Pharmaceutics最新文献

Background/Objectives: Bacteria are becoming increasingly resistant to levofloxacin and other fluoroquinolones. Previously, drug loading in colloidal carriers has shown enhanced penetration into and retention in bacterial cells. However, the mechanism of levofloxacin niosomes' bio-disposition in rats has not been reported. This study investigated the pharmacokinetics (PK) of optimized levofloxacin niosomes following intraperitoneal injection into Sprague Dawley rats. Methods: Formulation and processing variables settings were determined using DoE Fusion One software. The resulting data input into the Optimizer module provided niosome formulation for in vivo study in Sprague Dawley rats. Each group of rats (n = 6) was injected intraperitoneally with either conventional levofloxacin or its niosomes at equivalent doses of 7.5 mg/kg/dose. Blood samples were collected via tail snip and analyzed using a validated HPLC method. The plasma-time data were fed into the Gastroplus software (Simulations Plus, CA) and used to model levofloxacin PK. Results: Niosomes for in vivo study had a mean hydrodynamic diameter of 329.16 nm (±18.0), encapsulation efficiency (EE) of 30.74%, Zeta potential of 21.72 (±0.54), and polydispersity index (PDI) of 0.286 (±0.014). Both the Akaike and Schwarz criteria showed levofloxacin niosomes and conventional drug formulation obeying one- and two-compartment PK models, respectively. Thus, formulation in niosomes altered levofloxacin biodistribution by concentrating the drug in the vascular compartment. Conclusions: Niosome encapsulation of levofloxacin altered its biodistribution and pharmacokinetic profile, possibly by protecting i.p. levofloxacin en route into plasma, and significantly enhanced its plasma concentration with enhanced potential for treating intravascular infections.

Liposome-based targeted drug delivery systems represent a significant advancement in pharmaceutical science, offering distinct advantages that enhance the efficacy and safety of various therapies. These versatile carriers can encapsulate both hydrophilic and hydrophobic drugs, making them particularly valuable in clinical settings. This review explores the critical role of liposomal formulations in improving drug pharmacokinetics and minimizing side effects, especially in oncology, where targeted delivery to tumor cells is essential. Outlining the properties of different types of liposomes, we focus on the effects of these properties on the liposomes' targeting and drug release capabilities through innovative surface modifications and describe the most common methods of liposome preparation and characterization. Furthermore, this review provides an in-depth analysis of the properties and composition of liposomal-based nanocarriers, with a unique focus on ongoing clinical trials and recently approved therapies. It offers a comprehensive overview of the latest advancements in pre-clinical research and highlights the critical progress in clinical development, offering insights into the clinical impact and regulatory approvals. Ultimately, this review underscores the transformative potential of liposomal nanocarriers in modern therapeutics, suggesting avenues for future innovations and clinical breakthroughs.

Background: Oral lichen planus (OLP) is a chronic autoimmune disease of the oral mucosa, classified among potentially malignant oral disorders (OPMDs). It is characterized by keratinocyte apoptosis and persistent inflammation. Standard treatments involve topical corticosteroids administered via mouthwashes, gels, or ointments, but these require frequent application, have limited retention, and may cause side effects. To address these limitations, this study aimed to develop an innovative dexamethasone delivery system targeting the oral cavity, based on poly(lactic acid) (PLA) fibers coated with chitosan (CS) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Methods: CS-coated PLA fibers were characterized for their mucoadhesive and cytocompatibility properties, while PLGA nanoparticles were analyzed for size, shape, encapsulation efficiency, cellular uptake, drug release efficiency, and cytocompatibility. Results: Both polymers demonstrated cytocompatibility, and chitosan-coated PLA fibers exhibited mucoadhesive properties. PLGA nanoparticles were effectively internalized by the cells and successfully released the drug into the cytoplasm. The combination of CS-coated PLA fibers and PLGA nanoparticles provided dual benefits: mucoadhesion and efficient cellular uptake, even under conditions simulating salivation. Conclusions: These findings highlight the potential of the proposed system to improve mucoadhesive drug delivery. Further optimization is needed to enhance patient compliance and therapeutic efficacy.

