Thin Film Hydration Research Articles

Exploring peptide dendrimers for intestinal lymphatic targeting: formulation and evaluation of peptide dendrimer conjugated liposomes for enhancing the oral bioavailability of Asenapine maleate.

Asenapine maleate (ASPM) is a second-generation atypical antipsychotic that is approved for treating acute schizophrenia and bipolar disorder in adults by the US FDA. The major downside of ASPM therapy is rapid, extensive first-pass hepatic metabolism following its oral administration with a very low oral bioavailability of < 2%. In this work, we developed ASPM nanoformulations conjugated with ligands such as arginine-glycine-aspartic acid (RGD) and peptide dendrimers (PDs) with the intention of improving the oral bioavailability of the drug by targeting it to the intestinal lymphatic system (ILS). Peptide dendrimers (PDs), both lipidated and nonlipidated, were synthesized by Fmoc solid phase peptide synthesis (SPPS). Reverse phase high performance chromatography (RP-HPLC) was used to purify the synthesized PDs, and the PDs were characterized by differential scanning calorimetry (DSC) electrospray ionization mass spectroscopy (ESI+-MS), Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The thin film hydration method was used to prepare liposomes, and the process variables affecting the liposome parameters were optimized using the Box‒Behnken design (BBD).Liposomes were PEGylated using DSPE-PEG-COOH2000 and further conjugated with ligands (RGD, PD-1 and PD-2) using EDC-NHS chemistry. The formulation was characterized using different spectroscopic techniques. In vitro, cell line studies, such as cytotoxicity, cell uptake, uptake mechanism, and receptor saturation studies, were performed on both Caco2 and Raji-B cells. The pharmacokinetic parameters of the developed liposomal formulation were evaluated using pharmacokinetic studies on Sprague- Dawley (SD) rats. The psychostimulant-induced hyperactivity model was used to evaluate the pharmacodynamic performance of the developed formulations by measuring the reversal of hyperlocomotor activity induced by levodopa-carbidopa.

Development and optimization of multivesicular gefitinib liposomal transdermal system employing lipoid S100 for breast cancer: pharmacokinetics, bioavailability, and skin irritation studies in Wistar rats

Abstract Background Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months. Results The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R 2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV, &lt; 100 nm). Importantly, optimized F3-GEF-LIP-TD showed no signs of edema in Wistar rats. The biodistribution of F3-GEF-LIP-TD was similar to pure GEF and was higher in the liver (p &lt; 0.05). The BA of F3-GEF-LIP-TD was observed to be 74.05 ± 0.11% in comparison with oral GEF-LIP (65.25 ± 0.08%) and pure GEF (58.10 ± 0.17%). Conclusion TFH technique offers stable liposomes with high reproducibility. Our findings imply that GEF-LIP-TD provides enhanced BA and tissue distribution and can be considered as a substitution for orals or in combination for treating breast cancer. Lipoid S100 is a potential lipid for developing stable multivesicular nanoliposomes. Graphical abstract

Inhalable Anti-EGFR Antibody-Conjugated Osimertinib Liposomes for Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths globally. The most extensive treatment is Tyrosine Kinase Inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) overexpression. Osimertinib, a third-generation TKI is approved to target EGFR exon 19 deletions or exon 21 L858R mutations. However, resistance is inevitable due to emergence of triple mutations (sensitizing mutations, T790M and C797S). To overcome this challenge, a combinatorial approach was used wherein Osimertinib liposomes were conjugated with cetuximab (CTX), an anti-EGFR monoclonal antibody, to improve drug efficacy and delivery. Additionally, pulmonary administration was employed to minimize systemic toxicity and achieve high lung concentrations. Methods: Osimertinib liposomes (OB-LPs) were prepared using thin film hydration method and immunoliposomes (CTX-OB-LPs) were prepared by conjugating the OB-LPs surface with CTX. Liposomes were characterized for particle size, zeta-potential, drug loading, antibody conjugation efficiency, in vitro drug release, and aerosolization performance. Further, the in vitro efficacy of immunoliposomes was evaluated in H1975 cell line. Results: Immunoliposomes exhibited a particle size of 150 nm, high antibody conjugation efficiency (87%), efficient drug release, and excellent aerosolization properties with an aerodynamic diameter of 3 μm and fine particle fraction of 88%. Furthermore, in vitro studies in H1975 cells showed enhanced cytotoxicity with CTX-OB-LPs displaying 1.7-fold reduction and 1.2-fold reduction in IC50 compared to Osimertinib and OB-LPs, respectively. The CTX-OB-LPs also significantly reduced tumor cell migration and colonization compared to Osimertinib and OB-LPs. Conclusions: These successful results for EGFR-targeting inhalable immunoliposomes exhibited potential for contributing to greater anti-tumor efficacy for the treatment of non-small cell lung cancer.

