A reduction-sensitive cationic bolaamphiphile bearing N-methylpyridinium terminal groups and a central disulfide bridge was synthesized and shown to self-assemble in water into stable vesicles with diameters of 200-250 nm. The vesicles undergo redox-triggered disassembly in the presence of tris(2-carboxyethyl)phosphine (TCEP), and analogous behavior was also observed using glutathione (GSH), supporting their responsiveness to reductive environments. Their potential as nanocarriers was evaluated using the photosensitizer Rose Bengal (RB) and the chemotherapeutic agents paclitaxel (PTX) and camptothecin (CPT) in A549, HT29, and MCF7 cancer cell lines. The vesicles significantly enhanced the cellular uptake of RB, as demonstrated by flow cytometry and confocal microscopy. Colocalization analysis with MitoTracker Green further supported preferential mitochondrial localization of RB fluorescence. This was accompanied by a pronounced increase in photodynamic activity upon light irradiation in A549 and MCF7 cells, where apoptosis was identified as the dominant cell-death pathway. In addition, vesicle-based formulations of PTX and CPT improved their cytotoxicity across all tested cell lines, with a particularly strong effect observed in HT29 cells under the experimental conditions employed. Overall, these pyridinium-based bolaamphiphilic vesicles represent a versatile redox-responsive delivery platform capable of enhancing intracellular delivery and therapeutic performance of both photosensitizers and poorly water-soluble anticancer drugs.
Coenzyme Q10 (CoQ10), a lipophilic benzoquinone essential for mitochondrial energy metabolism and intrinsic antioxidant defense, exhibits substantial therapeutic potential in cardiovascular, neurological, dermatological, and metabolic disorders. However, its pronounced hydrophobicity, high molecular weight (863.34 g/mol), thermolability, and extremely poor aqueous solubility significantly limit its oral and topical bioavailability, rendering conventional formulations insufficient for optimal therapeutic outcomes. This review provides a contemporary overview of advanced delivery strategies designed to overcome these limitations, with a primary focus on nano-vesicular drug delivery systems and bioavailability enhancement approaches. The physicochemical and biological characteristics of CoQ10 are discussed to clarify the major barriers restricting its effective administration. Particular emphasis is placed on nano-vesicular platforms, including niosomes, transfersomes, ethosomes, transethosomes, phytosomes, and cubosomes, highlighting their structural attributes, encapsulation efficiency, permeability enhancement, and reported preclinical and clinical outcomes. Additionally, complementary penetration-enhancing approaches, such as chemical permeation enhancers, microneedles, iontophoresis, and biomimetic or hybrid systems, are examined for their role in improving CoQ10 delivery. The relationship between formulation design and biological performance is critically evaluated to provide mechanistic insight into therapeutic enhancement. Available clinical evidence suggests improved systemic absorption and therapeutic efficacy of CoQ10 through lipid-based and nano-vesicular systems, particularly liposomal and phytosomal formulations. Finally, key translational challenges, including formulation stability, biological barriers, manufacturing scalability, and regulatory considerations, are discussed alongside emerging trends such as stimuli-responsive nanocarriers, mitochondria-targeted systems, and computationally guided formulation development. Collectively, these advances highlight the potential of nano-enabled delivery systems to overcome CoQ10 pharmacokinetic limitations and facilitate future clinical translation.
Gentamicin is a widely used aminoglycoside antibiotic; however, its clinical use is limited by dose-dependent nephrotoxicity. Liposomal drug delivery systems may reduce toxicity while preserving antibacterial efficacy. This study aimed to comparatively evaluate the nephrotoxic and antimicrobial effects of free and liposomal gentamicin in a rat model. Rats were divided into control, free gentamicin (FGT; 100 mg/kg), and liposomal gentamicin (LipGT; 100 mg/kg) groups administered for 7 days. Renal function parameters, oxidative stress biomarkers, pro-inflammatory cytokines, renal injury markers, and gene expression levels were analyzed. Free gentamicin significantly increased serum BUN and creatinine levels, oxidative stress, inflammatory cytokines, and renal injury biomarkers. Liposomal gentamicin attenuated these alterations, demonstrating a protective effect. Creatinine levels showed partial normalization, whereas BUN exhibited a distinct response. Liposomal treatment partially restored SIRT3 expression but did not normalize PAX2. Histopathological findings supported these results. Antimicrobial analysis revealed preserved activity against Escherichia coli but reduced efficacy against Staphylococcus aureus. Liposomal encapsulation mitigates gentamicin-induced nephrotoxicity while partially maintaining antibacterial activity, suggesting a promising strategy to improve drug safety.
