Current drug delivery最新文献

The integration of nanotechnology with biomaterials has opened new avenues in drug delivery and tissue engineering, enhancing therapeutic efficacy and patient outcomes. Nano-sized biomaterials (1-100 nm) demonstrate unique properties that improve drug targeting, reduce side effects, and facilitate tissue regeneration. This review highlights the multifunctional applications of nanoparticles, particularly selenium nanoparticles, in cancer therapy and regenerative medicine. By optimizing interactions with biological systems, these advanced materials are poised to revolutionize treatment protocols, offering targeted therapies that combine diagnostics and therapeutics. The potential of nanobiotechnology in clinical applications underscores its critical role in advancing personalized medicine.

The eye is one of the primary structures of the body that allows perception of the entire world. A person's activities rely entirely on having good vision, and any diseases or problems encountered with vision create a troublesome condition in life. Ocular delivery can potentially treat numerous eye-related disease conditions. The diseases that affect the eyes include glaucoma, dry eye syndrome, cataracts, conjunctivitis, diabetic retinopathy, keratitis, uveitis, Endophthalmitis, allergies, and others. The conventional dosage forms (eye drops, ointment) pose numerous challenges in treating ocular infections owing to their complex nature and several barriers. Recent advances in artificial intelligence and machine learning provide a preliminary diagnosis in the early stages of disease identification and are also useful during retinal surgery. The poor ocular penetration, low bioavailability, short retention time, and frequent administration are the limitations of conventional treatments. These limitations are easily solved with nanotechnology-driven approaches. The current state-of-the-art review explores eye physiology, barriers (precorneal, corneal epithelium, lacrimal sac, blood-ocular, and efflux protein), limitations of the conventional and nanotechnology-based delivery (Lipid-based, polymer-based, metal and inorganic NPs, vesicle-based NPs, and miscellaneous). These nanocarriers facilitate good permeation, extended retention time, augment solubility, improve bioavailability, improve patient comfort and compliance, and minimize dosage application. The nanocarriers are equally effective in treating the anterior and posterior regions of the eyes, whereas conventional ones have failed to treat them effectively. The recently approved agents and patents are elaborated on ocular drug delivery. Advancements in stem cell and gene therapy are also gaining attention for treating inherited and acquired retinal diseases.

Breast cancer (BC) continues to be the most prevalent cause of death from cancer on a global scale, requiring novel and targeted therapeutic strategies. Peptide-loaded nanoparticles (NPs) have been established as a prospective platform for precision drug delivery in BC treatment, providing enhanced cancer selectivity, improved drug stability, and reduced systemic toxicity. This article explores the multifaceted utilizations of peptide-loaded NPs in BC therapeutics, highlighting advancements in targeted drug delivery, combination therapy, and vaccine development. Peptideloaded NPs have demonstrated superior efficacy in delivering chemotherapeutic agents, overcoming drug resistance, and minimizing adverse effects. Studies on tumor-homing peptides, such as F3- functionalized liquid crystalline NPs and tLyP-1-modified reconstituted high-density lipoprotein NPs, have shown significant improvements in drug accumulation at tumor sites, reduction in metastasis, and prolonged circulation time. Additionally, the creation of peptide-based vaccines targeting tumor-associated antigens, including HER2/neu and heat shock protein 90 (HSP90), is reshaping BC immunotherapy, stimulating strong immune responses against tumors. Despite these advancements, obstacles persist in ensuring NP stability, mitigating immunogenicity, and scaling up manufacturing for clinical translation. Future directions include the integration of peptide-loaded NPs with CRISPR/Cas9 for gene-editing applications, the development of peptide nanovaccines, and the use of personalized nanomedicine approaches tailored to the molecular profiles of individual tumors. This review underscores the potential of peptide-loaded NPs as a next-generation therapeutic strategy, facilitating the development of more efficient and personalized treatments for BC.

Introduction: Both bufalin (BF) and quercetin (QUE) have demonstrated significant antitumor potential. However, they suffer from poor solubility and low bioavailability, which largely limit their clinical application. In order to increase the antitumor activity of BF and QUE by synergistic effect, BF and QUE co-loaded nanosuspension (BF-QUE NS) was developed.

Methods: The MTT method was used to determine the viability of HepG2 cells after treatment with BF and QUE at different mass ratios, and the optimal combination ratio was screened. BF-QUE NS was prepared by the anti-solvent precipitation method, and the single factors affecting its preparation were investigated to optimize the formulation and preparation process of the best combined NS. BFQUE NS was characterized by observing morphology, measuring particle size and zeta potential, Xray diffraction, differential scanning calorimetry, and drug release in vitro. Cytotoxicity was detected using the MTT method; the uptake of BF-QUE NS by HepG2 cells was observed by laser confocal microscopy and flow cytometry; apoptosis of HepG2 cells was detected by flow cytometry. BF-QUE NS was systematically characterized, and H22 tumor-bearing mice were further used to investigate the targeting distribution, antitumor effect.

Results: The optimal synergistic ratio of BF to QUE was 3:2. The mass ratio of BF and QUE in BFQUE NS was 1.47:1. The optimized BF-QUE NS exhibited an average particle size of 238.4 ± 2.1 nm, polydispersity index of 0.250 ± 0.004, zeta potential of -22.2 ± 0.3 mV, and presented good short-term physical stability. In vitro and in vivo experiments demonstrated that BF-QUE NS exhibited significant liver tumor-targeting efficacy, achieving an inhibition rate of 72.59% in H22 tumorbearing mice, along with high safety profiles.

Discussion: BF-QUE NS provides a practical solution to the delivery challenges of poorly soluble anti-cancer drugs.

Conclusion: The prepared BF-QUE NS enhanced the drug solubility and promoted the targeted accumulation in tumors, thereby strengthening the synergistic anti-tumor effect of BF and QUE. BFQUE NS shows potential for clinical application as an anti-liver tumor drug.

The medicine is constantly released via a sustained and regulated drug delivery system per unit. However, there are several situations where it is undesirable to keep a drug's blood level constant. In these circumstances, pulsatile drug delivery could be preferable. Pulsatile drug delivery systems (PDDS) are gaining popularity because they deliver the medicine to the correct site of action at the proper time and in the right amount, offering spatial and temporal delivery and boosting patient compliance. These are essentially time-controlled drug delivery systems in which the system manages the lag time independent of environmental parameters such as pH, enzymes, gastrointestinal motility, etc. PDDS can be divided into three categories: time-controlled systems, where the delivery system controls drug release primarily; stimuli-induced systems, where release is programmed by external stimuli like magnetism, ultrasound, electrical effect, and irradiation; and externally regulated systems, where external stimuli like the pH or enzymes present in the intestinal tract or enzymes present in the drug delivery system control release. This article discusses several systems, such as capsular, osmotic, single- and multiple-unit systems based on soluble or erodible polymer covering and rupturable membranes. It summarizes the most recent technical innovations, formulation parameters, and system release profiles. This study also includes products available as once-daily formulations based on pulsatile releases, such as Pulsincap®, OROS®, CODAS®, and Pulsys®. These systems are helpful for medications with chronopharmacological behavior that need night-time dosage, pharmaceuticals with a first-pass solid action, and a particular location of absorption in the GIT. Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular ailments, arthritis, attention deficit syndrome in children, and hypercholesterolemia. PDDS can potentially bring new developments in the therapy of many diseases.

In recent years, tremendous progress in the field of novel drug delivery systems (NDDS), which has prompted the creation of new strategies to enhance treatment results and patient compliance. The goal of this comprehensive review is to provide a summary of the NDDS that the US Food and Drug Administration (USFDA) has approved from 2019 to 2023. Various databases, including PubMed, Scopus, USFDA, and patent websites were utilized to gather relevant information. The selected NDDSs were categorized based on their delivery route, such as oral, injectable, transdermal, pulmonary, nasal, ocular, and implantable. For each delivery route, the review provides a detailed analysis of the approved NDDSs, including their mechanisms of action, advantages, limitations, and clinical applications. Additionally, the review discusses the challenges faced during the development and commercialization of these systems, as well as the prospects and potential areas of improvement. The findings of this comprehensive review demonstrate the remarkable progress made in the field of NDDSs, with the USFDA approving several innovative technologies in recent years. The approved NDDSs have shown promising results in enhancing drug stability, bioavailability, and controlled release, leading to improved therapeutic outcomes and patient convenience. In conclusion, this comprehensive review provides a valuable resource for researchers, healthcare professionals, and pharmaceutical industries, offering insights into the latest advancements in NDDSs approved by the US FDA. The knowledge gained from this review can guide future research endeavors, foster innovation, and contribute to developing more effective and patient-friendly NDDS strategies.

Background: Head and neck squamous cell carcinomas (HNSCCs) require precise treatments. Cetuximab (Ceb) targets EGFR, and copper (Cu) compounds show promise in cancer therapy. This study investigates Ceb-Cu-p-NC, a nanoengineered drug delivery system, designed for enhanced HNSCC treatment. The objective of this study is to evaluate the potential of Ceb-Cu-p-NC in HNSCC treatment.

Methods: Cu precursor, Ceb, poloxamer-407, and hyaluronic acid were used to synthesize Ceb-Cu-p- NC. Fluorescence microscopy and UV spectrophotometry were utilized to determine Ceb integration efficiency, cellular interactions, and drug concentration. Drug release was assessed via in-vitro studies at pH 5.4 and 7.4. Studies using A-253 cell lines were conducted to analyze cytotoxicity, viability, apoptosis, and cell cycle arrest.

