Current drug delivery最新文献

Introduction: Renal fibrosis is widely recognized as the final common pathway in chronic kidney disease (CKD) progression, culminating in end-stage renal failure, and is characterized by excessive extracellular matrix (ECM) accumulation by renal myofibroblasts within the renal interstitium, ultimately leading to functional decline. In this study, to establish an effective drug delivery system targeting fibrotic lesions in the renal interstitium, we developed nanoparticles modified with short-chain peptides that bind type IV collagen (Col IV), a distinct ECM component predominantly remodeled in fibrosis.

Methods: Col IV-targeting nanoparticles were intravenously administered to a unilateral ureteral obstruction (UUO) rat model of renal fibrosis. The distribution of these nanoparticles to the renal interstitium was examined via fluorescence-based ex vivo imaging and analysis of frozen kidney tissue sections. Additionally, we assessed cellular uptake in renal fibroblasts (NRK-49F), with or without transforming growth factor-beta 1 (TGF-β1) stimulation, using flow cytometry.

Results: Both Col IV-targeting and non-targeting nanoparticles exhibited increased distribution in the fibrotic renal interstitium compared to healthy renal tissue. Moreover, the Col IV-targeting nanoparticles localized more extensively in the fibrotic interstitium than their non-targeting counterparts. In vitro, Col IV-targeting nanoparticles also showed significantly higher accumulation in NRK-49F cells, irrespective of TGF-β1 stimulation, compared to non-targeting nanoparticles.

Conclusion: We successfully fabricated and evaluated Col IV-targeting nanoparticles as a potential drug delivery platform. In a UUO-induced renal fibrosis model, these nanoparticles efficiently migrated to the fibrotic renal interstitium, and in vitro experiments using NRK-49F cells demonstrated enhanced uptake by renal fibroblasts and myofibroblasts, central mediators of ECM deposition in fibrotic progression. These findings suggest that Col IV-targeting nanoparticles may serve as an effective drug carrier for delivering antifibrotic therapies, potentially mitigating CKD progression.

With the continuous development of material science, many new biomaterials have emerged. Peptides have a strong supramolecular self-assembly ability and can form hydrogels through a self-assembly process. These self-assembled peptide hydrogels have the advantages of excellent biocompatibility, tunability, and degradability, and are suitable for biomedical fields. This paper reviews the mechanisms and characteristics of peptide gel formation, outlines the various factors affecting peptide gelation, and the applications of peptide hydrogels in drug delivery, tissue engineering, and wound healing. Finally, challenges encountered in self-assembled peptide gels and prospects for their application are highlighted.

Electrospun scaffolds are pivotal in tissue engineering due to their ability to mimic the Extracellular Matrix (ECM). Despite their potential, challenges such as, two-dimensional structure, limited load bearing capacity, and low mechanical strength restrict their application. This review explores advancements in electrospinning techniques and materials, highlighting methods like coaxial electrospinning, which enables the encapsulation of therapeutic agents, and the integration with 3D printing to create hybrid scaffolds with improved cell infiltration. Characterization techniques assessed by different researchers, such as scaffold morphology, mechanical properties, and biocompatibility, show that scaffolds with high spatial interconnectivity and controlled alignment enhance cell orientation and migration. Innovations in smart polymers and stimuli-responsive materials have furthered scaffold functionality. While recent advancements address some limitations, issues with scalability and production uniformity remain. Future research should optimize fabrication parameters and explore novel materials to enhance scaffold performance, requiring collaborative efforts and technological innovations to expand their practical applications in tissue engineering and regenerative medicine.

4D printing is an improvement over the traditional 3D printing technique involving the application of dynamic materials that change with the environmental conditions, including temperature, humidity, and pH. This technology holds great promise for drug development to create effective and personalized drug delivery systems. Different from conventional technologies, 4D printed systems can control the administration rate of drugs depending on the internal environment, thus enhancing the effectiveness of treatments and considering adverse effects at the same time effectively. 4D printing contributes to the creation of smart materials for use in vaccines, implants, and other devices that respond to body signals in real-time. However, several hurdles persist in the synthesis and fabrication of these materials as well as their regulatory approval. This technology represents the future of drug manufacturing, emphasizing patient-specific care and providing a more effective, efficient, and adaptive approach to therapeutic delivery.

