Thin Film Hydration Method Research Articles

Co-delivery of artemisinin and metformin via PEGylated niosomal nanoparticles: potential anti-cancer effect in treatment of lung cancer cells.

Despite the advances in treatment, lung cancer is a global concern and necessitates the development of new treatments. Biguanides like metformin (MET) and artemisinin (ART) have recently been discovered to have anti-cancer properties. As a consequence, in the current study, the anti-cancer effect of MET and ART co-encapsulated in niosomal nanoparticles on lung cancer cells was examined to establish an innovative therapy technique. Niosomal nanoparticles (Nio-NPs) were synthesized by thin-film hydration method, and their physicochemical properties were assessed by FTIR. The morphology of Nio-NPs was evaluated with FE-SEM and AFM. The MTT assay was applied to evaluate the cytotoxic effects of free MET, free ART, their encapsulated form with Nio-NPs, as well as their combination, on A549 cells. Apoptosis assay was utilized to detect the biological processes involved with programmed cell death. The arrest of cell cycle in response to drugs was assessed using a cell cycle assay. Following a 48-h drug treatment, the expression level of hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and 7 genes were assessed using the qRT-PCR method. Both MET and ART reduced the survival rate of lung cancer cells in the dose-dependent manner. The IC50 values of pure ART and MET were 195.2 μM and 14.6 mM, respectively while in nano formulated form their IC50 values decreased to 56.7 μM and 78.3 μM, respectively. The combination of MET and ART synergistically decreased the proliferation of lung cancer cells, compared to the single treatments. Importantly, the combination of MET and ART had a higher anti-proliferative impact against A549 lung cancer cells, with lower IC50 values. According to the result of Real-time PCR, hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and Caspase 7 genes expression were considerably altered in treated with combination of nano formulated MET and ART compared to single therapies. The results of this study showed that the combination of MET and ART encapsulated in Nio-NPs could be useful for the treatment of lung cancer and can increase the efficiency of lung cancer treatment.

NOVEL CB65-LOADED LIPOSOME FORMULATION AS A CHEMOTHERAPEUTIC CANDIDATE FOR OSTEOSARCOMA

Osteosarcoma is common in children and adolescents with high mortality due to rapid progression. Therapeutic approaches for osteosarcoma are limited and may cause side effects. Cannabinoid ligands exert antiproliferative, apoptotic effect in cancer cells via CB1/2 or TRPV1 receptors. In this study, we hypothesized that synthetic specific CB2R agonist CB65 might have an antiproliferative and apoptotic effect on osteosarcoma cell lines in vitro. If so, this agent might be a chemotherapeutic candidate for osteosarcoma, with prolonged release, increased stability and bioavailability when loaded into a liposomal system. We first determined CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT- PCR and FCM. CB65 reduced proliferation in osteosarcoma cells by WST-1 and RTCA. IC50 for MG63 and Saos-2 cells were calculated as 1.11×10-11 and 4.95×10-11 M, respectively. The antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. IC50 of CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively by FCM. CB65 was loaded into the liposomal system by thin film hydration method and particle size, polydispersity index, and zeta potentials were 141.7±0.6 nm, 0.451±0.026, and -10.9±0.3 mV, respectively. The CB65-loaded liposomal formulation reduced MG63 and Saos-2 cell proliferation by RTCA. IC50 of CB65 and CB65-loaded liposomal formulation induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively, by FCM. Scratch width was higher in CB65 and CB65-loaded liposome-treated cells compared to control. In this study, the real-time antiproliferative and apoptotic effect of synthetic specific CB2 agonist CB65 in osteosarcoma cell lines was demonstrated for the first time, and the real time therapeutic window was determined. The CB65-loaded liposomal formulation presents a potential treatment option that can be translated to clinic following its validation within animal models and production under GMP conditions.

