (EE%). The numerical optimization process resulted in an optimum formula composed of 29.645 (w/v%) glycerol, 0.8 (w/v%) cholesterol, and 5 (w/v%) lecithin. It showed a vesicle size of 290.4 nm, zeta potential of -34.58, and entrapment efficiency of 80.85%. The optimum formula was further characterized for DSC, XRD, TEM, in-vitro release, the effect of aging, and pharmacokinetic study. DSC thermogram confirmed the compatibility of the drug with the ingredients. XRD revealed the encapsulation of the drug in the glycerosomal nanovesicles. TEM image revealed spherical vesicles with no aggregates. Additionally, it showed enhanced drug release when compared to a drug suspension and also exhibited good stability for one month. Moreover, it showed higher brain Cmax, AUC0-24, and AUC0-∞ and plasma AUC0-24 and AUC0-∞ in comparison to drug suspension. It showed brain and plasma bioavailability enhancement of 153.15 and 179.85%, respectively, compared to the drug suspension. So, the optimum glycerosomal formula may be regarded as a promising carrier to enhance the oral bioavailability and brain delivery of Quetiapine fumarate.

Glycerosomal thermosensitive in situ gel of duloxetine HCl as a novel nanoplatform for rectal delivery: in vitro optimization and in vivo appraisal.

Duloxetine HCl (DXH) is a reuptake inhibitor of serotonin and norepinephrine used to treat the major depressive disorder. Following its extensive hepatic metabolism, acid-labile nature, and limited aqueous solubility, DXH has poor oral bioavailability (40%). The rectal route has been suggested as another route of administration to surmount such challenges. The present study aimed to prepare DXH-loaded glycerosomal (DXH-GLYS) in situ gel for rectal administration to increase DXH permeability and improve its bioavailability. Box-Behnken design (BBD) was adopted to prepare and optimize nanoglycerosomes. The impact of Phospholipon 90G (PL90G), Tween 80 concentrations, and glycerol percentage on encapsulation efficiency, nanoglycerosomal size, % cumulative DXH released, and the cumulative DXH permeated per unit area after 24 h were studied by the design. The pharmacokinetic and pharmacodynamic behavior of optimized formulation was investigated in rats. The formulated DXH-GLYS had a vesicle size ranging between 135.9 and 430.6 nm and an entrapment efficiency between 69.11 and 98.12%. The permeation experiment revealed that the optimized DXH-GLYS in situ gel increased DXH permeation by 2.62-fold compared to DXH solution. Pharmacokinetics studies disclosed that the DXH-GLYS in situ rectal gel exhibited 2.24-times increment in DXH bioavailability relative to oral DXH solution. The pharmacodynamic study revealed that the DXH-GLYS rectal treatment significantly improved the behavioral analysis parameters and was more efficacious as an antidepressant than the oral DXH solution. Collectively, these findings demonstrate that GLYS can be considered a potentially valuable rectal nanocarrier that could boost the DXH efficacy.

Formulation and In Vitro Efficacy Assessment of Teucrium marum Extract Loading Hyalurosomes Enriched with Tween 80 and Glycerol.

The extract of Teucrium marum L. (Lamiaceae) was obtained using the aerial parts of the plant, by means of a maceration process. Verbascoside, caffeic acids derivatives and flavonols were the main components contained in the extract as detected using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) as an analytical method. The extract was successfully incorporated into hyalurosomes, which were further enriched by adding a water cosolvent (glycerol) and a surfactant (Tween 80), thus obtaining glycerohyalurosomes. Liposomes, transfersomes and glycerosomes were prepared as well and used as comparisons. All vesicles were small, as the mean diameter was never higher than ~115 nm, thus ideal for topical application and stable on storage, probably thanks to the highly negative surface charge of the vesicles (~-33 mV). The cryo-TEM images confirmed the formation of close-packed, oligolamellar and multicompartment hyalurosomes and glycerohyalurosomes in which around 95% of the used extract was retained, confirming their ability to simultaneously load a wide range of molecules having different chemical natures. Moreover, the extract, when loaded in hyalurosomes and glycerohyalurosomes was able to counteract the damages induced in the fibroblasts by hydrogen peroxide to a better extent (viability~110%) than that loaded in the other vesicles (viability~100%), and effectively promoted their proliferation and migration ensuring the healing of the wound performed in a cell monolayer (scratch assay) during 48 h of experiment. Overall in vitro results confirmed the potential of glycerohyalurosomes as delivery systems for T. marum extract for the treatment of skin lesions connected with oxidative stress.