Background: The interaction of the kidneys with nanoparticles is a fundamental issue that accelerates the proper design of efficient and safe nanotherapeutics. The present study aimed to establish the kidney toxicity and the biodistribution profile of novel gold and silver nanocluster formulations.

Methods: Gold and silver nanoclusters were synthesized in an albumin template to probe their kidney- nano interaction. The interaction was performed on healthy animals to unveil the toxicity of nanoclusters on kidney tissue.

Results: Albumin-based gold nanoclusters (BSA-AuNCs) and albumin-based silver nanoclusters (BSA-AgNCs), exhibited comparable core size (2.2±1.3 nm and 2.5±1.6 nm, respectively) and hydrodynamic diameter (11.3±2.1 nm for BSA-AuNC and 10.7±1.9 nm for BSA-AgNC) indicating similarity in their core and overall sizes. Zeta potential measurements demonstrated a comparable surface charge between BSA- AuNC (18.1±3.2 mV) and BSA- AgNC (20.1±3.6 mV), which closely resembled the surface charge of albumin in water (20.7±3.5 mV). Upon administration to rats via intravenous route, ICP-OES measurements showed a significant silver and gold nanocluster accumulation in various vital organs with unequal distribution patterns. BSA-AgNC exhibited higher concentrations in the liver and spleen, while BSA-AuNC showed predominant accumulation in the liver and kidneys. However, the administered BSA-AgNC induced more renal damage than BSA- AuNCs.

Conclusion: The identified renal toxicity linked to BSA-AgNCs, despite their lower kidney accumulation than BSA-AuNCs, illuminates the intricate interplay between nanoparticle biodistribution and toxicity. This underscores the significance of considering the core metal type in nanoparticle design and evaluation. Further investigation is needed to clarify the underlying molecular mechanisms of the observed biodistribution and toxicity.

As colorectal cancer is the third most common cancer globally, this study aimed to improve colorectal cancer treatment using nanostructured lipid carriers (NLCs) for drug delivery by overcoming the current drawbacks, improving therapeutic effectiveness, achieving site-specific delivery, and implementing controlled drug administration to mitigate systemic side effects. Based on the literature, it has been observed that the optimal drug size and zeta potential range depend on the drug formulation's targets and features. These ranges are determined through optimization and characterization. The particle size ranges from 10 to 200 manometers, and the zeta potential values range from -30 mV to +30 mV. Optimal formulations should have uniform spherical morphology and compatibility with biological entities. This paper provides an in-depth analysis of nanocarrier research and findings. This article offers a thorough synopsis of the latest research and findings on nanocarriers, offering a valuable understanding of their development.

Introduction: There is a strong need for drug delivery systems that are both highly compatible with biological tissues and effective when used in the oral mucosa. While gels, creams, or ointments are currently employed for this purpose, their oral bioavailability is constrained by the limited contact time with mucosal tissue.

Method: In response to this challenge, we developed and evaluated the efficacy of a multilayer mucoadhesive system incorporated with Dexamethasone Sodium Phosphate (DEX-P) for oral mucosal delivery. An electrospun multilayer system was created and subjected to biocompatibility and efficiency testing through both in vitro and ex vivo approaches, finally culminating in an acceptability trial in healthy human volunteers. The multilayer system was created using Poly-Vinyl Pyrrolidone (PVP) and Poly ε-Caprolactone (PCL) as a polymeric base and Polycarbophil (NOVEON® AA-1, PCF) serving as an adhesion enhancer to facilitate the unidirectional release of Dexamethasone Sodium Phosphate (DEX-P).