Ferrous fumarate nanoliposomes: Formulation, characterization, and diffusion profiles

To assess the effect of cholesterol concentration in the preparation of ferrous fumarate nanoliposome toward its physicochemical properties and stability. Nanoliposomes were produced with cholesterol concentrations of 8, 12, and 16 mg using the thin film hydration method. The ultrasonic dispersion method and mini extruders were used to reduce the particle size. The nanoliposomes were evaluated for their physical properties, encapsulation efficiency, stability, and transport in the in vitro model of skin absorption. Formula 3 showed the smallest size results, with spherical multilamellar vesicle globules with a relatively dense matrix structure and even distribution between particles with a positive zeta potential value with an encapsulation efficiency percentage value of 61.67% ± 0.50 and a cumulative amount penetrated at the second hour of 442.077 mcg/cm2 ± 17.270 with a flux value of 14.575 mcg/cm−2/hour−1. Formulation 3 with higher cholesterol concentration showed better physical characteristics, encapsulation efficiency, and in vitro skin penetration compared to formulations with lower cholesterol concentration.

Preparation and evaluation of a niosomal delivery system containing G. mangostana extract and study of its anti-Acanthamoeba activity.

Garcinia mangostana extract (GME) has severe pharmacokinetic deficiencies and is made up of a variety of bioactive components. GME has proven its anti-Acanthamoeba effectiveness. In this investigation, a GME-loaded niosome was developed to increase its potential therapeutic efficacy. A GME-loaded niosome was prepared by encapsulation in a mixture of span60, cholesterol, and chloroform by the thin film hydration method. The vesicle size, zeta potential, percentage of entrapment efficiency, and stability of GME-loaded niosomes were investigated. The values for GME-loaded niosome size and zeta potential were 404.23 ± 4.59 and -32.03 ± 0.95, respectively. The delivery system enhanced the anti-Acanthamoeba activity, which possessed MIC values of 0.25-4 mg mL-1. In addition, the niosomal formulation decreased the toxicity of GME by 16 times. GME-loaded niosome must be stored at 4 °C, as the quantity of remaining GME encapsulated is greater at this temperature than at room temperature. SEM revealed the damage to the cell membrane caused by trophozoites and cysts, which led to dead cells. In light of the above, it was found that GME-loaded niosomes had better anti-Acanthamoeba activity. The study suggested that GME-loaded niosomes could be used as an alternative to Acanthamoeba's therapeutic effects.

PH-responsive niosome-based nanocarriers of antineoplastic agents.

Differences in pH between the tumour interstitium and healthy tissues can be used to induce conformational changes in the nanocarrier structure, thereby triggering drug release at the desired site. In the present study, novel pH-responsive nanocarriers were developed by modifying conventional niosomes with hexadecyl-poly(acrylic acid)n copolymers (HD-PAAn). Niosomal vesicles were prepared by the thin film hydration method using Span 60, Span 60/Tween 60 and cholesterol as main constituents, and HD-PAA modifiers of different concentrations (0.5, 1, 2.5, 5 mol%). Next, two model substances, a water-soluble fluorescent dye (calcein) and a hydrophobic agent with pronounced antineoplastic activity (curcumin), were loaded in the aqueous core and hydrophobic membrane of the elaborated niosomes, respectively. Physicochemical properties of blank and loaded nanocarriers such as hydrodynamic diameter (Dh), size distribution, zeta potential, morphology and pH-responsiveness were investigated in detail. The cytotoxicity of niosomal curcumin was evaluated against human malignant cell lines of different origins (MJ, T-24, HUT-78), and the mechanistic aspects of proapoptotic effects were elucidated. The formulation composed of Span 60/Tween 60/cholesterol/2.5% HD-PAA17 exhibited optimal physicochemical characteristics (Dh 302 nm; ζ potential -22.1 mV; high curcumin entrapment 83%), pH-dependent drug release and improved cytotoxic and apoptogenic activity compared to free curcumin.

Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. In this study, nano-niosomes were introduced for improving therapeutic index of DXL. In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Novel anti‐evaporative lipid‐based formulation for dry eye disease treatment

