Pharmaceutics最新文献

Background/Objectives: The development of polymer-lipid hybrid nanoparticles (PLNs) is a promising area of research, as it can help increase the stability of cationic lipid carriers. Hybrid PLNs are core-shell nanoparticle structures that combine the advantages of both polymer nanoparticles and liposomes, especially in terms of their physical stability and biocompatibility. Natural polymers such as polyhydroxyalkanoate (PHA) can be used as a matrix for the PLNs' preparation. Methods: In this study, we first obtained stable cationic hybrid PLNs using a cationic liposome (CL) composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride), helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), and the hydrophobic polymer mcl-PHA, which was produced by the soil bacterium Pseudomonas helmantisensis P1. Results: The new polymer-lipid carriers effectively encapsulated and delivered model mRNA-eGFP (enhanced green fluorescent protein mRNA) to BHK-21 cells. We then evaluated the role of mcl-PHA in increasing the stability of cationic PLNs in ionic solutions using dynamic light scattering data, electrophoretic mobility, and transmission electron microscopy techniques. Conclusions: The results showed that increasing the concentration of PBS (phosphate buffered saline) led to a decrease in the stability of the CLs. At high concentrations of PBS, the CLs aggregate. In contrast, the presence of isotonic PBS did not result in the aggregation of PLNs, and the particles remained stable for 120 h when stored at +4 °C. The obtained results show that PLNs hold promise for further in vivo studies on nucleic acid delivery.

Background/objectives: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models.

Methods: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started.

Results: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design.

Conclusions: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models.

Biomimetic nanoparticles (BMNPs) are innovative nanovehicles that replicate the properties of naturally occurring extracellular vesicles, facilitating highly efficient drug delivery across biological barriers to target organs and tissues while ensuring maximal biocompatibility and minimal-to-no toxicity. BMNPs can be utilized for the delivery of therapeutic payloads and for imparting novel properties to other nanotechnologies based on organic and inorganic materials. The application of specifically modified biological membranes for coating organic and inorganic nanoparticles has the potential to enhance their therapeutic efficacy and biocompatibility, presenting a promising pathway for the advancement of drug delivery technologies. This manuscript is grounded in the fundamentals of biomimetic technologies, offering a comprehensive overview and analytical perspective on the preparation and functionalization of BMNPs, which include cell membrane-coated nanoparticles (CMCNPs), artificial cell-derived vesicles (ACDVs), and fully synthetic vesicles (fSVs). This review examines both "top-down" and "bottom-up" approaches for nanoparticle preparation, with a particular focus on techniques such as cell membrane coating, cargo loading, and microfluidic fabrication. Additionally, it addresses the technological challenges and potential solutions associated with the large-scale production and clinical application of BMNPs and related technologies.

Background: Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; Methods: In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; Results: DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; Conclusions: These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy.

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV-vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025-0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation.

Objective: This study aimed to investigate the feasibility of using the digital image processing technique, developed to semi-quantitatively study dermal penetration, to study corneal penetration in an ex vivo porcine eye model. Here, we investigated various formulation strategies intended to enhance dermal and corneal bioavailability of the model hydrophobic drug, curcumin.

Methods: Several formulation principles were explored, including oily solutions, oily suspensions, aqueous nanosuspension, micelles, liposomes and cyclodextrins. The dermal penetration efficacy was tested using an ex vivo porcine ear model previously developed at Philipps-Universität Marburg with subsequent digital image processing. This image analysis method was further applied to study corneal penetration using an ex vivo porcine whole-eye model.

Results: For dermal penetration, oily solutions, oily suspensions and nanosuspensions exhibited the least penetration, whereas liposomes and cyclodextrins showed enhanced penetration. Corneal curcumin penetration correlated with dermal penetration, with curcumin loaded into cyclodextrins penetrating the deepest.

Conclusions: Overall, our study suggests that the image analysis method previously developed for ex vivo skin penetration can easily be repurposed to study corneal penetration of hydrophobic drugs.