PEGylated liposomal nanocarriers have emerged as a promising drug delivery platform for improving the pharmacokinetic performance and systemic circulation of poorly water-soluble anticancer drugs. In this study, Axitinib-loaded PEGylated liposomes (F11-PEGliposome) were prepared and evaluated for the potential treatment of breast cancer. Liposomes were prepared by optimization with a Box-Behnken design and subsequently extruded using lipid extrusion to obtain a vesicle size of 158.6 ± 2.4 nm, PDI of 0.12 ± 0.01, zeta potential of -1.2 ± 0.5, and entrapment efficiency of 79.9 ± 1.8%. In 2D cell culture studies, F11-PEGliposome showed enhanced anticancer activity with IC50 values of 1.7- and 2.13-fold lower than free Axitinib. Cellular uptake, ROS generation, JC-1 mitochondrial membrane potential, and AO/EB staining assays exhibited enhanced internalization and apoptosis induction. In 3D spheroid models, F11-PEGliposome exhibited deep penetration in the tumor, significant growth inhibition, increased ROS production, and pronounced apoptotic cell death. In-vivo pharmacokinetic and biodistribution studies showed extended circulation, enhanced bioavailability, and prolonged half-life. Reduced hepatic and renal toxicity was evident as shown by histopathological evaluation and decreased serum AST, ALT, creatinine, and BUN levels. Western blot analysis revealed dose-dependent increases of cleaved caspase-3 and cleaved PARP1, supporting the conclusion of apoptosis.
Chitosan-polyethylene glycol (CS-PEG)-modified long-circulating liposomes were developed and loaded with tanshinone I (TaI@CS-PEG-L) to overcome its poor solubility and low bioavailability, as well as enhance the lipid-lowering efficacy of atorvastatin (At) and mitigate its tissues toxicity. After synthesis of CS-PEG copolymer, it was characterized with infrared and proton nuclear magnetic resonance. Thin-film hydration was used to prepare TaI@CS-PEG-L before optimization was performed using Box-Behnken design. Optimal liposomal formulation was obtained when mass ratio of lecithin:cholesterol:TaI mass ratio was 12:1:1 along with 0.2% CS-PEG, which displayed appropriate particle size (117.41 nm), polydispersity index (0.182), zeta potential (+17.31 mV), encapsulation efficiency (93.15%), and drug loading (5.19%). Besides, the liposomal preparation exhibited good long-term storage stability (over 30 days at 4 °C and 25 °C) and satisfactory gastrointestinal stability in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids for 4 h. TaI@CS-PEG-L displayed increased cellular uptake and in vitro release compared with free TaI and unmodified liposomes. Regarding pharmacokinetic studies, TaI@CS-PEG-L increased AUC0-ₜ, t1/2, and Cmax in rats by 7.26-fold, 2.43-fold, and 3.12-fold, respectively, which indicates significantly enhanced oral bioavailability. TaI@CS-PEG-L monotherapy markedly lowered serum lipid levels in hyperlipidemic mice, thereby improving liver function indices, and alleviating pathological liver injury. TaI@CS-PEG-L demonstrated synergistic lipid-lowering effects and efficiently reversed At-induced hepatic and pancreatic injuries after combination with At, thus outperforming free TaI and TaI@L. Therefore, CS-PEG-modified long-circulating liposomes could efficiently address delivery challenges of TaI, thereby yielding a formulation that could potently lower serum lipid levels and protect liver against injury. The findings of this study offer a promising 'efficacy-enhancing and toxicity-reducing' strategy for potential treatment of hyperlipidemia in the clinics.