Purpose: The majority of dry eye disease (DED) patients suffer from the tear film lipid layer (TFLL) instability issues associated with increased evaporation of water from the ocular surface. Therefore, we developed a liposomal formulation based on selected TFLL lipid classes that would restore the tear film stability and retard the evaporation of the aqueous tear fluid.Methods: The liposomal formulation was prepared by the thin film hydration method and subsequently characterized intermittently by standard techniques for at least 6 months. The mitochondrial metabolic activity (MTT) assay with human corneal epithelial (HCE) cells was utilized to assess the formulation toxicity in vitro. The evaporation resistance properties of the formulation were determined in vitro by the Langmuir trough methods, while a DED cellular model engendered by exposing the HCE cells to benzalkonium chloride (BAC) enabled additional assessment of the in vitro efficacy. In vivo safety was evaluated in rats and rabbits in one‐week studies. The conditions of the animal eyes were assessed by a non‐invasive biomicroscope, an optical coherence tomography, and histological staining of the dissected eyes.Results: The lipid‐based formulation with favourable pharmaceutical and functional properties (e.g., the evaporation resistance, and the promotion of HCE cell recovery after damage) was developed successfully, while also the physical stability of the formulation was found promising. No evidence of toxicity was observed during in vitro and in vivo experiments.Conclusions: The results suggest that the developed formulation is well‐tolerated and possesses properties and a safety profile compatible with ocular administration. Utilized in vitro efficacy models imply that the developed formulation is a promising candidate towards more efficient DED treatment. In vivo efficacy remains to be clarified in future studies.

A design of expert-based development and optimization of voriconazole-loaded aspasomal gel for topical delivery

The research aimed to develop a voriconazole (VRC)-loaded aspasomal gel for topical drug delivery, to minimize the dosing frequency and associated side effects. Aspasomal formulations were prepared using the thin film hydration method and their vesicle size (VS) and entrapment efficiency (%EE) were assessed. Optimization was carried out using a 32-factorial design by design expert software. The optimized batch underwent in vitro anti-fungal activity testing and morphological analysis using high-resolution transmission electron microscopy. This optimized batch was then incorporated into a gel, and various parameters such as drug content, pH, viscosity, spreadability, in vitro diffusion, ex vivo permeation, and in vivo skin irritancy were evaluated. The optimized aspasomal formulation displayed a VS of 171.36 ± 2.3 nm and an %EE of 80.77% ± 1.75%. In vitro drug diffusion and ex vivo permeation studies demonstrated significant release rates of 94.09% and 48.87% after 24 and 12 hours, respectively. The optimized formulation exhibited better in vitro anti-fungal activity against Candida albicans compared to a commercially available formulation. Skin irritancy tests on rat skin showed no signs of erythema or edema, confirming non-irritation. Long-term stability analysis confirmed the formulation’s stability under cold conditions. In conclusion, VRC-loaded aspasomes present a promising alternative for treating skin fungal infections, offering controlled drug release and minimizing adverse effects, ultimately enhancing patient outcomes.

Preparation of a minocycline polymer micelle thermosensitive gel and its application in spinal cord injury.

Neuroprotection is an important approach for the treatment of spinal cord injury (SCI). Minocycline (MC), a known neuroprotective agent, has been utilized for SCI treatment, but its therapeutic effect is limited by instability and low bioavailability. Herein, we developed an innovative micellar thermosensitive hydrogel (MCPP-M-gel) that encapsulates MC in polyethylene glycol (PEG)-poly(lactide-co-glycolic acid) (PLGA) micelles to enhance its therapeutic efficacy in a rat model of SCI. The micelles were synthesized via the thin-film hydration method and characterized for encapsulation efficiency, particle size, zeta potential, and polydispersity index (PDI). MCPP-M-gel demonstrated favorable physico-mechanical properties and extended MC release over 72 hours in vitro without cytotoxic effects on neural crest-derived ectoderm mesenchymal stem cells (EMSCs). Thereafter, MC, MCPP-M, MCPP-M-gel and a blank micellar thermosensitive gel were injected into the injured site of SCI rats. Histopathological evaluation demonstrated that MCPP-M-gel could promote neuronal regeneration at the injured site of the SC after 28 days. Immunofluorescence techniques revealed that MCPP-M-gel increased the expression of neuronal class III β-tubulin (Tuj1), myelin basic protein (MBP), growth-associated protein 43 (GAP43), neurofilament protein-200 (NF-200) and nestin as well as reduced glial-fibrillary acidic protein (GFAP) expression in damaged areas of the SC. In conclusion, this study innovatively developed MCPP-M-gel based on a PEG-PLGA copolymer as a biomaterial, laying a solid foundation for further research and application of MCPP-M-gel in SCI models or other neurodegenerative diseases.

TET1-Lipid Nanoparticle Encapsulating Morphine for Specific Targeting of Peripheral Nerve for Pain Alleviation.

Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia. To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA. Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001). Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.

PEO-b-PCL/Tween 80/cyclodextrin systems: from bioinspired fabrication to possible nasal administration of ropinirole hydrochloride.

In this study, we designed and developed systems composed of poly(ethylene-oxide)-b-poly(ε-caprolactone) block copolymers of different molecular weights and compositions, non-ionic surfactant, and cyclodextrins. The innovation of this study lies in the combination of these diverse biomaterials to create biomimetic and bioinspired drug delivery supramolecular structures. The systems were formed by the thin-film hydration method. Extensive physicochemical and morphological characterization was conducted using differential scanning calorimetry, light scattering techniques, microcalorimetry analysis, high-resolution ultrasound spectroscopy, surface tension measurements, fluorescence spectroscopy, cryogenic transmission electron microscopy images, and in vitro cytotoxicity evaluation. These innovative hybrid nanoparticles were found to be attractive candidates as drug delivery systems with unique properties by encompassing the physicochemical and thermotropic properties of both classes of materials. Subsequently, Ropinirole hydrochloride was used as a model drug for the purpose of this study. These systems showed a high RH content (%), and in vitro diffusion experiments revealed that more than 90% of the loading dose was released under pH and temperature conditions that simulate the conditions of the nasal cavity. Promising drug release performance was observed with all tested formulations, worth further investigation to explore both ex vivo permeation through the nasal mucosa and in vivo performance in an experimental animal model.

Predicting Calcein Release from Ultrasound-Targeted Liposomes: A Comparative Analysis of Random Forest and Support Vector Machine.

This study presents a comparative analysis of RF and SVM for predicting calcein release from ultrasound-triggered, targeted liposomes under varied low-frequency ultrasound (LFUS) power densities (6.2, 9, and 10 mW/cm2). Liposomes loaded with calcein and targeted with seven different moieties (cRGD, estrone, folate, Herceptin, hyaluronic acid, lactobionic acid, and transferrin) were synthesized using the thin-film hydration method. The liposomes were characterized using Dynamic Light Scattering and Bicinchoninic Acid assays. Extensive data collection and preprocessing were performed. RF and SVM models were trained and evaluated using mean absolute error (MAE), mean squared error (MSE), coefficient of determination (R²), and the a20 index as performance metrics. RF consistently outperformed SVM, achieving R2 scores above 0.96 across all power densities, particularly excelling at higher power densities and indicating a strong correlation with the actual data. RF outperforms SVM in drug release prediction, though both show strengths and apply based on specific prediction needs.

Niosome as a promising tool for increasing the effectiveness of anti-inflammatory compounds.

Niosomes are drug delivery systems with widespread applications in pharmaceutical research and the cosmetic industry. Niosomes are vesicles of one or more bilayers made of non-ionic surfactants, cholesterol, and charge inducers. Because of their bilayer characteristics, similar to liposomes, niosomes can be loaded with lipophilic and hydrophilic cargos. Therefore, they are more stable and cheaper in preparation than liposomes. They can be classified into four categories according to their sizes and structures, namely small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs,), multilamellar vesicles (MLVs), and multivesicular vesicles (MVVs). There are many methods for niosome preparation, such as thin-film hydration, solvent injection, and heating method. The current study focuses on the preparation methods and pharmacological effects of niosomes loaded with natural and chemical anti-inflammatory compounds in kinds of literature during the past decade. We found that most research was carried out to load anti-inflammatory agents like non-steroidal anti-inflammatory drugs (NSAIDs) into niosome vesicles. The studies revealed that niosomes could improve anti-inflammatory agents' physicochemical properties, including solubility, cellular uptake, stability, encapsulation, drug release and liberation, efficiency, and oral bioavailability or topical absorption. See also the graphical abstract(Fig. 1).

