Current drug delivery最新文献

Background: Cancer treatment often involves the use of potent antineoplastic drugs like Capecitabine (CAP), which can lead to serious toxicities. There is a need for dosage forms to manage these toxicities that can deliver the medication effectively to the target site while maintaining therapeutic efficacy at lower doses. To achieve the aforesaid objective, NLC containing capecitabine (NANOBIN) was prepared and evaluated. Different formulations of NANOBIN, denoted as CaTS, CaT1S, CaT2S, CaTS1, and CaTS2, were designed and evaluated to improve drug delivery and therapeutic outcomes.

Methods: The NANOBIN formulations were prepared using the hot homogenization method. The characterization of these formulations was conducted based on various parameters such as particle size, Polydispersity Index (PDI), Zeta Potential (ZP), Transmission Electron Microscopy (TEM) imaging, and Encapsulation Efficiency (EE). In vitro evaluations included stability testing, release studies to assess drug release kinetics, and a cytotoxicity assay (MTT assay) to evaluate the efficacy of these formulations against human breast cancer cells (MCF-7).

Results: The characterization results revealed that all NANOBIN formulations exhibited particle sizes ranging from 65 to 193 nm, PDI values within the range of 0.26-0.37, ZP values between 46.47 to 61.87 mV (-ve), and high EE percentages ranging from 94.121% to 96.64%. Furthermore, all NANOBIN formulations demonstrated sustained and slow-release profiles of CAP. The MTT assay showed that the NANOBINs exhibited significantly enhanced cytotoxic efficacy, approximately 10 times greater than free CAP when tested on MCF-7 cells. These findings indicate the potential of NANOBINs to deliver CAP effectively to the target site, enabling prolonged drug availability and enhanced therapeutic effects at lower doses.

Conclusion: The study demonstrates that NANOBINs can effectively deliver CAP to target sites, prolonging drug exposure and enhancing therapeutic efficacy while reducing the required dose. Further studies are necessary to validate these findings and establish NANOBINs as a preferred treatment option for cancer therapy.

Pharmaceutical giants (e.g., Ashland, Bausch & Lomb, Johnson & Johnson, Medtronic, Neurelis, etc.) promote the growth of hydrogels globally. Hydrogel-based drug delivery system (DDS) market size accounted for USD 6415 million in 2021 and is estimated to reach USD 12,357 million by 2030, with a compound annual growth rate (CAGR) of 7.6% from 2022 to 2030. Hydrogels, characterized by their unique three-dimensional networks of hydrophilic polymers, have emerged as a keystone in the advancement of biomaterial science. Existing trends in the advancement of hydrogel drug delivery systems (DDS) involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. They excel in their ability to achieve high drug loading capacities, their ease of manufacturing, and their inherent biocompatibility and biodegradability. These attributes not only promise crucial mechanistic features but also offer robust protection for labile drugs and enable the encapsulation of multiple therapeutic agents. Thus, hydrogels stand as promising candidates in various biomedical and pharmaceutical applications, ensuring controlled release and compatibility essential for therapeutic efficacy. Additionally, hydrogels have massive applications in tissue engineering, wound healing, cosmetics, and biomaterials (e.g., contact lenses and implantable devices). Furthermore, hydrogels possess the capability to release active drug(s) under sustained conditions as recommended. Their exceptional qualities position hydrogels as a preferred choice on a global scale. Moreover, they enhance bioavailability, optimize dosage regimens, promote patient compliance, and minimize adverse effects. Furthermore, hydrogels are recommended for use in clinical trials to enhance therapeutic drug delivery outcomes. Despite their remarkable properties, hydrogels do have certain disadvantages, including expensive manufacturing costs and incompatibility with certain drugs. The author has highlighted the fundamental ideas about hydrogels, their classification, global scenario, current developments in the field, and their potential applications. Overall, hydrogel application is progressing rapidly, toward more proficient and effective DDS in the future.

Background: Combining Doxorubicin (DOX) with sorafenib (SF) is a promising strategy for treating Hepatocellular Carcinoma (HCC). However, strict dosage control is required for both drugs, and there is a lack of target selectivity.

Objective: This study aims to develop a novel nano-drug delivery system for the combined use of DOX and SF, aiming to reduce their respective dosages, enhance therapeutic efficacy, and improve target selectivity.

