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Liver disorders present a significant global health challenge, necessitating the exploration of innovative treatment modalities. Liposomal nanocarriers have emerged as promising candidates for targeted drug delivery to the liver. This review offers a comprehensive examination of the mechanisms and applications of liposomal nanocarriers in addressing various liver disorders. Firstly discussing the liver disorders and the conventional treatment approaches, the review delves into the liposomal structure and composition. Moreover, it tackles the different mechanisms of liposomal targeting including both passive and active strategies. After that, the review moves on to explore the therapeutic potentials of liposomal nanocarriers in treating liver cirrhosis, fibrosis, viral hepatitis, and hepatocellular carcinoma. Through discussing recent advancements and envisioning future perspectives, this review highlights the role of liposomal nanocarriers in enhancing the effectiveness and the safety of liver disorders and consequently improving patient outcomes and enhances life quality.

Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles (NAR-HNPs) and NAR on depression induced by streptozotocin (STZ) in rats. NAR-HNPs formula with the highest in vitro NAR released profile, lowest polydispersity index value (0.21 ± 0.02), highest entrapment efficiency (98.7 ± 2.01%), as well as an acceptable particle size and zeta potential of 415.2 ± 9.54 nm and 52.8 ± 1.04 mV, respectively, was considered the optimum formulation. It was characterized by differential scanning calorimetry, examined using a transmission electron microscope, and a stability study was conducted at different temperatures to monitor its stability efficiency showing that NAR-HNP formulation maintains stability at 4 °C. The selected formulation was subjected to an acute toxicological test, a pharmacokinetic analysis, and a Diabetes mellitus (DM) experimental model. STZ (50 mg/kg) given as a single i.p. rendered rats diabetic. Diabetic rat groups were allocated into 4 groups: one group received no treatment, while the remaining three received oral doses of unloaded HNPs, NAR (50 mg/kg), NAR-HNPs (50 mg/kg) and NAR (50 mg/kg) + peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662 (1mg/kg, i.p.) for three weeks. Additional four non-diabetic rat groups received: distilled water (normal), free NAR, and NAR-HNPs, respectively for three weeks. NAR and NAR-HNPs reduced immobility time in forced swimming test and serum blood glucose while increasing serum insulin level. They also reduced cortical and hippocampal 5-hydroxyindoeacetic acid, 3,4-Dihydroxy-phenylacetic acid, malondialdehyde, NLR family pyrin domain containing-3 (NLRP3) and interleukin-1beta content while raised serotonin, nor-epinephrine, dopamine and glutathione level. PPAR-γ gene expression was elevated too. So, NAR and NAR-HNPs reduced DM-induced depression by influencing brain neurotransmitters and exhibiting anti-oxidant and anti-inflammatory effects through the activation PPAR-γ/ NLRP3 pathway. NAR-HNPs showed the best pharmacokinetic and therapeutic results., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3β (GSK-3β) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3β pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Increasing interest in developing antifibrotic therapies became a paramount priority due to the globally raised incidence of deaths secondary to hepatic cirrhosis. This work deals with the development of innovative antifibrotic pirfenidone -loaded lecithin core nanocapsules. This with the intention to target the liver and to increase the drug bioavailability, reducing drug liver toxicity, and studying the associated hepatic microenvironment changes. PFD-loaded lecithin nanocapsules (PFD-LENCs) were prepared using the natural lipoid S45 for its dual benefits of being both a lipid and an amphiphilic surfactant. The selected formulation exhibited in vitro sustained drug release up to 24 h compared to free PFD, which is consistent with the studied pharmacokinetic profile. The studied cytotoxicity of PFD as well as PFD-LENCs exhibited negligible cytotoxicity in normal oral epithelial cells. For exploring the capability of the PFD-LENCs in reaching the liver; in vivo tracing using CLSM, in vivo biodistribution to the vital organs were conducted and electron microscopic examination for depicting nanoparticles in liver tissue was performed. Results revealed the capability of the prepared fluorescent LENC2 in reaching the liver, PFD-LENCs detection in the Disse space of the liver and the significant accumulation of PFD-LENCs in liver tissue compared to the other tested organs. The assessment of the necro-inflammatory, antioxidant and the anti-fibrotic effect of PFD-LENCs (50 & 100 mg/kg) exhibited a significant decrease of liver enzymes, TNF-α, TGF-β, Col-1, α-SMA, and TIMP-1, and a significant increase of catalase enzyme and MMP2 compared to free PFD. EM studies, revealed often detection of dendritic cells in PFD-LENCs (100 mg/kg) treated mice and abnormal collagen structure which can represent an adjunct contribution to the antifibrotic mechanism of PFD-LENCs. In conclusion, the development of this innovative PFD loaded lecithin nanocapsules achieved a targeting ability to the liver, controlled drug release, thereby increase the PFD therapeutic value in downregulating hepatic fibrosis in adjunct with the reduction of liver toxicity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mona Mahmoud AbouSamra reports financial support was provided by Scientific, Technology and innovation funding authority (STDF)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The GC-MS analysis of tea tree oil (TTO) revealed 38 volatile components with sesquiterpene hydrocarbons (43.56%) and alcohols (41.03%) as major detected classes. TTO efficacy is masked by its hydrophobicity; nanoencapsulation can address this drawback. The results showed that TTO-loaded solid lipid nanoparticles (SLN1), composed of glyceryl monostearate (2% w/w ) and Poloxamer188 (5% w/w ), was spherical in shape with a core-shell microstructure. TTO-SLN1 showed a high entrapment efficiency (96.26 ± 2.3%), small particle size (235.0 ± 20.4 nm), low polydispersity index (0.31 ± 0.01), and high negative Zeta potential (-32 mV). Moreover, it exhibited a faster active agent release (almost complete within 4 h) compared to other formulated TTO-SLNs as well as the plain oil. TTO-SLN1 was then incorporated into cellulose nanofibers gel, isolated from sugarcane bagasse, to form the 'TTO-loaded nanolipogel' which had a shear-thinning behavior. Second-degree thermal injuries were induced in Wistar rats, then the burned skin areas were treated daily for 7 days with the TTO-loaded nanolipogel compared to the unmedicated nanolipogel, the TTO-loaded conventional gel, and the normal saline (control). The measurement of burn contraction proved that TTO-loaded nanolipogel exhibited a significantly accelerated skin healing, this was confirmed by histopathological examination as well as quantitative assessment of inflammatory infiltrate. This study highlighted the success of the proposed nanotechnology approach in improving the efficacy of TTO used for the repair of skin damage induced by burns.