Preparation and in vitro evaluation of synthetic high-density lipoproteins as parenteral drug delivery system for tamoxifen citrate

The aim of this study was to develop a bioinspired drug delivery system for tamoxifen citrate (TC) based on synthetic high density lipoproteins (sHDL). For this purpose, sHDL nanoparticles were prepared from a mimetic peptide (5A peptide) and different lipids using thin film hydration method followed by sonication and thermal cycling. Various formulation parameters including lipid composition, lipid to peptide ratio, and drug to carrier ratio had a remarkable impact on the properties and the release pattern of the nanoparticles. The optimized formula (F14) displayed a spherical morphology, average diameter of (35.7±12.4) nm, and a zeta potential (ζ) equals to (-48.4± 0.5) mV. The encapsulation efficiency and drug loading of F14 were (96.5±0.7%) and (9.65±0.1%), respectively. Besides, F14 showed a good stability in human plasma for 24 hours. The encapsulation of the lipophilic drug within the hydrophobic core of the nanocarrier enabled a slow drug release from nanoparticles which follows a near zero order controlled mechanism. The promising results of this study opens an avenue for using sHDL as a delivery system for administration of TC intravenously. Therefore, the optimized formula is suggested to be subject for future analyses in terms of in vitro cytotoxicity against breast cancer cells and in vivo evaluation in tumor bearing animals.

Effect of Phase-Change Nanodroplets and Ultrasound on Blood-Brain Barrier Permeability In Vitro.

Phase-change nanodroplets (PCND;NDs) are emulsions with a perfluorocarbon (PFC) core that undergo acoustic vaporisation as a response to ultrasound (US). Nanodroplets change to microbubbles and cavitate while under the effect of US. This cavitation can apply forces on cell connections in biological barrier membranes, such as the blood-brain barrier (BBB), and trigger a transient and reversible increased permeability to molecules and matter. This study aims to present the preparation of lipid-based NDs and investigate their effects on the brain endothelial cell barrier in vitro. The NDs were prepared using the thin-film hydration method, followed by the PFC addition. They were characterised for size, cavitation (using a high-speed camera), and PFC encapsulation (using FTIR). The bEnd.3 (mouse brain endothelial) cells were seeded onto transwell inserts. Fluorescein with NDs and/or microbubbles were applied on the bEND3 cells and the effect of US on fluorescein permeability was measured. The Live/Dead assay was used to assess the BBB integrity after the treatments. Size and PFC content analysis indicated that the NDs were stable while stored. High-speed camera imaging confirmed that the NDs cavitate after US exposure of 0.12 MPa. The BBB cell model experiments revealed a 4-fold increase in cell membrane permeation after the combined application of US and NDs. The Live/Dead assay results indicated damage to the BBB membrane integrity, but this damage was less when compared to the one caused by microbubbles. This in vitro study shows that nanodroplets have the potential to cause BBB opening in a similar manner to microbubbles. Both cavitation agents caused damage on the endothelial cells. It appears that NDs cause less cell damage compared to microbubbles.

Fabricating hybrid DSPC:DOPC:P(OEGMA-co-LMA) structures: Self-assembly as the milestone of their performance

Lipid/polymer nanoparticles are among the most promising hybrid nanoplatforms for pharmaceutical applications, and their many advantages are well established. Despite the efforts, the design parameters that influence their performance have not been deciphered in total yet. In this study, thermodynamic evaluation of lipid and lipid/copolymer bilayers was conducted via differential scanning calorimetry (DSC). Based on their biophysical behavior and by modulating different design parameters for each system, selected lipid/copolymer nanostructures were prepared by the thin film hydration method. The biomaterials of choice were 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and a linear statistical (random) copolymer comprised of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and lauryl methacrylate (LMA). Their features were examined by light scattering techniques, fluorescence spectroscopy, and MTS assay. For the first time DSPC:DOPC:P(OEGMA-co-LMA) hybrid systems were successfully formulated and the most prominent factors influencing their thermodynamic, physicochemical, and toxicological properties were investigated. Our results indicate that self-assembly is pivotal for hybrid systems performance and is mediated via random topology of copolymer, lipid composition, hydrophilic to hydrophobic balance, and lipid to polymer ratio. Having in mind fast clinical translation, we hope this work to contribute to a design road map for efficient lipid/copolymer nanostructure development.