Result: The nanofibers matrices underwent morphological characterization by Scanning Electron Microscopy (SEM), and DEX-P release was evaluated using ex vivo porcine mucosa, yielding promising results. In vitro cytotoxicity was evaluated through the MTT assay, employing HFF-1 cells. The cell viability ranged from 78 to 96%, suggesting the safety of the polymers used. The tested dose range of DEX on cell lines did not decrease below 75%, indicating its safety in terms of in vivo cytotoxicity. Biocompatibility was evaluated on animal models, with no considerable tissue damage observed.

Conclusion: Human in vivo studies demonstrated prolonged adhesion and a favorable perception of the system.

A revolutionary encapsulation-based drug delivery technique called novasome technology outperforms conventional liposome systems in terms of effectiveness and efficiency. It is comprised of free fatty acid, cholesterol, and surfactant, which combine to yield better vesicle properties for medication administration. Numerous research endeavors have examined the ideal blend of surfactant types, free fatty acids, and their proportions, along with the formulation elements that might substantially impact the vesicle properties. It has been shown that novasome technology may be used to deliver various drugs, such as vaccines, niflumic acid, zolmitriptan, and terconazole. To develop the most effective novasomal formulations with significant drug loading and nano-metric form, it is important to find the appropriate ratio between core components along with critical manufacturing process determinants. Understanding the interplay between these factors requires applying Quality by Design (QBD) in combination with Design of Experiments (DoE). These may be applied for both scale-up and lab-scale applications. This manuscript includes a detailed view of novasomes and the involvement of QBD.

Objectives: The primary aim of this study was to develop an effective treatment strategy for periodontal diseases that maximizes therapeutic effects while minimizing systemic adverse effects. Specifically, the study focused on creating a xerogel-based localized drug delivery system for the slow release of doxycycline hyclate (DH) to treat periodontal disease.

Methods: Xerogels were prepared using the solvent casting method, with the solvent being evaporated slowly at ambient conditions. The prepared DH xerogels underwent comprehensive characterization to assess their in-silico compatibility, pharmacokinetics, and physicochemical properties. The properties studied included drying time and rate, thickness, moisture content, swelling index, organoleptic properties, scanning electron microscopy, FTIR spectroscopy, differential scanning calorimetry, drug release and kinetics, and antibacterial activity.

Results: In-silico studies demonstrated compatibility between the ingredients, indicating minimal adverse effects on the body. The analysis revealed hydrogen bonding between the drug and polymers, changing the drug's crystallization characteristics to an amorphous form. The release profiles of DH from the xerogels indicated a slow release, ranging from 29.42% to 66.30% over 10 hours, following the Hopfenberg model.

Conclusion: The findings of this study suggest that the formulated xerogels are well-suited for periodontal applications. The slow-release profile of DH from the xerogels offers a promising approach for localized treatment of periodontal disease, reducing the risk of systemic adverse effects. This data is valuable for dental practitioners and pharmaceutical formulators, providing a new avenue for enhancing periodontal disease treatment.

Cancer represents a diverse and complex spectrum of diseases characterized by the abnormal growth and proliferation of cells, establishing a formidable global health challenge. Within the array of diverse cancers, breast cancer arises as one of the primary contributors to cancer-related fatalities in females. Breast cysts, thickenings, alterations in breast size or form, etc., are all prevalent and well-known signs of breast cancer. Despite remarkable progression in cancer research and the abundance of potent drugs, the effectiveness of conventional therapy is still hindered by various complications. In this avenue, nanocarriers present considerable promise for delivering therapeutics to cancerous cells, however, still numerous challenges persist in achieving successful targeted drug delivery and localization. Recent progress has emphasized the utilization of ligand-functionalized nanocarriers to enhance the delivery at target tissues and improve uptake by cancer cells. This approach contributes to increased accuracy and efficacy, which ultimately leads to enhanced patient outcomes. Lactoferrin, a multifunctional glycoprotein, is currently receiving significant attention as a promising ligand for targeted drug delivery in cancerous cells, especially breast cancer cells. This review provides new insight into ligand-targeted therapy, emphasizing the key benefits and notable features of utilizing lactoferrin as a targeting ligand for delivering drug-loaded nanocarriers to tumor sites.