Preparation and Characterization of Ozonated Liposomes Loaded with Curcumin: A Potential Approach for Diabetic Retinopathy Treatment

Background: Limitations in drug penetration are overcome by nanotechnology, particularly liposomes, which enhance targeted administration of ocular medications. Liposomes can augment the therapeutic effects of curcumin, a natural compound with positive impacts on the retina. Treatments for eye diseases can also benefit from the antibacterial properties of ozonated oil liposomes. Objectives: This study aims to develop and evaluate ozonated liposomes loaded with curcumin for ocular drug delivery applications, specifically targeting diabetic retinopathy (DR). Methods: Liposomal nanoparticles were prepared using thin-film hydration, incorporating phospholipids, lecithin, cholesterol, ozonated oil, and curcumin. We assessed physicochemical properties including particle size, zeta potential, encapsulation efficiency (EE), and morphology. Drug release profiles and stability studies were also conducted. Results: The optimized liposomes showed a particle size of 84.77 nm, a zeta potential of -16.8 mV, and an EE of 94.73%. The formulation exhibited sustained curcumin release over 24 hours, reaching 82.09% cumulative release. Stability studies indicated minimal changes in key parameters over three months at room temperature. Conclusions: The developed ozonated liposomal formulation demonstrates promising characteristics for curcumin delivery, potentially enhancing its therapeutic efficacy in ocular applications, particularly for DR.

Intratracheal Administration of Itraconazole-Loaded Hyaluronated Glycerosomes as a Promising Nanoplatform for the Treatment of Lung Cancer: Formulation, Physiochemical, and In Vivo Distribution

Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation.

Therapeutic Peptides Encapsulated into Lipid-Based Nanovesicles: Scaling from Lab to Plant

Lipid-based peptide-encapsulated nanovesicles represent a cutting-edge approach in drug delivery systems, offering enhanced stability, targeted delivery, and controlled release of therapeutic peptides. This review explores the comprehensive science and techniques behind the robust formulation and analytical methods for these nanovesicles, spanning from lab-scale research to large- scale manufacturing. Critical aspects include lipid selection, detailing how the choice of lipids impacts the stability and efficacy of the nanovesicles, and various peptide encapsulation techniques, emphasizing methods to achieve high encapsulation efficiency and controlled release. Key processes in vesicle formation, such as thin film hydration, sonication, and microfluidics, are discussed to highlight their roles in producing nanovesicles with consistent size and morphology. The importance of stability studies, including physical, chemical, and thermal assessments, is underscored. Analytical techniques such as Dynamic Light Scattering (DLS), Zeta Potential measurement, High-Performance Liquid Chromatography (HPLC), and Mass Spectrometry (MS) are detailed, showcasing their crucial roles in characterizing nanovesicles and ensuring their quality, safety, and efficacy for pharmaceutical use. The review addresses the challenges and solutions associated with scaling up production, including maintaining consistent product quality, optimizing manufacturing processes, and controlling production costs. It also navigates the regulatory landscape, discussing the stringent guidelines set by agencies such as the FDA and EMA and the necessity of strategic regulatory planning to facilitate market approval. This comprehensive review aims to serve as an in-depth resource for experts in the field, aiding in the translation of lipid-based peptide-encapsulated nanovesicle formulations from bench to bedside, ultimately enhancing therapeutic outcomes and expanding treatment options for various disease. Key Words: Peptide, Amino acid, Degradation, Pharmacokinetics, Peptide encapsulation, drug delivery systems, Peptide Characterization

OPTIMIZATION OF PROCESS PARAMETERS FOR ENHANCING THE SKIN PERMEATION EFFICIENCY OF NISOLDIPINE LOADED ULTRA DEFORMABLE VESICLES IN TRANSDERMAL PATCHES

Objective: The study aimed to address the limitations of oral delivery and enhance the bioavailability of nisoldipine (NSD) through the development of transferosomal transdermal patches containing ultra-deformable transferosomes. Methods: NSD, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. 17 formulations were made using Box Behnken Design, varying Dipalmitoylphosphatidylcholine (DPPC), span-80, and stirring speed, and were evaluated for vesicle size, Polydispersity Index (PDI), and Entrapment Efficiency (EE%). The optimal formulation, selected based on these parameters, was combined into Transdermal Patches (TPs). The patches underwent extensive testing for physicochemical properties, in vitro and ex-vivo permeation, and skin irritancy. Results: The results showed transferosomes with Vesicle Sizes (VS) ranging from 124±2.25 to 400±1.55 nm and EE% from 52.88±0.23 to 90.01±1.58%, with Zeta Potentials (ZP) between-48 to-20 mV. The patch thickness (0.66±0.02 mm) and weight per square inch (382.1±1.69 mg) showed consistent manufacturing, while the Water Vapor Transmission Rate (WVT) (1.54±0.01g/m²/24h), low moisture content (1.07±0.01%), and regulated moisture absorption (3.78±0.01%) maintained formulation stability. In vitro and ex-vivo permeation indicated superior drug permeation for transferosomal patches (NP) compared to plain nisoldipine patches (NP-N), with permeation directly proportional to PEG-400 concentration. Additionally, the transferosomal patches were found to be free from skin irritation. Conclusion: The optimized Niosoldipine transferosomal patch (NP-3) composition displays good folding endurance (FE) 97.67±0.47, required for transdermal systems, and successfully allows drug permeation (DP) at 86.39±2.64% in a short timescale. Hence, the study concludes that transferosomal patches of NSD offer a promising approach for effective transdermal delivery, potentially improving hypertension management by providing a controlled and prolonged drug release.

Development of paroxetine loaded nanotransferosomal gel for intranasal delivery with enhanced antidepressant activity in rats

The aim of this study was to develop paroxetine (PXT) loaded nanotransferosomal gel (PXT-NTFG) for intranasal brain delivery. The process involved fabricating PXT-NTFs (paroxetine-loaded nanotransferosomes) through a thin film hydration method and optimizing them based on parameters such as particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE). The optimized PXT-NTFs exhibited uniform morphology with a PS of 158.30 ± 2.73 nm, low PDI (0.142 ± 0.072), high ZP (21.00 ± 0.75 mV), and excellent EE (88.09 ± 3.40 %). Characterization through various techniques confirmed the incorporation of PXT into the nanotransferosomes and its conversion to amorphous state. Moreover, PXT-NTFG was formulated with suitable viscosity and mucoadhesive properties. In vitro release studies demonstrated sustained drug release from PXT-NTFG at different pH levels as compared to PXT-NTFs and NTF dispersion. Similarly, ex vivo experiments showed 4 folds enhanced drug permeation from PXT-NTFG when compared with PXT conventional gel. Stability studies indicated that the optimized PXT-NTFs remained stable for four months at 4°C and 25°C. Additionally, improved behavioral outcomes, increased neuronal survival rates, and upregulated brain-derived neurotrophic factor (BDNF) expression was observed in lipopolysaccharide (LPS) induced depressed Sprague-Dawley rats after treatment with PXT-NTFG as compared to PXT-dispersion treated and untreated LPS-control groups. Notably, the formulation led to a significant reduction in brain and plasma TNF-α levels. In conclusion, intranasal PXT-NTFG is a promising formulation with sustained drug release, improved brain targeting and enhanced antidepressant activity.