Background/Objectives: This study explored the antitumor effect of Passiflora incarnata leaves' nanoformulation (N-EEP) in fibroblasts, A375 cell lines, and in vivo using Dalton's lymphoma ascites (DLA)-bearing mice. Methods: N-EEP treatment could significantly slow scratch closing in A375 cells compared to in the extract itself (EEP). Results: The hemolytic assay showed that N-EEP had less than 2% hemolysis, making the formulation highly biocompatible. In vivo N-EEP administration delayed the tumor growth rate, reduced weight gain, and increased the tumor-bearing mice's life span. Furthermore, the ascitic cells were aspirated from the tumor and investigated for various gene expressions. The tumor suppressor gene p53, which plays a significant role in the mitochondrial-mediated apoptosis pathway, was found to be elevated in animals treated with N-EEP. We assessed the cytotoxicity of isolated DLA cells from induced mice using both the trypan blue and MTT assays, while apoptotic studies were conducted using Hoechst staining. Results from the trypan blue and MTT assays indicated that nearly 80% of the cells were killed by N-EEP treatment (200 μg/mL). Additionally, apoptosis, characterized by condensed nuclei, was observed after N-EEP treatment, confirming that one of the modes of cell death was caspase-dependent apoptosis. Conclusions: Our study suggests that N-EEP delayed the growth of DLA by upregulating p53 gene expression and inducing apoptosis.

Objectives: Ultrafiltration (UF) is widely accepted as a method for assessing the plasma protein binding (PPB) of drugs. However, it is vulnerable to non-specific binding (NSB) to the device, which can result in inaccuracies. This study presents a straightforward, high-throughput modified UF method aimed at minimizing bias due to NSB. Methods: The modified UF method, sequential UF, features the addition of a 2 min pre-UF phase designed to saturate the NSB in the device, followed by the main 20 min UF procedure, compared to the conventional UF method. To evaluate the feasibility of this sequential UF method, we measured the PPB of nine compounds using sequential UF and compared these results to those obtained with the conventional mass balance UF method, recognized as a standard for NSB correction. Results: The PPB values determined through sequential UF were generally consistent with those derived from the mass balance UF method. The fold differences ranged from 97.9% to 113.8%, with an average of 103.5%. No significant differences were observed between the two methods for all compounds, with the exception of quercetin, which showed an unusually high PPB. Conclusions: Sequential UF was effective in correcting NSB to the device while providing advantages in terms of simplicity and efficiency.

Objectives: This study aimed to evaluate the effectiveness of gonadotropin-releasing hormone-loaded chitosan-TPP nanoparticles (GnRH-CNPs) and prostaglandin F_2α-loaded chitosan-TPP nanoparticles (PGF_2α-CNPs) within the Ovsynch protocol for enhancing reproductive performance in heat-stressed dairy cows. Methods: Thirty-six cyclic purebred Friesian cows not detected in standing heat for more than 90 days postpartum were randomly allocated to three treatment groups. The control group (OVS, n = 12) followed the standard Ovsynch protocol with conventional doses. The ½ OVS group (n = 12) received 5 µg GnRH-CNPs on days 0 and 9, along with 250 µg PGF_2α-CNPs on day 7. While the ¼ OVS group (n = 12) was administered 2.5 µg GnRH-CNPs on days 0 and 9, with 125 µg PGF_2α-CNPs on day 7. Ovarian follicular dynamics and corpus luteum (CL) development were monitored on days 0, 4, 7, and 9 of the protocol. Serum progesterone (P₄) concentrations were measured throughout the synchronization period and on days 15 and 30 post-AI. Pregnancy was diagnosed on day 30 post-AI. Results: The ¼ OVS protocol achieved a significantly greater follicular response (p < 0.05) than other protocols. On day 4, following the first GnRH administration, the OVS group exhibited a higher number of subordinate follicles (p < 0.05) and a greater diameter of the dominant follicles (DFs), whereas the ¼ OVS group showed a greater subordinate follicle diameter (p < 0.05) and a higher number of DFs. On day 9, after PGF_2α administration, the ¼ OVS group maintained an elevated number of subordinate follicles, while larger subordinate follicle diameters were observed in the ½ OVS and OVS groups. No significant differences in DF numbers and diameters were observed among groups. P₄ concentrations remained similar across groups during treatments. Compared to control, a significantly higher value of P₄ concentration (p < 0.05) was recorded on day 15 post-AI in the ½ OVS group and on day 30 post-AI in the ¼ OVS group. These findings correlated with a higher pregnancy rate in the ¼ OVS group (65%) compared to the ½ OVS and OVS groups (40% in each). Conclusions: Nanofabrication reduced GnRH and PGF_2α dosage by 50% and 75% without impairing ovarian response and pregnancy rates. The ¼ OVS protocol notably enhanced the ovarian activity and fertility, highlighting the use of GnRH-CNPs and PGF_2α-CNPs as promising and practical approaches to enhance the fertility in dairy cattle under heat stress (HS).