Pegylated liposomal doxorubicin (PLD) is the first FDA-approved liposomal product in the oncology field and has been extensively investigated over the years. Although PLD has been extensively studied, measurement of unencapsulated doxorubicin in tissues remains technically challenging, limiting detailed interpretation of tissue pharmacokinetics/pharmacodynamics (PK/PD) and toxicokinetics/toxicodynamics (TK/TD) relationships. Here, we present a novel approach to quantify unencapsulated doxorubicin in tumors and other tissues. Our method employs the gentleMACS Dissociator for tissue homogenization to prevent liposome disruption. While homogenization with conventional zirconia beads increased the unencapsulated doxorubicin fraction by 4.2- to 13.3-fold, homogenization with the gentleMACS Dissociator resulted in no increase in unencapsulated doxorubicin, demonstrating superior preservation of PLD integrity compared with conventional techniques. Moreover, homogenization of freeze-thawed tissue samples did not induce doxorubicin release, enabling sample cryopreservation prior to analysis. Using this approach, we observed a 3.7-fold higher fraction of unencapsulated doxorubicin relative to total (encapsulated + unencapsulated) concentration in tumors than in liver. This difference may reflect enhanced release and/or prolonged retention of released doxorubicin in tumors, as well as more rapid elimination of released doxorubicin in the liver. Our method is expected to provide critical insights into doxorubicin release from liposomes and the retention of released doxorubicin thereby facilitating the PK/PD and TK/TD analysis of liposomal products. By addressing a fundamental need in liposomal analysis, our method holds significant promise for accelerating drug development and improving cancer therapy outcomes.
Carbon monoxide (CO) is an important modulator of chronic pain, but its clinical use remains limited. To enhance its therapeutic potential, we developed a vesicular CO-releasing system based on a carbonyl metallosurfactant (PCOL6) and soy phosphatidylcholine (SPC) and evaluated its physicochemical properties, as well as its in silico and in vivo effects on inflammation-induced nociception and muscle impairment in male C57BL/6 mice. The metallosomes exhibited a uniform size distribution, stability upon dilution, and a predominantly single membrane, indicating their suitability for therapeutic applications. Computational simulations revealed that PCOL6 can mix with phospholipids to form stable lamellar structures with thinner and more disordered bilayers than those of pure phospholipid membranes. In vivo experiments showed that acute administration of PCOL6/SPC vesicles inhibited complete Freund's adjuvant (CFA)-induced allodynia faster and longer than tricarbonyldichlororuthenium (II) dimer, Ru2Cl4(CO)6 (CORM-2). Repeated metallosome treatment was also more effective than CORM-2 at reducing allodynia, hyperalgesia, and inflammation-related muscle deficits. Both CO releasers normalized CFA-induced NOD-like receptor protein 3 inflammasome overexpression, increased heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 expression, and maintained elevated superoxide dismutase 1 levels in paw tissues; notably, HO-1 induction was greater in PCOL6/SPC-treated mice. These findings suggest that PCOL6/SPC metallosomes represent a promising therapeutic strategy for chronic inflammatory pain.
The co-administration of niclosamide (NCM) with erlotinib hydrochloride (ERL) has been shown to restore ERL sensitivity in resistant non-small cell lung cancer. However, the poor physicochemical properties of both molecules necessitate a specialized delivery system for improved delivery and efficacy. Box-Behnken design was used to evaluate the key variables affecting NCM-ERL-Liposome characteristics. The design yielded a broader design space for the selected factors that can achieve superior attributes, including particle size of 93.42 ± 2.41 nm, polydispersity index of 0.356 ± 0.01, zeta potential of -9.40 ± 0.59 mV, and maximal entrapment efficiencies (NCM: 77.97 ± 2.25%; ERL: 72.75 ± 1.49%). Trehalose showed better redispersion and good physical stability, as confirmed from ATR-IR/PXRD/DSC. The formulation demonstrated sustained dual-drug release, stability for three months at 4 ± 2 °C, and hemocompatibility with minimal hemolysis. In-vitro studies showed that NCM restored ERL sensitivity, with lower IC50 values (HCC827-P: 11.27 ± 4.04 µg/mL; HCC827-ER: 7.59 ± 0.62 µg/mL) than those of pure drugs or the physical mixture. The prepared NCM-ERL-Liposomes showed enhanced internalization, triggered caspase-3/7-mediated apoptosis (1.42-fold increase), and suppressed p-EGFR/p-STAT3, indicating adequate payload protection and targeted intracellular release. These results establish a translational platform that requires PK/PD studies in resistant NSCLC models to support precision oncology therapeutics.