TRANSETHOSOMES FOR ENHANCED TRANSDERMAL DELIVERY OF METHOTREXATE AGAINST RHEUMATOID ARTHRITIS: FORMULATION, OPTIMISATION AND CHARACTERISATION

Objective: The study aimed to develop and optimise Methotrexate (MTX)-loaded Transethosomal Film-Forming Gel (TE FFG) for transdermal delivery to treat rheumatoid arthritis while alleviating the side associated with oral administration. Methods: The Transethosomes (TE) were prepared using the thin film hydration technique and incorporated into an FFG using chitosan. The Box-Behnken Design method was used to analyse the influence of independent variables such as the concentration of soya lecithin, surfactant, and ethanol on parameters including vesicle size, PDI (Polydispersity Index), zeta potential, and entrapment efficiency. The optimised transethosomal suspension was incorporated into the FFG using 3% chitosan and other excipients. In vitro drug release and ex vivo skin permeation of FFG were performed using Franz diffusion cells. Results: The vesicle size, PDI, zeta potential and entrapment efficiency of the optimised formulation of TE were 110.3 nm, 0.352,-14.4 mV and 49.36%, respectively. The Transmission Electron Microscopy (TEM) image showed that the vesicles were uniform and spherical. The in vitro drug release study was higher for Conventional (CL) FFG) than TE FFG and the drug release mechanism was fitted into the Higuchi model. The permeation was higher for TE FFG, with the steady-state flux being 1.55 times greater than the CL FFG. The skin irritation test on Wistar rats revealed no indication of irritation on the skin. The histopathology examination showed a significant reduction in the inflammatory cells in the treated group. Conclusion: Therefore, the results concluded that the formulated MTX-loaded TE FFG could be a potentially promising substitute for the oral delivery of methotrexate

Spray Dried Polymyxin B Liposome for Inhalation Against Gram-Negative Bacteria

This study aimed to provide an alternative and effective delivery system to combat polymyxin B (PMB) toxicity and bacterial resistance through inhalation therapy. PMB was formulated as liposomal dry powder for inhalation using thin-film hydration and spray-dried methods. PMB formulations were characterized physically. The aerodynamic properties were determined using next-generation impactor (NGI). In vitro drug release was done in a phosphate buffer pH 7.4 for 2 h. Cytotoxicity was evaluated by the MTT cell viability assay. Antimicrobiological activities were done using bioassay and flow cytometry. Particle sizes of the spay-dried formulations were between 259.83 ± 9.91 and 518.73 ± 27.08 nm while the zeta potentials ranged between 3.07 ± 0.27 mV and 4.323 ± 0.36 mV. The FT-IR shows no interaction between PMB and other excipients. DSC thermograms revealed amorphousness of the formulated powders and SEM revealed spherical PMB formulations. Similarly, MMAD results were 1.72–2.75 nm, and FPF was 25–26%. The cumulative release of the PMB formulations was 90.3 ± 0.6% within 2 h. The killing kinetics revealed total cell death at 12 and 24 h for Pseudomonas aeruginosa and Escherichia coli respectively. The PMB inhalation liposome showed better activity and was safe for lung-associated cell lines.

Fabrication and application of a dual drug-loaded nanoniosomes encapsulating rutin and berberine: optimization, in vitro and ex vivo evaluation

Rutin and berberine are naturally occurring polyphenols but their usefulness is restricted by their low bioavailability and poor solubility. Thus, by delivering rutin–berberine in the form of niosomes simultaneously and hoped to enhance the permeability through nasal route for the treatment of depression. Thin-film hydration approach was used to generate dual drug-loaded niosomes (rutin–berberine) encapsulating rutin and berberine. Various analytical techniques were used to characterize the morphology, size, compatibility, and leakage of the particles. These techniques included transmission electron microscopy, dynamic light scattering, UV spectrophotometry, and differential scanning calorimetry. The optimized formulation (rutin–berberine optimized niosomal formulation) was subjected to additional characterization for drug release, ex-vivo penetration investigation, confocal laser scanning microscopy, and 2,2-diphenyl-1-picrylhydrazyl assay. The rutin–berberine optimized niosomal formulation analysis showed that the drug release was 76.66 ± 1.24% at 24 hours, the entrapment efficiency was 74.8 ± 2.13% (rutin), and 79.0 ± 3.47% (berberine) and the vesicle size was 72.6 nm with a polydispersion index of 0.208. The antioxidant activity showed 73.67 ± 2.5% which is close to regular ascorbic acid. Studies on permeation ex-vivo revealed that rutin–berberine optimized niosomal formulation had considerably higher permeation (84.89 ± 3.15%) compared to rutin–berberine suspension (37.28 ± 2.33%). Furthermore, rhodamine B-loaded rutin–berberine optimized niosomal formulation appeared to have higher penetration than the control (rhodamine B-solution) according to the confocal laser scanning microscope results of the nasal mucosa. Based on all the experimental data, rutin–berberine optimized niosomal formulations were determined to be a viable and successful intranasal delivery formulation.

Synergistic effect of curcumin and Piperine loaded Niosomal nanoparticles on acute pulmonary toxicity induced by Paraquat in mice.

Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice. The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method. Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286nm), narrow polydispersity index (PDI) (0.19±0.04 to 0.23±0.02), and good stability over 90days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P<0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P<0.001), improving mitochondrial function. The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.

Enhanced Transdermal Delivery of Cilnidpine Via Ultradeformable Vesicle Loaded Patch: Statistical Optimization, Characterization and Pharmacokinetic Assessment.

The study aimed to address the limitations of oral delivery and enhance the bioavailability of Cilnidipine (often prescribed as antihypertensive drug) (CND) through the development of transdermal patches containing ultra-deformable transferosomes. CND, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. Seventeen formulations were made (using Box Behnken Design), varying Soya lecithin, Tween-80, and rotary evaporator's speed, and evaluated for vesicle size, polydispersity index (PDI), and entrapment efficiency (EE %). The better formulation was selected based on these parameters and incorporated into transdermal patches. Physicochemical properties, in-vitro and ex-vivo permeation, and skin irritancy studies were conducted on the patches. Pharmacokinetic studies were conducted using male Wistar albino rats. The study found that the developed transferosomal formulations had vesicle sizes between 185 nm and 401 nm, entrapment efficiency (EE%) between 63% and 92%, and zeta potential ranging from -52 mV to -20 mV. Both in-vitro and ex-vivo permeation studies showed that transferosomal formulations provided significantly better drug permeation than plain Cilnidipine patches, with increased permeation linked to higher PEG-400 concentrations. The transferosomal patches did not cause skin irritation. The optimized formulation exhibited a higher % drug release (85.7±1.5%). In pharmacokinetic studies using male Wistar albino rats, the transferosomal patch CTP-17 demonstrated a higher maximum concentration (Cmax) of 1565.068 mcg/ml and a greater area under the curve (AUC) of 13225.352 μg h/ml compared to oral administration. The study concludes that the transferosomal patches of CND offer a promising approach for effective transdermal delivery, potentially improving hypertension management for prolonged periods in a controlled manner.

Perindopril erbumine-entrapped ultradeformable liposomes alleviate sarcopenia via effective skin delivery in muscle atrophy mouse model

Sarcopenia is a pertinent challenge in the super-aged societies causing reduced functional performance, poor quality of life and increased morbidity. In this study, the potential of perindopril erbumine-loaded ultradeformable liposomes (PE-UDLs) against sarcopenia was investigated. PE-UDLs were prepared by thin-film hydration and extrusion method using egg yolk phosphatidylcholine (EPC) as a lipid bilayer former and Tween 80 or sodium deoxycholate as an edge activator. Owing to the smallest particle size (75.0 nm) and the highest deformability (54.2) and entrapment efficiency (35.7 %), PE-UDLs with EPC to Tween 80 ratio of 8:2 was selected as the optimized formulation. The optimized PE-UDLs showed substantially higher cumulative amount of drug permeated and permeation rate across the rat skin compared to PE solution (485.7 vs. 50.1 µg and 13.4 vs. 2.3 µg/cm2/h, respectively). Topically applied PE-UDLs successfully ameliorated the effects of lipopolysaccharide (LPS)-induced sarcopenia in mice by improving body weight changes, grip strength and muscle weight. Furthermore, PE-UDLs reduced the shrinkage of muscle fibers as demonstrated by higher cross-sectional area than PE solution. PE-UDLs also increased the expression of myosin heavy chain (MHC) protein and reduced the expression of muscle atrophy F-box (Atrogin-1) and muscle ring-finger protein-1 (MuRF1), thereby improving muscles atrophy. In conclusion, these results demonstrate the therapeutic potential of PE-UDLs against sarcopenia.

Development and Optimization of Transferosomal Gel for Efficient Topical Delivery of Berberine Hydrochloride

Background: Berberine is an isoquinoline alkaloid with potent anti-inflammatory effects. However, its therapeutic efficacy is often restricted by its poor solubility, absorption, and permeability, especially in topical applications. Transferosomes are elastic vesicular carriers with high skin permeability values and retention, making them suitable for encapsulating hydrophilic and lipophilic actives. Objective: The objective of this research was to develop a transferosome-based topical gel formulation of Berberine hydrochloride (BER) to improve its skin permeability and anti-inflammatory efficacy. Method: The thin film hydration method was used to formulate the BER transferosomes. The effects of independent variables, amount of BER in lipid phase (X1), and lipid (Phospholipon 90G) to surfactant ratio (X2) on BER entrapment and vesicle size were studied using face-centered central composite design. The characterization was performed using differential scanning calorimetry, transmission electron microscopy, and X-ray diffraction. The optimized batch (F5) was incorporated in Carbopol gel and further investigated for viscosity, in vitro and ex-vivo diffusion, skin retention by tape stripping, and in-vivo anti-inflammatory efficiency. Results: The formulation optimized with 50 mg of drug and a 5:1 lipid-to-surfactant ratio (F5) demonstrated higher drug entrapment efficiency (72.11%) and lower vesicle size (77.9 nm). TEM validated the spherical vesicle morphology, whereas DSC and XRD analysis confirmed the molecular entrapment of BER within the phospholipid vesicles. The transferosomal gel demonstrated improved BER diffusion (0.63 mg/cm2) confirmed by in vitro and ex-vivo diffusion experiments that revealed a 6-fold increase in flux and permeability coefficient (0.1053 mg. cm-2.h-1). The drug release from transferosome gel was non-Fickian in nature (n = 0.6575), indicating an integration of diffusion and erosion processes. Furthermore, BER transferosomal gel displayed substantial anti- inflammatory activity in rats (p &lt; 0.001). result: The independent variables exerted a substantial impact on drug entrapment and transferosome vesicle size. The optimized batch (F5) exhibited 72.11 % of BER entrapment and 77.9 nm vesicle size. DSC studies indicated molecular dispersion of BER in phospholipon G. The change in BER crystalline state was indicated by the XRD study. In vitro, diffusion study of Transferosome gel formulation indicated the sustained release by a non-fickian mechanism. Ex vivo skin permeation revealed significant improvement in BER permeation (p&lt; 0.05). Further, the tape-stripping method revealed higher BER skin permeability. In-vivo anti-inflammatory efficacy of BER transferosome gel was significantly higher as compared to plain BER gel. Conclusion: The findings demonstrated the potential of transferosomal gel as a promising approach for efficient drug delivery and therapeutic efficacy.

Comparative Study of Lycopene-Loaded Niosomes Prepared by Microfluidic and Thin-Film Hydration Techniques for UVB Protection and Anti-Hyperpigmentation Activity.

Niosomes are employed for their improved physical properties and stability and as a controlled delivery system. However, their large-scale production and different preparation methods affect their physical properties. The microfluidic method represents a novel approach to the preparation of niosomes that enables precise control and decreases the preparation time and steps compared to alternative methods. The UVB protection and anti-hyperpigmentation activities of lycopene-loaded niosomes prepared by microfluidic (MF) and novel conventional thin-film hydration (THF) methods were compared. Extract powders from tomatoes (T), carrots (C), and mixed red vegetables (MR) were utilized to prepare lycopene-rich extract-entrapped niosomes. The resulting niosome formulations were characterized by particle size, polydispersity index (PDI), zeta potential, FT-IR spectra, entrapment efficiency, lycopene-release profile, permeation, and stability. The lycopene extract-niosome formulations were evaluated for their potential to provide UVB protection to human keratinocytes (HaCaT) and for their anti-melanogenesis effects on B16F10 melanoma cells. The results indicated that niosomes prepared by the MF method exhibited high uniformity and homogeneity (reflected by a low PDI value) and maintained smaller sizes when processed through a chip utilizing a hydrodynamic flow-focusing (HFF) platform compared to THF niosomes. The release kinetics of all lycopene-niosome formulations followed the Korsmeyer-Peppas model. The FT-IR spectra indicated that lycopene was incorporated into the niosome bilaminar membrane. Moreover, niosomes obtained from MF demonstrated enhanced stability during heating-cooling cycles, along with high UVB protection and anti-melanogenesis effects. Therefore, these developed niosome preparation methods could be effectively applied to topical products.

Enhanced behavioral impact of optimized bupropion-encapsulated bilosomes over traditional niosomes treating depression.

Bupropion (Bpn), an FDA-approved NDRI (norepinephrine-dopamine reuptake inhibitor), poses risks of seizures and liver failure due to its stimulant properties, necessitating the development of alternative formulations. This research aims to develop a Bpn nanoformulation within bilosomal vesicles to enhance therapeutic efficacy at lower doses, using three bile salts, span 20 surfactants, and cholesterol via thin-film hydration. Optimization of bilosomal stability is achieved by trialing various ingredient concentrations, identifying a surfactant-to-cholesterol-to-bile salt ratio of 1.5:1:0.17µM, with sodium cholate (B.SCF) yielding the most stable system. Bpn encapsulated in the optimized bilosomal vesicle (Bpn@B.SC F) demonstrated high encapsulation efficiency of 78.142 ± 11.07% and drug-retaining capacity compared to the niosomal system. The in vitro and in vivo toxicity profile of the product is superior to the niosomal system and shows negligible toxicity with a viability rate of not less than 95%, with a sustained release profile in artificial cerebrospinal fluid (ACSF). In vivo, behavioral analysis on zebrafish revealed that Bpn@B.SC F treatment more effectively improved depressive behavior compared to free Bpn and other treatments, evidenced by increased exploration rates and reduced irregular movements, as shown through statistical and trajectory data. Hence, it is concluded that the bilosomal structure, compared to the niosomal system, is a better carrier of drugs to achieve brain delivery and improve mood.

Exploring the photosensitizing potential of Nanoliposome Loaded Improved Toluidine Blue O (NLITBO) Against Streptococcus mutans: An in-vitro feasibility study.