Methods: DOX/SF co-loaded liposomes (LPs) were prepared using the thin-film hydration method. The liposomes were modified with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)- polyethylene glycol (PEG2000), DSPE-PEG1000-cell penetrating peptide TAT, and Glycyrrhetinic Acid (GA). The basic properties of the liposomes were characterized. CCK-8 cell viability assays were conducted using HepG2, MHCC97-H, and PLC cell models, and apoptosis experiments were performed using HepG2 cells to determine if this delivery system could reduce the respective dosages of DOX and SF and enhance HCC cytotoxicity. Liposome uptake experiments were performed using HepG2 cells to validate the target selectivity of this delivery system.

Results: A GA/TAT-DOX/SF-LP liposomal nano drug delivery system was successfully constructed, with a particle size of 150 nm, a zeta potential of -7.9 mV, a DOX encapsulation efficiency of 92%, and an SF encapsulation efficiency of 88.7%. Cellular experiments demonstrated that this delivery system reduced the required dosages of DOX and SF, exhibited stronger cytotoxicity against liver cancer cells, and showed better target selectivity.

Conclusion: A simple and referenceable liposomal nano drug delivery system has been developed for the combined application of DOX and SF in hepatocellular carcinoma treatment.

Introduction: A serious public health condition called liver fibrosis can cause cirrhosis, cancer, and even patient death.

Method: This study sought to determine if Luteolin (LUT) and Silibinin (SBN) could protect rats against oxidative stress and liver fibrosis caused by thioacetamide (TAA) over three weeks, as well as any potential mechanisms of action. There will be 49 adult Wistar albino rats utilized, split up into 7 groups: (G1) Negative control, (G2) Positive control, (G3) LUT+TAA, (G4) SBN+TAA, (G5) mix LUT+ SBN, (G6) LUT+SBN with TAA, (G7) LUT+SBN then TAA, and so. Liver function tests and oxidative stress markers were measured after the experiment. The liver underwent microscopic inspection. Rats given TAA treatment had significantly higher liver enzymes than control; yet, albumin (ALB), total protein (TP), superoxide dismutase (SOD), and reduced glutathione (GSH) significantly decreased.

Results: Following three weeks of TAA exposure, liver sections revealed hepatocytic damage and fibrosis. Oxidative stress, histological alterations, and alterations in liver function were all lessened in TAA rats administered with LUT, SBN, or both.

Conclusion: The combined hepatoprotective benefits of LUT and SBN prevented TAA-induced biochemical and histological alterations in rat liver, acting in concert with each other.

Small nucleic acids (sNA) are revolutionizing several therapeutic environments in areas such as oncology as well as rare disease states. However, despite the progress in RNA modification, lipid nanoparticles (LNPs), and GalNAc conjugation methods, issues like toxicity, immunogenicity, and stability limitations affect the application. Compared with viral and non-viral systems, LNPs have become more credible carriers to solve the problems of RNA degradation and realize more innovation, such as the first RNA interference drug, Patisiran. Likewise, methods for GalNAc conjugation have enabled liver-targeting therapies with better pharmacokinetic profiles. Relative to this subject, novel strategies such as exosome-mediated delivery and multifaceted systems involving LNP-GalNAc and exosome all hold more specificity and biostability. Some of the recent advancements in RNA chemical modifications involve the application of 1-methylpseudouridine which enhances the stability of the RNA and also reduces its immunogenic outcomes. Also, the application of AI in therapeutic areas includes establishing the delivery vectors, estimating severe side effects, and designing new nucleic acid therapies. In addition to hepatic targeting, tissue targetability is now being investigated for other purposes. A solution to the existing stability and targeting limitations is critical for the further development and enhanced use of sNA therapies in broad diseases, including chronic and complex diseases. The major focus of this review is on the recent development and potential future trends of sNA as a drug delivery system for precision medicine.

Objective: This study aimed to develop an emulgel containing minoxidil as a drug for hair growth promotion in diseases, such as androgenetic alopecia, using gelling agents, such as chitosan and fucoidan.

Methods: In this study, gelling agents were selected for the emulgel formulation. By various evaluation tests and through optimization, the chitosan-fucoidan combination was selected as the gelling agent for the preparation of emulgel using various evaluation parameters.

Results: X2, the best emulgel formulation, contained 2.54 % chitosan and 0.896 % fucoidan. Chitosan prolonged the duration of drug release, and controlled release was obtained. Fucoidan increased the gelling activity, water absorption rate, and stability of the formulation. In this study, the X2 formulation showed the highest percentage of drug release at the 12th hour. It was found to be 99.7%, which followed the zero-order release model.