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery.

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (V/V) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of -45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.

Topical Administration of Drugs Incorporated in Carriers Containing Phospholipid Soft Vesicles for the Treatment of Skin Medical Conditions.

This review focuses on the improved topical treatment of various medical skin conditions by the use of drugs delivered from carriers containing phospholipid soft vesicles. Topical drug delivery has many advantages over other ways of administration, having increased patient compliance, avoiding the first-pass effect following oral drug administration or not requesting multiple doses administration. However, the skin barrier prevents the access of the applied drug, affecting its therapeutic activity. Carriers containing phospholipid soft vesicles are a new approach to enhance drug delivery into the skin and to improve the treatment outcome. These vesicles contain molecules that have the property to fluidize the phospholipid bilayers generating the soft vesicle and allowing it to penetrate into the deep skin layers. Ethosomes, glycerosomes and transethosomes are soft vesicles containing ethanol, glycerol or a mixture of ethanol and a surfactant, respectively. We review a large number of publications on the research carried out in vitro, in vivo in animal models and in humans in clinical studies, with compositions containing various active molecules for treatment of skin medical conditions including skin infections, skin inflammation, psoriasis, skin cancer, acne vulgaris, hair loss, psoriasis and skin aging.

3D printed ocusert laden with ultra-fluidic glycerosomes of ganciclovir for the management of ocular cytomegalovirus retinitis.

Cytomegalovirus (CMV) retinitisis a vision-threatening disease that principally afflicts immunosuppressed patients. For the management of the disease, Ganciclovir (GCV) is usually administered systemically, where patients may suffer severe untoward effects. The ocularly-applied alternatives are either the intravitreal injections, which are frequently administered due to GCV short half-life, or the sustained-release implants, which require surgical removal upon drug depletion. Both therapies are invasive and should be completed by a medical expert. The objective of this research was to formulate a non-invasive alternative represented in GCV loaded ultra-fluidic glycerosomes (UFGs), which are glycerosomes containing sodium taurocholate as an edge activator (EA), then incorporating the optimal UFGs in polylactic acid (PLA)-based 3D printed ocusert to prolong the release of GCV. The experimental design, the statistical analysis, and the optimization were performed via Design-Expert® software. The optimal formulation (UFGs 6; composed of 600 mg Phosphatidylcholine (PC), 20 mg cholesterol, 0.1:1 weight molar ratio of EA: PC and 1 gm glycerol) possessed nanovesicles (441.70 ± 1.13 nm) that entrapped 69.33 ± 0.28 % of GCV, with zeta potential value of -37.00 ± 0.42 mV and deformability index value of 74.68 ± 0.71. The confocal microscopy results showed the supreme penetration power of UFGs through the rabbit's cornea, compared to edge-activated vesicles and conventional glycerosomes from the laden ocusert. Moreover, the topical application of the ocusert laden with the optimal GCV loaded UFGs to the rabbits' eyes evidenced their safety as per the histopathological findings. Furthermore, a pharmacokinetic study in the rabbit's aqueous humor demonstrated the sustained release of GCV from the ocusert laden with the optimal GCV loaded UFGs over 5 days. Inclusively, the ocusert laden with UFGs could be considered as a non-invasive sustaining drug delivery system of GCV for the management of CMV retinitis.

Extraction, Characterization and Incorporation of Hypericum scruglii Extract in Ad Hoc Formulated Phospholipid Vesicles Designed for the Treatment of Skin Diseases Connected with Oxidative Stress.

An extract of Hypericum scruglii, an endangered endemic plant of Sardinia (Italy), was prepared and characterized. It was loaded in special phospholipid vesicles, glycerosomes, which were modified by adding maltodextrin (glucidex) and a polymer (gelatin or hyaluronan). The corresponding liposomes were also prepared and used as reference. The vesicles disclosed suitable physicochemical features for skin delivery. Indeed, their mean diameter ranged from 120 to 160 nm, they were homogeneously dispersed (polydispersity index ≤ 0.30), and their zeta potential was highly negative (~-45 mV). The vesicle dispersions maintained unchanged characteristics during 60 days of storage, were highly biocompatible, and were able to protect keratinocytes against damages due to oxidative stress induced by treating them with hydrogen peroxide. Vesicles were also capable of promoting cell proliferation and migration in vitro by means of a scratch wound assay. The results confirmed the fruitful delivery of the extract of H. scruglii in glycerosomes modified with glucidex and gelatin and their promising ability for skin protection and treatment.

Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties.

This is a comprehensive review on the use of phospholipid nanovesicles for dermal/transdermal and nasal drug administration. Phospholipid-based vesicular carriers have been widely investigated for enhanced drug delivery via dermal/transdermal routes. Classic phospholipid vesicles, liposomes, do not penetrate the deep layers of the skin, but remain confined to the upper stratum corneum. The literature describes several approaches with the aim of altering the properties of these vesicles to improve their penetration properties. Transfersomes and ethosomes are the most investigated penetration-enhancing phospholipid nanovesicles, obtained by the incorporation of surfactant edge activators and high concentrations of ethanol, respectively. These two types of vesicles differ in terms of their structure, characteristics, mechanism of action and mode of application on the skin. Edge activators contribute to the deformability and elasticity of transfersomes, enabling them to penetrate through pores much smaller than their own size. The ethanol high concentration in ethosomes generates a soft vesicle by fluidizing the phospholipid bilayers, allowing the vesicle to penetrate deeper into the skin. Glycerosomes and transethosomes, phospholipid vesicles containing glycerol or a mixture of ethanol and edge activators, respectively, are also covered. This review discusses the effects of edge activators, ethanol and glycerol on the phospholipid vesicle, emphasizing the differences between a soft and an elastic nanovesicle, and presents their different preparation methods. To date, these differences have not been comparatively discussed. The review presents a large number of active molecules incorporated in these carriers and investigated in vitro, in vivo or in clinical human tests.

Glycerosome of Melissa officinalis L. Essential Oil for Effective Anti-HSV Type 1.

Essential oils are complex mixtures of strongly active compounds, very volatile and sensitive to light, oxygen, moisture and temperature. Loading inside nanocarriers can be a strategy to increase their stability and successfully use them in therapy. In the present study, a commercial Melissa officinalis L. (Lamiaceae) essential oil (MEO) was analyzed by gas chromatography-mass spectrometry, loaded inside glycerosomes (MEO-GS) and evaluated for its anti-herpetic activity against HSV type 1. MEO-GS analyses were prepared by the thin layer evaporation method and they were characterized by light scattering techniques, determining average diameter, polydispersity index and ζ-potential. By transmission electron microscopy, MEO-GS appeared as small nano-sized vesicles with a spherical shape. MEO encapsulation efficiency inside glycerosomes, in terms of citral and ß-caryophyllene, was found to be ca. 63% and 76% respectively, and MEO release from glycerosomes, performed by dialysis bag method, resulted in less than 10% within 24h. In addition, MEO-GS had high chemical and physical stability during 4 months of storage. Finally, MEO-GS were very active in inhibiting HSV type 1 infection of mammalian cells in vitro, without producing cytotoxic effects. Thus, MEO-GS could be a promising tool in order to provide a suitable anti-herpetic formulation.

Investigating the potential of utilizing glycerosomes as a novel vesicular platform for enhancing intranasal delivery of lacidipine.

Lacidipine is a potent dihydropyridine calcium channel blocker used for management of hypertension and atherosclerosis. The drug has low and fluctuating oral bioavailability owing to its extensive hepatic first-pass metabolism and reduced water solubility. Accordingly, this work aimed at overcoming the aforementioned challenges through the formulation of intranasal nano-sized lacidipine glycerosomes. Box-Behnken was successfully employed for the formulation and in vitro optimization of the glycerosomes. Statistical analysis revealed that cholesterol concentration exhibited a significant effect on the vesicle size, while Phospholipon® 90G and glycerol concentrations exhibited significant effects on both entrapment efficiency and deformability index. The optimized formulation showed spherical shape, good deformability, vesicular size of 220.25 nm, entrapment efficiency of 61.97%, and enhanced ex vivo permeation by 3.65 fold compared to lacidipine suspension. Confocal laser scattering microscope revealed higher penetration depth via nasal mucosa for rhodamine labelled glycerosomes (up to 60 µm) in comparison to rhoadamine dye solution (26 µm). In addition, the optimized lacidipine glycerosomes caused significant reduction in methylprednisolone acetate-induced hypertension in rats for up to 24 h in comparison to oral drug suspension. Histopathological assessment showed intact nasal mucosal epithelial lining with no signs of inflammation or necrosis confirming the safety and tolerability of the proposed glycerosomes. The declared results highlights the potential of utilizing the proposed glycerosomes as safe and effective platform for intranasal delivery of lacidipine.

Preparation and optimization of fisetin loaded glycerol based soft nanovesicles by Box-Behnken design.

The present study focused on the development and optimization of glycerosomes for dermal delivery of fisetin. The fisetin loaded glycerosomes formulation was optimized by Box-Behnken design. The independent variables were the lipoid S 100, glycerol, and sonication time, whereas the dependent variables were the vesicles size, entrapment efficiency, and flux. The mechanism of skin penetration of fisetin loaded glycerosomes formulation was determined by the DSC and FTIR studies. Confocal scanning microscopy was used to detect the penetration ability of glycerosomes. The optimized fisetin loaded glycerosomes formulation was converted into a Carbopol® gel matrix, and the latter was analyzed for various parameters. The optimized formulation of glycerosomes presented vesicles size, entrapment efficiency and flux of 138.8 ± 4.09 nm, 86.41 ± 2.95% and 5.04 ± 0.17 µg/cm2/h, respectively. The transmission electron microscopy of optimized fisetin loaded formulation revealed the spherical and sealed structure of glycerosomes vesicles. The confocal study confirmed that the Rhodamine B incorporated glycerosomes penetrated up to deeper layers of skin. The DSC and FTIR studies revealed that the hydration of skin layers and skin lipid fluidization could be the penetration mechanism of fisetin glycerosomes formulation. The optimized fisetin loaded glycerosomes gel formulation presented a flux of 4.24 ± 0.14 µg/cm2/h, and exhibited zero-order release kinetics. The texture analysis of fisetin glycerosomes gel displayed a sufficient hardness, consistency, cohesiveness, and index of viscosity. It was concluded that the prepared fisetin loaded glycerosomes gel was suitable for the dermal application.

Formulation design and optimization of novel soft glycerosomes for enhanced topical delivery of celecoxib and cupferron by Box-Behnken statistical design.

BACKGROUND: The present study describes glycerosomes (vesicles composed of phospholipids, glycerol and water) as a novel drug delivery system for topical application of celecoxib (CLX) and cupferron (CUP) compound. AIM: The goal of this research was to design topical soft innovative vesicles loaded with CLX or CUP for enhancing the efficacy and avoiding systemic toxicity of CLX and CUP. METHODS: CLX and CUP loaded glycerosomes were prepared by hydrating phospholipid-cholesterol films with glycerol aqueous solutions (20-40%, v/v). Box-Behnken design, using Design-Expert® software, was the optimum choice to statistically optimize formulation variables. Three independent variables were evaluated: phospholipid concentration (X1), glycerol percent (X2) and tween 80 concentration (X3). The glycerosomes particle size (Y1), encapsulation efficiency percent (Y2: EE %) and drug release (Y3) were selected as dependent variables. The anti-inflammatory effect of CLX and CUP glycerosomal gel was evaluated by carrageenan-induced rat paw edema method followed by histopathological studies. RESULTS: The optimized formulations (CLX2* and CUP1*) showed spherical morphology under transmission electron microscopy, optimum particle size of 195.4 ± 3.67 nm, 301.2 ± 1.75 nm, high EE of 89.66 ± 1.73%, 93.56 ± 2.87%, high drug release of 47.08 ± 3.37%, 37.60 ± 1.89% and high cumulative amount of drug permeated in 8 h of 900.18 ± 50.24, 527.99 ± 34.90 µg.cm-2 through hairless rat skin, respectively. They also achieved significant remarkable paw edema inhibition in comparison with the control group (p < .05). CONCLUSION: Finally, the administration of CLX2* and CUP1* loaded glycerosomal gel onto the skin resulted in marked reduction of edema, congestive capillary and inflammatory cells and this approach may be of value in the treatment of different inflammatory disorders.