Background: On-demand personalized drug production is currently not addressed with large-scale drug manufacturing. In our study, we focused primarily on identifying possible active pharmaceutical ingredients (APIs) for 3D Printing (3DP) in the current healthcare setting. Methods: We conducted a retrospective cross-sectional study in the Netherlands using three different sources; community pharmacies (n = 5), elderly care homes (n = 3), and the Erasmus MC Sophia Children's Hospital. The primary endpoint was the percentage of prescriptions of medication manipulated before administration, thereby being a candidate for 3DP. Around a million prescriptions were analyzed in our study. Results: This study shows that around 3.0% of the prescribed drugs dispensed by Dutch community pharmacies were manipulated before administration, while around 10.5% of the prescribed drugs in the Erasmus MC Sophia Children's Hospital were manipulated prior to administration. Conclusions: With our study, we show that the most manipulated drugs come from the groups of constipation, psychopharmaceutical, cardiovascular, and anti-infectant drugs. Successful introduction of a compounded API drug by 3DP does not only rely on the API, but it also comes with an optimal balance between technical, economic as well as societal impact factors. Our study gives direction for potential future research on the introduction of 3DP of medicine in the healthcare setting.

Background and Aim: Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary atresia is not yet fully understood. Nuclear factor-κB (NF-κB) is widely acknowledged as a key regulator in the pathogenesis of hepatitis and liver fibrosis, and extensive research has been conducted to develop strategies to effectively inhibit its activity to mitigate liver damage. Exosome-based therapeutic platforms offer targeted NF-κB inhibition with low immunogenicity and enhanced liver-specific delivery. This study aimed to evaluate the therapeutic efficacy of Exo-SrIκB in treating cholestatic liver fibrosis using experimental animal models. Methods: Exo-SrIκB (an exosome-based therapy containing the super-repressor IκB protein) using EXPLOR technology (Exosome engineering for Protein Loading via Optically Reversible protein-protein interactions) to encapsulate the super repressor IκB (SrIκB) within exosomes. The therapeutic efficacy of Exo-SrIκB was assessed in minipig and mouse models with experimentally induced cholestatic liver disease. Results: Administration of Exo-SrIκB significantly attenuated liver fibrosis progression in both animal models by inhibiting NF-κB nuclear translocation and reducing the expression of fibrotic markers. Treated animals exhibited reduced collagen deposition, lower α-SMA levels, and improved hepatic function compared to untreated controls. Conclusion: Exo-SrIκB effectively suppressed NF-κB signaling and alleviated liver fibrosis in experimental cholestatic liver disease models, suggesting that exosome-based therapeutics may offer a targeted and biocompatible application to managing liver fibrosis and other chronic liver diseases.

Objectives: This study evaluated the potential of sustainably sourced, plant-based homopolymers derived from citronellol as an alternative to the traditional emollients used in pharmaceutical, cosmetic, and personal care products. With increasing emphasis on environmentally friendly ingredients and manufacturing processes, this study assessed the efficacy of these homopolymers in semi-solid and emulsion-based formulations. Methods: The analyses focused on physicochemical, sensory, biophysical, and neurosensory characteristics. Results: The results demonstrated that emulsions containing sustainable homopolymers maintained viscoelastic stability, preserving rheological properties over time under varying conditions. These formulations showed comparable structural and functional stability to those with traditional emollients while offering skin hydration, moisture retention, and elasticity, with reduced transepidermal water loss. Sensory evaluations highlighted positive user acceptance, with participants favoring the skin feel and in-use qualities of these emulsions over synthetic alternatives. Neurosensory analyses confirmed the strong visual appeal of the product packaging, capturing user attention effectively. Conclusions: These findings underline the capability of plant-based homopolymers to replace traditional emollients while providing significant consumer appeal and sustainability benefits. This study establishes their potential as viable components in the development of more eco-friendly topical formulations for the pharmaceutical, cosmetic, and personal care industries.

Background/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood-brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the "molecular Trojan horse" technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1-4) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1-42 peptide, we established an in vitro Alzheimer's disease (AD) model. In this model, the potential usability of MP1-4 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes' particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% ± 2.7%), controlled release (72 h release: 38.5% ± 1.2%), and stable morphology (PDI: 0.22 ± 0.03, zeta potential: -31.4 ± 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p < 0.05) in the presence of Aβ1-42 at a concentration of 47 µg/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer's disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications.