UNASSIGNED: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma.
UNASSIGNED: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time.
UNASSIGNED: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization.
UNASSIGNED: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic.
UNASSIGNED: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.
Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

BACKGROUND: Rheumatoid arthritis is indeed a constant, progressive autoimmune disease that acts on the synovial membrane, distinguished by joint pain, swelling, and tenderness. Sulfasala- zine belongs to BCS Class IV having low solubility and low permeability. To overcome the issue and provide a localized effect Cubosomes were chosen for the transdermal drug delivery system.
OBJECTIVE: The primary objective of this investigation was to pass on sulfasalazine-loaded cubo- somes over the skin to treat rheumatoid arthritis. On the way to overcome this issue of oral sulfasala- zine and provide localized effect, Cubosomes were chosen for the transdermal drug delivery system.
METHODS: Sulfasalazine-loaded cubosomes were prepared by the top-down method using GMO and Poloxamer 407. Different concentrations of lipid and surfactant were used in the formulation using 32 full factorial designs. The prepared formulations were assessed for p.s, z,p, %EE, FTIR, SEM, in- vitro release, ex-vivo permeation, and deposition studies with pH 7.4 phosphate buffer saline.
RESULTS: The particle size varies between 65 nm to 129 nm, while the negative zeta potential ranged from - 18.8 mV to -24.8 mV. The entrapment efficiency was between 87% and 95%. The formulations\' in-vitro drug release was carried out for 12 hours. The optimized formulation showed a controlled release of sul- fasalazine and better ex-vivo permeation and deposition properties than sulfasalazine suspension.
CONCLUSIONS: Overall study findings support the possibility of applying transdermal sulfasalazine- loaded cubosomes to alleviate rheumatoid arthritis.

This study aims to improve the RXB bioavailability using hybrid nanoparticles. A modified melt dispersion technique created different formulas with varying GMO-SAIB: RXB and GMO: SAIB ratios, with fixed GMO-SAIB: poloxamer 407 ratios. The PS, PDI, ZP, and EE were measured to determine the optimal formula, which was selected using Design-Expert™ software. The optimized formula was lyophilized and tested for PS, PDI, ZP, and EE. The chosen lyophilized formula (L4) was characterized using FTIR, DSC, PXRD, dissolution studies, and pharmacokinetics studies. The study found correlations between variables and identified how GMO-SAIB concentration affects drug encapsulation. The dissolution parameters were calculated, including % Q5 and % DE). The % Q5 values were 68.4 ± 1.7% and 89.7 ± 3.6% for Xarelto and L4 tablets, respectively. The % DE values were 89.7 ± 0.4% and 97.5 ± 2.1% for Xarelto and L4 tablets, respectively. The AUC values were 2117.0 ng.h/mL (±77.3) and 3919.4 ng.h/mL (±134.8) for Xarelto and L4 tablets, respectively. The Cmax values were 241.3 ng/mL (±21.0) and 521.5 ng/mL (±91.5) for Xarelto and L4 tablets, respectively. In conclusion, the study found that using GMO-SAIB as co-formers effectively enhanced the bioavailability of RXB. The authors recommend using the hybrid nanoparticles technique and suggest further research to enhance its effectiveness for drug delivery.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Herein, a new approach for glycerol monooleate (GMO) was developed. GMO was synthesized via the esterification method using self-made sodium oleate and 3-chloro-1,2-propanediol as reactants, tetrabutylammonium bromide as the catalyst, and toluene as the solvent. The effects of the reaction molar ratio, type and amount of catalyst, and reaction temperature and time on the yield were investigated. Results showed that the optimal process conditions for synthesizing GMO were as follows. The molar ratio of sodium oleate to 3-chloro-1,2-propanediol was 1:2, the reaction temperature was 115°C, the reaction time was 6 h, weight of toluene was 25 g, and the catalyst dosage was 3.5%. Under these conditions, high-purity GMO was synthesized with a yield of 89.02%.

Because of the extraordinary advancements in biomedical nanotechnology over the last few decades, traditional drug delivery systems have been transformed into smart drug delivery systems that respond to stimuli. These well-defined nanoplatforms can boost therapeutic targeting efficacy while reducing the side effects/toxicities of payloads, which are crucial variables for enhancing patient compliance by responding to specific internal or external triggers. Cubosomes are lipid-based nano systems that are analogous to well-known vesicular systems, such as lipo- and niosomes. They could be used as part of a unique drug delivery system that includes hydro-, lipo-, and amphiphilic drug molecules. In this review, we critically analyze the relevant literature on cubosomesregarding theories of cubosomeself-assembly, composition, and manufacturing methods, with an emphasis on tumor-targeted drug delivery applications. Due to the bioadhesive and -compatible nature of cubosome dispersion, this review also focuses on a variety of drug delivery applications, including oral, ophthalmic and transdermal.

Bacterial biofilms account for up to 80% of all community-acquired infections for which bacterial eradication is currently not achievable using conventional antimicrobial treatments. The protective matrix that engulfs biofilm-associated bacteria frequently renders antibiotics ineffective. Glycoside hydrolases are a class of enzymes that break down the biofilm matrix, thereby increasing the effectiveness of antibiotics. Herein, nanostructured liquid crystals composed of glyceryl monooleate (GMO) were investigated as an infection responsive delivery system for alginate lyase (glycoside hydrolase) and gentamicin (antibiotic) to treat Pseudomonas biofilms. The presence of Pseudomonas lipase triggered the release of alginate lyase and gentamicin from the GMO liquid crystals. Treatment with the liquid crystals containing alginate lyase and gentamicin resulted in a greater than 2-log reduction in mucoid Pseudomonas aeruginosa (clinical isolate) biofilm. The anti-biofilm activity of alginate lyase and gentamicin from the liquid crystals was sustained for 2 days and equivalent to the respective unformulated solution treatments. Accordingly, GMO based liquid crystals are a promising responsive delivery system for alginate lyase and gentamicin to combat topical Pseudomonas infections.

UNASSIGNED: In a recent study, in our laboratory, primary unconjugated bile acids, commonly found in humans, chenodeoxycholic acid (CDCA), have been shown to improve stability of nanoencapsulated lipophilic drugs and improve their release profile after oral administration likely via electrokinetic stabilisation. Hence, this study aimed to examine the effects of CDCA on exerting similar effects on hydrophilic drugs.
UNASSIGNED: Various CDCA-based formulations were produced for the orally administered hydrophilic drug, metformin. Analyses of these formulations included electrokinetic potentials, topography, drug and CDCA formulation contents, nano size distribution, heat-induced deformation and outer-core expansion indices, release profiles, shell-resistance ratio, and thermal and chemical indices. With the drug\'s main target being pancreatic beta-cells, the formulations\' effects on cell viability, functions and inflammatory profiles were also investigated.
UNASSIGNED: CDCA-based metformin formulations exhibited improved stability and release profiles via thermal, chemical and electrokinetic effects, which were formulation-dependent suggesting potential applications of CDCA in the oral targeted delivery of hydrophilic drugs.

Acyclovir (ACR) is considered the gold standard drug for the treatment of skin viral infections caused by the herpes simplex or varicella-zoster virus. However, topical therapy with ACR is hindered by its poor skin penetrability, thus necessitating high doses and frequent administrations. This study was proposed to formulate a modified lipid-coated chitosan nanocomplexes (LCNCs) of acyclovir (ACR), containing span 80 and TPGS, to boost the dermal delivery of ACR and improve the therapeutic outcomes. LCNCs were formulated through a self-assembly method, and the statistical analysis and the optimization were performed via a general 23 factorial design. Three formulation variables were selected; namely, the amount of chitosan (A), the amount of glyceryl monooleate (GMO) (B), and span 80: D-α-tocopheryl polyethylene glycol succinate (Vitamin ETPGSorTPGS) ratio (C). Four measured attributes were determined; viz., the particle size (PS) in nm, the polydispersity index (PDI), the zeta potential (ZP) in mV, and the entrapment efficiency percentages (EE%). The optimal formulation (LCNCs 8), formulated with 600 mg chitosan, 120 mg GMO, and 3:1 span 80: TPGS ratio, possessed PS of 177.50 ± 1.41 nm, PDI value of 0.28 ± 0.02, ZP of -10.70 ± 0.85 mV, and EE% of 77.20 ± 2.40 %, and was able to sustain ACR release over 24 h. Transmission electron microscopy displayed LCNCs architecture as a polymeric core of chitosan with a lipid coat of GMO, and the solid-state characterization results confirmed the dispersion of ACR in LCNCs. The ex vivo permeation study and the in vivo dermatokinetics profile verified the boosted accumulation of ACR in the skin via LCNCs, while the confocal laser scanning microscopy revealed the heightened penetrability of LCNCs. The topical application of LCNCs demonstrated a safe profile via the modified Draize test and histopathological examinations. Inclusively, ACR-loaded LCNCs could be a promising topical formulation with an advanced dermal delivery status for the treatment of skin viral infections.

OBJECTIVE: Candesartan cilexetil (CC), a prodrug of candesartan (CDT), is a class II BCS drug that suffers from poor oral bioavailability because of low aqueous solubility, P-gp efflux and first-pass metabolism. The absolute bioavailability reported for CC was only 15% and the methods to increase it remain elusive, thus the aim of our work was to prepare new CC-loaded niosomes encompassing, for the first time, glycerol monooleate GMO (Peceol™), as P-gp efflux inhibitor and promoter of lymphatic transport with Span™ 60 as bioenhancer. The prepared niosomes were further coated with chitosan for augmenting the CC oral absorption.
METHODS: The niosomes were prepared by thin film hydration method through quality by design approach, using two levels of each of three critical process parameters (CPPs), namely, XA (the molar ratio of surfactant mixture to cholesterol) at a ratio of 1:1 or 2:1; XB (the molar ratio of Span™ 60 to Peceol™) at a ratio of 1:1 or 2:1; and XC (the drug amount) at 15 mg or 30 mg. The investigated critical quality attributes (CQAs) were entrapment efficiency percent, particle size, and polydispersity index. The optimized uncoated and chitosan coated formulations were subjected to DSC and stability study. In vitro drug release, biocompatibility with Caco-2 cells and lastly the absolute bioavailability evaluation in rats were assessed.
RESULTS: The physical properties of the optimized and stable niosomes were satisfactory. The ingredients were compatible with each other and biocompatible with Caco-2 cells. The synergistic combination of Peceol™ and Span™ 60 probably surmounted the P-gp efflux with an increase in oral absolute bioavailability of niosomes to five times that of CC suspension.
CONCLUSIONS: The new niosomal formulations of CC containing Peceol™ with Span™ 60 and cholesterol either uncoated or coated with chitosan were a successful paradigm in achieving high oral absolute bioavailability and increased Caco-2 cells biocompatibility.