Background/objectives: Phloroglucinol (PHL), a phenolic compound extracted from the brown alga Rosenvingea intricata, exhibits potent antioxidant and anticancer properties. This study aims to extract, purify, and characterize PHL, and further develop functionalized zinc oxide nanoparticles (ZnO NPs) loaded with PHL to enhance its therapeutic potential.

Methods: PHL was extracted using acetone and purified through Sephadex LH-20 column chromatography, yielding a highly enriched fraction (F-3). The purified compound was characterized by FTIR, HPLC, NMR, and LC-MS. ZnO NPs were synthesized, PEGylated, and conjugated with PHL, forming ZnO-PEG-PHL NPs. Their characterization included DLS, zeta potential, XRD, SEM-EDAX, and encapsulation efficiency studies. Antioxidant assays (DPPH, FRAP, ABTS, RPA) were performed and in vitro cytotoxicity on A549 lung cancer cells were determined to evaluate the therapeutic efficacy of PHL.

Results: The purified PHL fraction showed a high phenolic content (45.65 PHL mg/g), which was was confirmed by spectral analysis. The ZnO-PEG-PHL NPs increased in size from 32.36 nm to 46.68 nm, with their zeta potential shifting from -37.87 mV to -26.82 mV. The antioxidant activity was superior for the ZnO-PEG-PHL NPs in all assays, while the in vitro cytotoxicity tests showed an IC₅₀ of 40 µg/mL compared to 60 µg/mL for the ZnO NPs and 70 µg/mL for PHL. Apoptotic studies revealed significant cell cycle arrest and apoptosis induction.

Conclusions: The synthesized ZnO-PEG-PHL NPs demonstrated enhanced antioxidant and anticancer properties, making them promising candidates for cancer therapy and antioxidant applications.

Background/Objectives: Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are leading causes of vision loss, with AMD affecting older populations and RP being a rarer, genetically inherited condition. Both diseases result in progressive retinal degeneration, for which current treatments remain inadequate in advanced stages. This review aims to provide an overview of the retina's anatomy and physiology, elucidate the pathophysiology of AMD and RP, and evaluate emerging cell-based therapies for these conditions. Methods: A comprehensive review of the literature was conducted, focusing on cell therapy approaches, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells. Preclinical and clinical studies were analyzed to assess therapeutic potential, with attention to mechanisms such as cell replacement, neuroprotection, and paracrine effects. Relevant challenges, including ethical concerns and clinical translation, were also explored. Results: Cell-based therapies demonstrate potential for restoring retinal function and slowing disease progression through mechanisms like neuroprotection and cell replacement. Preclinical trials show promising outcomes, but clinical studies face significant hurdles, including challenges in cell delivery and long-term efficacy. Combination therapies integrating gene editing and biomaterials offer potential future advancements. Conclusions: While cell-based therapies for AMD and RP have made significant progress, substantial barriers to clinical application remain. Further research is essential to overcome these obstacles, improve delivery methods, and ensure the safe and effective translation of these therapies into clinical practice.

Background/objectives: Considering the antioxidant and antimicrobial properties attributed to compounds in Syzygium cumini extract, this research aimed to advance postoperative therapeutic innovations. Specifically, the study assessed the physicochemical properties of a film-forming solution (FFS) incorporated with S. cumini, evaluating its therapeutic potential for postoperative applications.

Methods: The S. cumini extract was meticulously characterized to determine its chemical composition, with particular emphasis on the concentration of phenolic compounds. Antioxidant and antimicrobial assays were conducted to assess the extract's efficacy in these domains. Following this, an FFS containing S. cumini was formulated and evaluated comprehensively for skin adhesion, mechanical and barrier properties, and thermal behavior.

Results: The antioxidant and antimicrobial activities of the S. cumini extract demonstrated promising results, indicating its potential utility as an adjunct in postoperative care. The developed FFS exhibited favorable physicochemical properties for topical application, including adequate skin adhesion and appropriate pH levels. Moreover, chemical and thermal analyses confirmed the formulation's stability and the retention of the extract's beneficial properties.

Conclusions: Overall, the findings suggest that the S. cumini-loaded FFS holds significant potential as a valuable therapeutic tool for post-surgical management.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT_1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.