Puerarin (Pue), an isoflavone with diverse pharmacological activities, exhibits poor oral bioavailability due to its low solubility and permeability. To improve its oral delivery, phytosterol ester (PE) was employed as a membrane stabilizer to replace cholesterol (CH) in liposomal formulations. Two Pue-loaded nanoliposomes, CH-Pue-NLs and PE-Pue-NLs, were successfully prepared via ethanol injection. PE-Pue-NLs exhibited a particle size of 219.80 ± 1.81 nm, a zeta potential of 48.76 ± 1.65 mV, and an encapsulation efficiency (EE) of 74.59 ± 1.25%, outperforming CH-Pue-NLs. FTIR and DSC analyses confirmed successful encapsulation of Pue. During 15 days of storage at 4 °C, PE-Pue-NLs showed superior physical stability, maintaining PDI < 0.3, zeta potential > +35 mV, and higher EE (59.42 ± 1.17%) than CH-Pue-NLs, which exhibited marked aggregation and drug leakage. In simulated gastrointestinal fluids, PE-Pue-NLs demonstrated enhanced structural stability and a slower biphasic release profile, with a lower cumulative release in simulated intestinal fluid at 6 h (36.87 ± 1.47%) compared with CH-Pue-NLs (50.29 ± 2.57%). Furthermore, PE-Pue-NLs exhibited reduced binding with mucin and a 1.32-fold higher apparent permeability coefficient (Papp) in Transwell studies, indicating enhanced mucus penetration. In vivo intestinal fluorescence imaging further confirmed improved mucosal permeability of PE-Pue-NLs. These findings suggest that phytosterol ester is a promising alternative to cholesterol for constructing liposomes with improved gastrointestinal stability and intestinal permeability for poorly soluble bioactive compounds.
Carrier-based systems, particularly liposomes, continue to be widely investigated for delivering anticancer treatments. In recent years, multiple approaches have been explored to achieve on-demand delivery of therapeutic cargo from these systems. Here, ultrasound has come to the fore as a practical and precise stimulus to trigger drug release from various formulations. This review explores the interplay between ultrasound and different micro and nanocarriers in oncology, highlighting the mechanisms of ultrasound-triggered delivery, relevance of carrier composition and particle size, cancer types in which the technique holds the most promise, and current barriers and future opportunities related to this approach. We also summarize the existing preclinical studies of US-responsive carriers, with a focus on lipid-based delivery systems. Through the review, the clinical translatability of high-intensity focused ultrasound in drug delivery platform designs is showcased.
Migraine is a chronic neurological disorder that necessitates swift and efficient treatment. Zolmitriptan (ZMT) is a first-line agent with low oral bioavailability and a slow onset of action. Intranasal delivery represents one of the noninvasive routes, directly targeting the nose-to-brain pathway. Therefore, a nano-liposomal system for the co-encapsulation of Zolmitriptan and Ginkgolide B (GB) was developed for efficient intranasal synergistic migraine therapy. The preparation of co-loaded liposomes was performed by thin-film hydration and then optimized by means of DoE. The nanoparticles of the optimal formulation had a mean diameter of 73.13 ± 10.45 nm, high entrapment efficiencies for both ZMT and GB (94.88 ± 2.0% and 95.41 ± 1.3%, respectively) and a biphasic pattern of drug release: a fast burst release of ZMT during the first 2 hours (95.69 ± 4.58%), followed by sustained release of GB within 8 hours (cumulative amount of 98.37 ± 2.87%). The ex vivo permeation study further demonstrated an increased transport across the olfactory mucosa compared to the control treatments. The formulation was well cytocompatible against the nasal cell line (>80% cell viability) and stable upon storage at refrigerated conditions. In this way, it is emphasized that this new dual-drug co-loaded liposomal system may be of great promise in providing improved migraine management through direct brain delivery, but needs in vivo experimentation.