Conclusion: Owing to the wide range of biological activities of fucoidan, the loaded active substance can be protected, and at the same time, its potency can be improved, resulting in effective treatment. Because fucoidan has diverse properties and potential, it will be widely used in the biomedical and pharmaceutical industries in the future.

Introduction/background: Tetrandrine (TET) has multiple pharmacological activities, but its water solubility is poor, which is the main reason for its low bioavailability.

Objectives: The purpose of this study was to prepare TET nanocrystals (TET-NCs) using a grinding method to enhance the dissolution rate and ultimately improve the bioavailability of TET.

Methods: TET-NCs were synthesized via media milling, employing Poloxam 407 (P407) as surface stabilizer and mannitol as a cryoprotectant during freeze-drying. The crystal structure, particle diameter, and zeta potential were characterized using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The in vitro release behavior and pharmacokinetics of TET-NCs were assessed. The cytotoxicity of TET and TET-NCS on RAW264.7 cells was determined by the CCK-8 method.

Results: The particle size of TET-NCs was 360.0±7.03 nm, PDI was 0.26±0.03, and zeta potential was 6.64±0.22 mV. The cumulative dissolution within 60 minutes was 96.40±2.31%. The pharmacokinetic study showed that AUC0-72 h and Cmax of TET-NCs were significantly enhanced by 3.07 and 2.57 times, respectively, compared with TET (p<0.01). TET-NCs significantly increased the cell inhibition on RAW264.7 cells compared to the TET (P<0.01).

Conclusion: The preparation of TET-NCs enhanced dissolution rate and bioavailability significantly, and it also improved the inhibition effect of RAW264.7 cells.

Background: Plant-derived extracellular vesicles (PDEVs) are vital for intercellular material exchange and information transfer. They significantly regulate cellular functions, tissue repair, and self-defense mechanisms.

Objective: This review summarizes the formation pathways, composition, and potential applications of PDEVs in anti-tumor research and drug delivery systems.

Methods: We conducted a literature search using keywords such as "plant-derived extracellular vesicles," "exosomes," "drug delivery," "isolation and purification," "stability," "anti-tumor," and "tumor therapy" in databases including PubMed, Web of Science, and Scopus. We examined studies on the formation pathways of PDEVs, including fusion of multivesicular bodies with the plasma membrane, exosome-positive organelles, and vacuole release. We also reviewed isolation and purification techniques critical for studying their biological functions. Furthermore, we analyzed research on the application of PDEVs in cancer therapy, focusing on their inhibitory effects in various cancer models and their role as carriers in drug delivery systems.

Results: PDEVs have demonstrated potential in anti-tumor research, particularly with vesicles from plants like tea, garlic, and Artemisia annua showing inhibitory effects in breast, lung, and gastric cancer models. Additionally, PDEVs serve as effective carriers in drug delivery systems, offering possibilities for developing ideal therapeutic solutions.

Conclusion: While PDEVs show promise in cancer treatment and drug delivery, challenges such as standardization, storage stability, and elucidation of action mechanisms remain. Further research is needed to overcome these challenges and advance the clinical translation of PDEVs.

Introduction: Exosomes are nanoscale extracellular vesicles that widely participate in intercellular communication. An increasing number of studies have reported on the neuroprotective effects of stem cell-derived exosomes in brain diseases through various delivery methods. However, only a few reports are available on the delivery and uptake of stem cell-derived exosomes in the brains of mice of different ages.

Methods: PKH-26-labelled mesenchymal stem cell-derived exosomes were collected, and their uptake was investigated in the brains of mice aged 2 weeks, 2 months, and >6 months, 24 hours after intranasal delivery.

Results: No exosomes were distributed in the whole brains of 2-week-old mice after 24 hours of intranasal delivery. However, a small number of exosomes were found in the olfactory bulb, cortex, and hippocampus of 2-month-old mice, with no exosomes observed in the cerebellum. In contrast, a large number of exosomes were ingested in all brain regions, including the olfactory bulb, cortex, hippocampus, and cerebellum, of >6-month-old mice.

Conclusion: Exosomes can enter the brains of adult mice through intranasal administration, but there are differences in the uptake rate among mice of different ages. These findings provide a theoretical basis for the future clinical administration of exosomes for treating brain disorders.