Comparative pharmacokinetic studies of transferosomes loaded gel and pressure sensitive adhesive based patch formulation for transdermal delivery of benztropine mesylate

Oral bioavailability of benztropine mesylate (BZM) is low due to its limited gastric absorption, low biological half-life, and susceptibility to extensive hepatic first pass metabolism. It is an anti-muscarinic drug used for the management of Parkinson's disease. The goal of the present research work was to compare a BZM transferosome-loaded Carbopol 940 gel formulation and an acrylate pressure sensitive adhesive based transdermal patch for their efficacy in transdermal penetration and pharmacokinetic profiles. BZM transferosomes were formulated using the thin-film hydration method. The developed formulation showed a (-) 12.0 mV zeta potential and a mean vesicle size of 138.5 nm. When compared to aqueous BZM solution, transferosomes exhibited a considerable increase in transdermal penetration in an ex vivo study across isolated rat skin. When compared to oral, intravenous, and drug-in-adhesive transdermal patch, in vivo pharmacokinetic investigations in Wistar rats revealed an increase in AUC, Tmax, and MRT and a higher and prolonged drug release from transferosome-loaded gel formulations. The findings suggest that the BZM transferosome-loaded gel might be a better and more patient-friendly alternative to oral administration of BZM for the management of Parkinson's disease.

Nanosized ethosomal dispersions for enhanced transdermal delivery of nebivolol using intradermal/transfollicular sustained reservoir: in vitro evaluation, confocal laser scanning microscopy, and in vivo pharmacokinetic studies

Nebivolol (NBV), a BCS class II anti-hypertensive drug, suffers from limited solubility and oral bioavailability. Nanosized ethosomes were adopted as an approach to solubilize and deliver NBV transdermally, as a substitute to oral route. Ethosomal dispersions were prepared employing thin film hydration method. Formulation variables were adjusted to obtain entrapment efficiency; EE > 50%, particle size; PS < 100 nm, zeta potential; ZP > ±25 mV, and polydispersity index; PDI < 0.5. The optimized ethosomal dispersion (OED) showed accepted EE 86.46 ± 0.15%, PS 73.50 ± 0.08 nm, ZP 33.75 ± 1.20 mV, and PDI 0.31 ± 0.07. It also showed enhanced cumulative amount of NBV permeated at 8 h (Q8) 71.26 ± 1.46% and 24 h (Q24) 98.18 ± 1.02%. TEM images denoted spherical vesicles with light colored lipid bi-layer and dark core. Confocal laser scanning microscopy showed deeply localized intradermal and transfollicular permeation of the fluorolabelled OED (FL-OED). Nanosized FL-OED (<100 nm) can permeate through hair follicles creating a drug reservoir for enhanced systemic absorption. OED formulated into transdermal patch (OED-TP1) exhibited accepted physicochemical properties including; thickness 0.14 ± 0.01 mm, folding endurance 151 ± 0.07, surface pH 5.80 ± 0.15, drug content 98.64 ± 2.01%, mucoadhesion 8534 ± 0.03, Q8 87.61 ± 0.11%, and Q24 99.22 ± 0.24%. In vivo pharmacokinetic studies showed significantly enhanced bioavailability of OED-TP1 by 7.9 folds compared to oral Nevilob® tablets (p = 0.0002). It could be concluded that OED-TP1 can be a promising lipid nanocarrier TDDS for NBV and an efficacious alternative route of administration for hypertensive patients suffering from dysphagia.

TPGS/soluplus® blended micelles: an effective strategy for improving loading capacity of ferroptosis inducer erastin

Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.

Formulation and in-vitro Evaluation of Baclofen loaded Transferosomal Gel

Baclofen is a class of medications called skeletal muscle relaxant. It is a class III drug having low solubility and high permeability used in treating multiple sclerosis symptoms such as spasticity, stiffness, and pain. The current study involves the development and in-vitro evaluation of a Baclofen-loaded transfersomal gel to reduce dosage frequency. Drug and excipient interactions were not detected in the FTIR spectra. Hand shaking modified thin film hydration method was used to developed transfersome formulations, which then consolidated at 0.5% carbopol gel. Optimized BF7 formulation provides higher Entapment efficiency and maximum drug delivery. The prepared formulation had been examined for FTIR, Organoleptic evaluation, Viscosity, Spread-ability, Entrapment Efficacy, Drug content, SEM analysis, Particle size, Zeta potential, Stability testing, and other parameters. The optimised formulation BF7 confirmed Entapment Efficiency ranging from 80.04 to 87.42%, Drug content ranging from 90.26 -95.37%, Vesicle Size of 167.8nm &amp; In-vitro diffusion of 97.48%. The drug release data from the chosen gel demonstrated a good fit with the Higuchis and Zero order release kinetics.&#x0D; Keywords: Transferosomes, vesicular drug delivery system, Thin film hydration method