The pharmaceutical application of biomaterials has attained a great success. Rapid wound healing is an important goal for many researchers. Hence, this work deals with the development of nanocellulose crystals/lipid nanogels loaded with ofloxacin (OFX) to promote skin repair while inhibiting bacterial infection. Ofloxacin-loaded hybridized nanocellulose/lipid nanogels (OFX-HNCNs) were prepared and evaluated adopting a computational method based on regression analysis. The optimized nanogels (OFX-HNCN7) showed a spherical outline with an encapsulation efficiency (EE), particle size (PS) and zeta potential (ZP) values of 97.53 ± 1.56%, 200.2 ± 6.74 nm and -26.4 ± 0.50 mV, respectively, with an extended drug release profile. DSC examination of OFX-HNCN7 proved the amorphization of the encapsulated drug into the prepared OFX-HNCNs. Microbiological studies showed the prolonged inhibition of bacterial growth by OFX-HNCN7 compared to the free drug. The cytocompatibility of OFX-HNCN7 was proved by Sulforhodamine B assay. Tissue repair was evaluated using the epidermal scratch assay based on cell migration in human skin fibroblast cell line, and the results depicted that cell treated with OFX-HNCN7 showed a faster and more efficient healing compared to the control. In overall, the obtained findings emphasize the benefits of using the eco-friendly bioactive nanocellulose, hybridized with lipid, to prepare a nanocarrier for skin repair.

Research centers around the world are competing to develop therapeutic and prophylactic agents to provide new intervention strategies that could halt or even help slow the progression of the COVID19 pandemic. This requires a deep understanding of the biology and cytopathology of the interaction of SARS-CoV-2 with the cell. This review highlights the importance of electron microscopy (EM) in better understanding the morphology, the subcellular morphogenesis, and pathogenesis of SARS-CoV-2, given its nanometric dimensions. The study also underscores the value of cryo-electron microscopy for analyzing the structure of viral protein complex at atomic resolution in its native state and the development of novel antibodies, vaccines, and therapies targeting the trimeric S spike proteins and the viral replication organelles. This review highlighted the emergence in a short period of time of several viral variants of concern with enhanced transmissibility and increased infectivity. This is due to the elevated affinity of the host receptor with acquired adaptive mutations in the spike protein gene of the virus.Subsequently, to the technical improvement of EM resolutions and the recent promising results with SARS-CoV2 variant structure determination, antibodies production, and vaccine development, it is necessary to maximize our investigations regarding the potential occurrence of immune pressure and viral adaptation secondary to repeated infection and vaccination.

Our work tackles the combined advantages of both nanotechnology and the bioadhesive gel properties which were utilized to design an ocular drug delivery system that is capable to treat ocular inflammation. Nanoparticles encapsulating an antibiotic drug, ofloxacin, were fabricated using emulsion solvent evaporation technique adopting 2 3 full factorial design to evaluate the effect of formulation parameters: that is to say, the molecular weight of the polymer (polycaprolactone), amount of Kolliphor P188, and presence of the charge inducer (chitosan hydrochloride) on the measured responses: drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results show that the optimized LPCL-NP2 formulation (composed of low molecular weight polycaprolactone, 500 mg of Kolliphor P188, 0.25% chitosan hydrochloride, and 50 mg ofloxacin)  displayed a sphere shape with EE%, PS, PDI, and ZP values of 89.73 ± 0.04%, 195.4 ± 13.17 nm, 0.323 ± 0.01, and 55.4 ± 0.66 mV, respectively. DSC study confirmed the amorphous nature of the drug. The optimized nanoparticle formulation was then further incorporated into the following two ocular formulations: gel (LPCL-NP2-G4) and in situ forming gel (LPCL-NP2-ISG4). The penetration of optimized ocular formulations was assessed by confocal laser scanning microscopy. The antimicrobial study was conducted  for the following three ocular formulations: LPCL-NP2 presented as eye drops, LPCL-NP2-G4, and LPCL-NP2-ISG4 as well as the market product using rabbits which were infected in their eyes with Escherichia coli. Results revealed that rabbits treated with LPCL-NP2-ISG4 demonstrated a remarkable antibacterial efficacy and evident low bacterial growth which was additionally assured by the histopathological examination of eye biopsies compared with the other investigated groups. Thus, a novel ofloxacin-loaded nanoparticle formulation based on polycaprolactone is presented in the form of mucoadhesive non-irritating in situ forming ocular gel possessing a superior antibacterial activity. Graphical abstract., (© 2020. Controlled Release Society.)

Propranolol (PPL) administered orally is considered as the first line drug for the treatment of infantile hemangioma, however several systemic adverse effects limit its use. For this reason, our work tackles the development and evaluation of PPL loaded chitosan nanoparticles (NPs), as an effective alternative for the treatment of infantile hemangioma. PPL -NPs were prepared using the double emulsion technique and the influence of the formulation variables on drug entrapment efficiency (EE), particle size (PS), percent released after 24 h (%R 24h ) and zeta potential (ZP) were optimized using full factorial design. Two systems, namely F3 and F28 showing highest E.E., ZP and %R 24h with lowest PS, were fully characterized for DSC and TEM and incorporated into hydrogel with adequate viscosity. After ensuring safety for the selected nanoparticle, the hydrogel containing the optimized system was applied topically to rats. The in-vivo skin deposition in rats showed an accumulation of propranolol from the lecithin/chitosan nanocarrier by 1.56-1.91-fold when compared to the drug solution. The obtained result was further supported by the confocal laser scanning microscopy which showed fluorescence across the skin. PPL-HCL-loaded lecithin/chitosan nanoparticles could be considered as a potential candidate for treating infantile hemangiomas (IH) by maintaining therapeutic concentration topically while minimizing systemic side effects., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Ciclopirox olamine (CPO) is a topical wide-spectrum antimycotic agent that possesses antifungal, antibacterial and anti-inflammatory activities. Loading CPO into a hybridized vesicular system is expected to enhance its buccal permeation and hence, therapeutic activity, whereas the frequent administration and side effects are reduced. Vesicular systems with high penetration ability were prepared based on cholesterol, Lipoid S45 or Phospholipon 90H, with span 60 while incorporating a penetration enhancer (Labrafac or labrasol) followed by full assessment of their size, entrapment efficiency, and drug release profiles. The optimum formulation, composed of Lipoid S45 and Labrafac, possessed the smallest vesicle size (346.1 nm), highest entrapment efficiency (94.4%), and sustained CPO release pattern, and was characterized for its morphology and thermal properties. This powerful mixture of the penetration enhancers (Lipoid S45 and Labrafac) in the designed hybridized vesicles was thoroughly investigated for their characteristics after being incorporated in bioadhesive gel. Moreover, enhanced antifungal activity was demonstrated either upon testing the designed formulation on agar plates or in vivo upon treating infected rabbits with the proposed formulation. Results suggest that the presented bioadhesive gel incorporating the CPO-loaded vesicles can be a promising delivery system that can offer a prolonged localized antifungal treatment with enhanced therapeutic effect.

Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation parameters on drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were investigated using a full factorial design. The results show that the optimized CDX-CSNP1 composed of low molecular weight chitosan (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 ± 0.02, 408.30 ± 53.17 nm, 0.458 ± 0.048 and 22.80 ± 0.57 mV, respectively. DSC and XRD studies confirmed the amorphous nature of the drug. After ensuring the safety and non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial activity was evaluated using a rat skin infection model against Staphylococcus aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group revealed a remarkable accelerated wound healing process and bacterial clearance which was further confirmed by the histopathological examination of skin biopsies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

The present study involves the preparation of cubic liquid crystalline nanoparticles (cubsomes) for liver targeting to assess the potential of a formulated bioactive polysaccharide isolated from the hot aqueous extract of Ulva fasciata as an alternative natural agent with anti-hyperlipidaemic activity. Cubosomal nanoparticles were prepared by disrupting the cubic gel phase of the polysaccharide and water in the presence of a surfactant. Different lipid matrices and stabilizers were tested. All the formulations were in the nanosize range and showed sufficient negative charge to inhibit the aggregation of the cubosomes. Drug entrapment efficiencies (EEs%) were determined and in vitro release studies were performed. Transmission electron microscopy (TEM) and differential scanning calorimetry were used to analyze the loaded cubosomal nanoparticles containing glyceryl monostearate (GMO 2.25 g), poloxamer 407 (0.25 g) and 50 mg of the polysaccharide. A preclinical study comparing the cubic liquid crystalline nanoparticles containing polysaccharide to fluvastatin as a reference drug in hyperlipidaemic rats was conducted. The rats treated with the polysaccharide- loaded cubosomes showed significant decreases in total cholesterol (TC), triglycerides (TG) and total lipid (TL) compared to the untreated HL rats. In addition, oxidative stress and antioxidant biomarkers were measured in the HL rats. Compared to the untreated HL rats, the cubosome treated rats showed a significant reduction in malondialdehyde (MDA), whereas insignificant changes were detected in nitric oxide (NO), glutathione (GSH) levels and total antioxidant capacity (TAC). Further, vascular and intercellular adhesion molecules (VCAM, ICAM), and myeloperoxidase were demonstrated. A histopathological examination was conducted to study the alterations in histopathological lesions and to document the biochemical results. In conclusion, this study demonstrates the superiority of using a natural lipid regulator such as polysaccharide loaded cubosomes instead of fluvastatin .

Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary ointment bases and insufficient penetration through the infected skin layers the need to incorporate the drug in a more suitable pharmaceutical form has evolved. A provesicular system is one such form that can solve these problems. Once in contact with the skin, dilution with moisture occurs and the provesicular system rapidly transforms into a vesicular one. Provesicular systems were prepared according to full-factorial experimental design. Plain provesicular systems were compared with systems containing Phospholipon 80 H and Lipoid S45 as penetration enhancers. Design expert software was used to analyze the effect of formulation variables (type of Span used as well as the presence or the absence of the penetration enhancer and its type) on the dependent variables: percent encapsulation efficiency (EE%), vesicle size and percent in vitro drug released). Three formulations were chosen; a plain provesicular system (PV-2), one containing Phospholipon 80H (PV-6) and another containing Lipoid S45 (PV-10) with the goal to reveal the effect of penetration enhancer on morphology, rheological properties and ex vivo permeation using confocal laser scanning microscopy (CLSM). Analysis of CLSM results showed that the penetration enhancing effect for the tested formulations followed the order PV-10 > PV-6 > PV-2. Promising clinically active treatment for tinea patients could be expected as shown by the in vivo permeation results for the provesicular systems as suggested by the CLSM results.

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8 ± 18.69 to 797.7 ± 12.45 nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC 0-48 hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.