Oral liposome drug delivery system has gained attention due to their potential to improve patient compliance, enhance the bioavailability of encapsulated poorly soluble drugs, and protect drugs from gastrointestinal degradation. Liposomes structurally mimic the human cell membrane, and so are biocompatible and facilitate interactions with cell membranes. However, liposome drug delivery remains inherently challenging due to limitations such as physicochemical instability, limited permeability across GI barriers, and manufacturing scalability constraints. This review first summarizes the current innovative oral liposome products such as Meriva®, Lipicur, and silymarin liposomes. This is followed by a comprehensive overview of the biological barriers for liposome absorption. The report further reviews current understanding the mechanisms for liposomes to cross the GI track and enter the bloodstream, including cellular uptake, transepithelial transport, and lymphatic transport. Formulation strategies to improve absorption such as lipid composition, surface modification techniques such as PEGylation and chitosan are discussed. Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral liposome delivery systems. Finally, the recent development in manufacturing scalability is also covered. Owing to their favorable properties, oral liposome delivery systems remain an active area for innovations in expanding their applications. It is anticipated that demand for oral liposomal drug‑delivery systems will continue to grow, driven by the rising prevalence of chronic diseases that require long‑term therapeutic management.
Berberine (BB) is recognized for its medicinal properties; however, its clinical application is limited by its poor bioavailability. This study prepared ecologically friendly albumin-modified nanobilosomes (ABL) to enhance and compare the therapeutic efficacies of BB and berberrubine (BR) in managing hepatic and renal damages. Hepatic and renal injuries were induced in rats through their daily consumption of toxic metal-contaminated water portion (TM/W) containing lead (20 mg/kg), aluminum (10 mg/kg), and cadmium (5 mg/kg) for 90 days. Rats were subsequently treated with free BB, BR, or BB-ABL/BR-ABL (25 mg/kg/day) for 45 days. Biochemical parameters, oxidative stress, inflammation, and autophagy markers were evaluated. The optimized formulations possessed high drug entrapment efficiencies of 83.2 ± 1.35% for BB-ABL and 84.5 ± 0.06% for BR-ABL. BB-ABL and BR-ABL exhibited significantly greater therapeutic efficacy than free drugs in attenuating TM/W-induced hepatic and renal injuries as evidenced by significant reductions in nitric oxide (NO), microtubule-associated protein light chain 3-II (LC3-II), interleukins (IL-1β and IL-6), and AMP-activated protein kinase (AMPK) protein levels (p < 0.05). Hepatic mTOR levels were significantly elevated by 32.4% and 37.5% in the TM/BB-ABL and TM/BB-ABL treated groups, respectively, while renal mTOR levels increased by 39.6% and 42.8% compared with the TM/W group. Likewise, hepatic PI3K levels increased by 37.9% and 47.4%, whereas renal PI3K levels increased by 33.1% and 37.8% in the TM/BB-ABL and TM/BR-ABL-treated groups, respectively, relative to the TM/W group. Engineered albumin-modified nanobilosomes enhanced the antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulatory properties of BB and BR for the treatment of toxic metal-induced hepatorenal damage.
Liposomes have long been explored as versatile drug delivery systems. Recently, achieving and maintaining asymmetry of liposomes has been the focus of liposomal research. This research aims to provide a novel method for formulating asymmetric liposomes, it focuses on development and optimization of asymmetric liposomes using a cyclodextrin (CD)-lipid exchange method, firstly created by E. London and coworkers, the innovative method has not yet in any publications. The method involves dissolving cyclodextrin in HEPES buffer. The lipid is then dissolved in methanol and added in dropwise approach to cyclodextrin solution. Complexation of the lipid and cyclodextrin is confirmed by several methods involving: infrared spectroscopy which showed shifts of some peaks and disappearance of others, thermogravimetric analysis, differential scanning calorimetry, and nuclear magnetic resonance (the spectra were different compared to the raw materials and physical mixtures). Large unilamellar vesicles (acceptor) are formulating with required lipids via thin film method. Finally, equal volumes of the cyclodextrin-lipid complex and acceptor vesicles suspension are mixed using a shaking water bath (22 °C) for 45mins-1 hour to allow lipid exchange, then asymmetric liposomes, via centrifugation at 15,000RPM at 4 °C for 1 hour, were collected from the rest of vehicle containing the CD-complex on. The asymmetry of liposomes was confirmed by using zetapotential and fluorescence quenching methods. The study showed more stable liposomes compared to those prepared by the conventional method. In future, those asymmetric liposomes prepared by the cyclodextrin-lipid complexation method will be evaluated for their encapsulation efficiency for both small and large drug molecules.
Isoproterenol (ISO), a nonselective β-adrenergic agonist, is widely used to induce myocardial injury and has been reported to cause secondary renal damage known as cardiorenal syndrome, partly driven by oxidative stress and inflammation. Taxifolin (TAX), a flavonoid with potent antioxidant and anti-inflammatory properties, is limited in clinical application due to poor solubility and low bioavailability. This study developed and evaluated chitosan-coated taxifolin liposomes (CS-TL) for the prevention of ISO-induced renal injury in mice. TAX liposomes (TL) were prepared via the ethanol injection method and coated with chitosan to obtain CS-TL. Physicochemical properties, including encapsulation efficiency (EE), particle size, and zeta potential, were characterized. Male mice pretreated with TL or CS-TL received ISO to induce cardiorenal damage. TL exhibited EE of 86.35 ± 3.15%, particle size of 154.8 ± 1.68 nm, and zeta potential of -32.54 ± 3.27 mV, while CS-TL demonstrated EE of 90.70 ± 1.47%, particle size of 289.4 ± 3.27 nm, and zeta potential of +35.26 ± 2.85 mV. ISO induced marked renal tissue damage, increased oxidative stress, inflammatory response, and apoptosis, and suppressed Nrf2/HO-1. Notably, CS-TL pretreatment markedly attenuated ISO-induced alterations in the aforementioned parameters and preserved renal histological architecture. These findings suggest that CS-TL could serve as a promising adjunctive therapeutic strategy for renoprotection in cardiorenal syndromes by ameliorating inflammation, oxidative stress, and apoptosis and restoring the Nrf2/HO-1 cascade.
Breast cancer remains a major health challenge, highlighting the need for more effective and safer therapies. Although doxorubicin is widely used, its clinical utility is limited by oxidative stress-induced toxicity. This study investigated β-carotene and doxorubicin co-delivery in free and liposomal forms using multiple soy lecithin-based formulations. Physicochemical characterization was performed using FTIR spectroscopy, TEM, DLS, zeta potential analysis, and DSC. Biological evaluation was conducted in MCF-7 cells using cytotoxicity assay, apoptosis assay, cell cycle analysis, and comet assay.while cytotoxic selectivity was further assessed by IC50 determination in non-tumorigenic MCF-10A breast epithelial cells. The prepared liposomes showed a uniform spherical morphology, narrow size distribution, and favorable physicochemical stability. Free doxorubicin demonstrated potent anticancer activity against MCF-7 cells (IC50 = 2.46 µg/mL), but was associated with significant apoptosis and DNA damage. liposomal doxorubicin showed moderated cytotoxicity (IC50 = 4.73 µg/mL), consistent with a controlled release profile. Notably, the co-delivery of β-carotene and doxorubicin in liposomes reduced cytotoxic potency (IC50 = 9.98 µg/mL), associated with inducing G2/M cell cycle arrest and apoptosis while reducing genotoxic effects. Liposomal β-carotene and empty liposomes exhibited minimal cytotoxicity. In MCF-10A cells, all liposomal formulations and β-carotene showed negligible toxicity (IC50 > 100 µg/mL), whereas free doxorubicin was highly toxic (IC50 ≈ 5 µg/mL). This toxicity was partially reduced when combined with β-carotene (IC50 ≈ 20 µg/mL). Overall, these findings suggest that liposomal co-delivery of β-carotene and doxorubicin may enhance therapeutic efficacy while potentially reducing off-target toxicity.