Streptococcus mutans is a major contributor to dental caries due to its ability to produce acid and survive in biofilms. Microbial resistance towards common antimicrobial agents like chlorhexidine and triclosan has shifted the research towards antimicrobial Photodynamic therapy (PDT). In this context, Toluidine Blue O (TBO) is being explored for its photosensitizing properties against Streptococcus mutans. There is a huge variation in the effective concentration of TBO among the current studies owing to the differences in source of and delivery system TBO as well as the time, power and energy densities of light. The primary objectives of this study are to encapsulate improved Toluidine Blue O (ITBO) in nanoliposomes (NLITBO), characterize it, and evaluate its antibacterial photosensitizing potential against Streptococcus mutans suspensions in vitro. ITBO was synthesised as per Indian patent (number -543908). NLITBO was prepared using the thin-film hydration method. Dynamic light scattering experiment determined the vesicle size, polydispersity index (PDI), and zeta potential. Surface features were characterized by Scanning and Transmission Electron microscopy. ITBO release from NLITBO was assessed using the extrapolation method. The antibacterial activity of the NLITBO was determined by evaluating the zone of inhibition (ZOI) in the Streptococcus mutans culture and comparing with 2% chlorhexidine gluconate. The minimum inhibitory concentration (MIC) of NLITBO as a photosensitizer with red light (wavelength 650nm, power density 0.1 W/cm2, energy density 9-9.1 J/ cm2, 90seconds time) was evaluated against Streptococcus mutans cells by colorimetric method in 96 well plate. Percentage drug loading, loading efficiency, yield percentage, vesicle size, PDI, Zeta potential of NLTBO was reported as 9.3±0.4%, 84.4±7.6%, 73.5%, 123.52 nm, 0.57, -39.54mV respectively. Clusters of uni-lamellar nanovesicles with smooth non-perforated surfaces were observed in SEM and TEM. The size of the vesicle was within 100 nm. At 24 hours, a cumulative 79.81% of ITBO was released from NLITBO. Mean ZOI and MIC of NLITBO (1 μg /ml) were found to be 0.7±0.2 mm, 0.6μg/ml respectively. We have synthesized and encapsulated improved Toluidine Blue O (ITBO) in nanoliposomes (NLITBO) and thoroughly characterized the formulation. The antibacterial efficacy of NLITBO without light was demonstrated by ZOI which is similar to 2% chlorhexidine gluconate. MIC of NLITBO as a photosensitiser along with the optimal light parameter was also proposed in this study. These findings suggested that NLITBO could serve as an effective alternative to conventional antibacterial treatments in managing Streptococcus mutans rich biofilms. It can have potential pharmaceutical application in oral health care.

A Comprehensive Review on Oleic Acid Vesicles: A Novel Approach to Drug Delivery.

The implementation of several innovative drug delivery technologies has made medication distribution more focused and managed in recent years. These days, a vesicular drug delivery system defines the rate of distribution and the site of action in order to improve the action and increase patient compliance; there are various kinds of newly developed vesicular drug delivery systems, including transferosomes, niosomes, aquasomes, ufasomes, pharmacosomes, and phytosomes. Ufasomes are unsaturated fatty acid vesicles with a limited pH range of 7 to 9. They are a suspension of closed lipid bilayers made of fatty acids and their ionized species. The hydrocarbon tails of fatty acid molecules are oriented toward the membrane's inner core, and their carboxyl groups are in contact with water. The two fatty acids that are most frequently employed in the ufasomes' manufacturing process are oleic and linoleic acids. It is a common practice to produce fatty acid vesicles via the thin film hydration process. The manufacture of stable ufasomes is mostly dependent on the choice of fatty acids, amount of cholesterol, pH range, buffer, etc. This article goes into additional detail regarding unsaturated fatty acids' characteristics, benefits, and drawbacks.

Advancing Liposomal Coating Approaches for Improved Anticancer Drug Delivery.

Quercetin, a natural flavonoid with antioxidant, anti-inflammatory, and anticancer properties, faces limitations in clinical application due to its poor solubility and bioavailability. This study presents a novel delivery system utilizing a combination of polyoxyethylene (100) stearyl ether and folic acid to enhance quercetin's effectiveness. We developed folate-conjugated polyoxyethylene (100) stearyl ether-coated liposomes (FA-Brij-LPs) to leverage the unique properties of polyoxyethylene (100) stearyl ether in conjunction with folic acid for targeted delivery. The FA-Brij-LPs were prepared using the thin-film hydration method and characterized for their physicochemical properties, including size, zeta potential, and drug loading capacity. The optimized FA-Brij-LPs exhibited a mean particle size of 147.57 nm, a zeta potential of 32.20 mV, and a drug loading capacity of 9.33%. In vitro studies demonstrated sustained quercetin release and significantly enhanced cellular uptake compared to free quercetin. The Resazurin cell viability assay further revealed superior anticancer efficacy of FA-Brij-LPs. This innovative approach underscores the effectiveness of combining polyoxyethylene (100) stearyl ether with folic acid in enhancing quercetin delivery and its potential applications in cancer therapy.