Breast cancer (BC) represents a serious threat to public health worldwide, especially for women. Anastrozole (ATZ) is recognized as a therapeutic candidate for treating BC. However, its poor solubility and bioavailability result in low efficacy. This study set out to improve ATZ's ability to manage BC by developing a nasal spray formulation of ATZ-loaded transbilosome (ALT) that would increase ATZ's sustainability, bioavailability, targeting, and efficacy. Design Expert software was used to make different ALT formulations, and the optimum one was chosen. The optimal ALT formulation was then evaluated in vivo using an Ehrlich-induced BC mouse model to assess its efficacy, bioavailability, targeting, and safety. The optimized ALT formulation consists of phospholipid (271.62 mg), Span 60 (24.69 mg), and sodium deoxycholate (18.19 mg). Optimized ALT outperformed free ATZ by 77% in sustainability, 7.88 times in bioavailability, 11.62 times in permeation, and 5.52 times in targeting. Tumor volume, mortality rates, and levels of the biomarkers Ca-15-3 and Ca-27.29 were all significantly lower in the nasal ALT group compared to the disease group by 99.08%, 23.33%, 97.76%, and 98.73%, respectively. The nasal ALT formulation is considered safe because it did not adversely affect kidney or liver functions. In conclusion, the nasal ALT formulation shows potential as a therapy for managing BC.
In this study, we investigated the impact of cationic amphiphilic drugs (CADs) on in vitro and in vivo protein expression following administration of mRNA lipoplexes. The mRNA lipoplexes were formulated using a modified ethanol injection method and applied to human hepatoma HuH-7 cells, human prostate cancer PC-3 cells, and DC2.4 mouse dendritic cells in the presence of various CADs: ebastine (EBS), loperamide (LPM), carvedilol (CVD), nortriptyline (NRT), desloratadine (DSL), and chloroquine (CQ). In vitro, high luciferase (Luc) expression was induced by Luc mRNA lipoplexes in the presence of EBS, LPM, or CVD, whereas similar effects were not observed with NRT, DSL, or CQ. This enhanced expression was attributed to inhibition of lysosomal acidification rather than changes in cellular uptake or mRNA translation efficiency. Intravenous administration of Luc mRNA lipoplexes into the tail vein of mice increased Luc activity in the lungs and spleen; co-administration with EBS or CVD further increased protein expression in the lungs without affecting expression in the spleen. Furthermore, induction of ovalbumin (OVA)-specific antibodies by OVA mRNA lipoplex administration was suppressed by EBS, attributed to reduced TNF-α production in the spleen, whereas CVD did not elicit similar effects. These findings suggest that EBS and CVD promote mRNA lipoplex-mediated protein expression in cultured cells and mouse lung tissue. However, EBS also diminishes antibody responses triggered by mRNA lipoplexes. Accordingly, caution is warranted when administering lipid-based mRNA vaccines to patients taking CADs, as these drugs may influence vaccine efficacy and safety.
Microneedles assisted transdermal delivery of cationic liposomes loaded with selegiline hydrochloride is an innovative approach to treat the symptoms of Parkinson's disease. Previously optimized liposomes of selegiline hydrochloride (SH-LP3) were incorporated within the microneedle array by solvent casting method. The microneedle patch (SH-LP3-MNP) had uniform thickness with an optimum moisture percentage that maintains the mechanical strength of the needle tips. Through an FT-IR study, selegiline and PVA were found to be compatible, showing their prominent functional group. The shape, size, and needle tips of the microneedle were confirmed via SEM analysis. Ex vivo permeability study resembles higher permeation of liposomes through SH-LP3-MNP formulation when compared with SH-MNP. This study also resulted in lower drug retention within the skin membrane. Pharmacokinetic evaluation in Wistar rats indicated that the liposome-loaded microneedles released selegiline in a sustained manner and maintained drug levels in the bloodstream for a longer period, which was reflected by a higher AUC value. The sensory motor coordination of rats improved in microneedle assisted delivery as shown in in vivo antiparkinson disease study. Biochemical tests supported these findings by showing increased antioxidant enzyme activity, reduced lipid peroxidation, and a noticeable rise in dopamine levels in brain tissue. A histopathological study showed improved neuronal regeneration for the SH-LP3-MNP formulation. Through these findings, it was reported that the SH-LP3-MNP formulation is a promising approach for delivering liposomes loaded with selegiline through the skin for the treatment of Parkinson's disease symptoms.