Results: In this study, Ceb-Cu-p-NC showed size reduction (85-120 nm) and zeta potential shift. The Ceb integration was 34.92% with 82.5% entrapment efficiency. Cytotoxicity studies revealed enhanced efficacy (IC50: 27.55 mg/mL - 51.47 mg/mL). Flow cytometry showed significant apoptosis and S-phase cell cycle arrest, with statistically significant results (p < 0.05).

Discussion: Ceb conjugation to Cu-p-NC enhanced nanoparticle stability, reduced surface charge, and enabled targeted, controlled drug release. The formulation showed superior cytotoxicity, apoptosis induction, and S-phase arrest in A-253 cells compared to free Ceb, highlighting its potential as an effective targeted therapy for head and neck cancer.

Conclusion: Ceb-Cu-p-NC demonstrates targeted efficacy against HNSCCs, with controlled release, increased cytotoxicity, and apoptosis.

Introduction: Burn wounds are painful injuries that demand immediate and effective management. Conventional wound care solutions often have limitations, such as discomfort during application or removal and potential damage to healing tissue. Therefore, developing novel wound dressings that support biological processes and promote wound healing is highly beneficial. Electrospun nanofibers have emerged as a promising platform for the development of biomedical wound dressings due to their unique structural and functional properties. This study evaluates the burn wound healing potential of electrospun nanofibers composed of aloe polysaccharides, sodium alginate, and Polyvinyl Alcohol (PVA), impregnated with Silver Nanoparticles (AgNPs).

Method: AgNPs were synthesized using a green approach, employing Aloe vera as a reducing agent. Characterization of AgNPs was performed using UV-vis spectroscopy, FTIR, zeta potential analysis, and TEM. Aloe polysaccharides were extracted using ultrasonication and characterized via FTIR, XRD, and DSC. The extracted polysaccharides were then blended with PVA and sodium alginate to fabricate electrospun nanofiber sheets, into which the synthesized AgNPs were incorporated and analyzed for antibacterial, angiogenesis, and in vivo studies.

Results: AgNPs exhibited spherical morphology with sizes ranging from 20 to 27 nm under TEM. Electrospun nanofiber sheet displayed a uniform structure with an average fiber diameter of 129 nm, as confirmed by SEM analysis. A sustained release of silver ions (78.98 ± 0.61% over 48 hours) was observed. The nanofibers exhibited strong antibacterial activity against Escherichia coli and Staphylococcus aureus, promoted angiogenesis, and significantly enhanced wound healing in a burn wound model.

Discussion: AgNPs impregnated nanofiber sheet exhibited superior wound healing, angiogenesis, and antibacterial properties ideal for wound healing applications. The nanofiber sheets mimicked the extracellular matrix and supported angiogenesis. Enhanced wound closure in vivo studies confirmed the therapeutic potential of the nanofibers.

Conclusion: AgNPs-impregnated nanofiber sheets offer antibacterial activity and support angiogenesis, suggesting their potential as a multifunctional wound dressing for effective burn treatment.

Background: In the current era, the importance of pharmaceutical technology and research in innovating novel drugs and formulations is undeniable.

Objective: This study aimed to produce a nanoscale drug delivery system for the simultaneous delivery of repurposed disulfiram (DSF) and celecoxib (CXB).

Methods: The co-formulation was prepared utilizing the emulsification ultrasonication technique to enhance the anti-cancer activity through NLCs. The surface morphology of the optimized NLCs was examined using TEM, while physicochemical characterization analyses employed FTIR, DSC, PXRD, and TGA. In-vitro cell uptake studies were conducted through MTT assay, confocal microscopy, and flow cytometry, respectively.

Results: The optimized DSF-CXB NLCs demonstrated a mean particle size of 144.2 nm, with a drug loading of 9.8% for DSF and 9.87% for CXB. The re-dispersibility index was measured at 103.26%, indicating effective dispersion. Stability analysis over 30 days confirmed the formulation's high stability. Transmission electron microscopy revealed spherical-shaped nanoparticles. Fourier transform infrared spectroscopy indicated no interaction between excipients and the formulation. Both DSC and PXRD techniques affirmed complete encapsulation of both drugs in the NLCs. In-vitro cytotoxicity of DSF-CXB NLCs exhibited a concentration-dependent increase compared to free DSF and CXB solutions in breast cancer cells. Confocal microscopy and flow cytometry studies demonstrated time-dependent internalization of the optimized formulation in 4T1 cancer cells.

Conclusion: These results suggest that repurposing DSF and CXB NLCs holds promise as a co-delivery system for various cancers, potentially leading to improved therapeutic outcomes.

Introduction/objective: Methicillin-Resistant Staphylococcus Aureus (MRSA) is a major cause of purulent Skin and Soft-Tissue Infections (SSTIs), posing significant global health and economic challenges. This study aims to optimize a drug delivery system, specifically Tigecyclineloaded transfersomes, to address the limitations of current treatments, including bacterial resistance, systemic side effects, and poor drug penetration, thereby offering a safer and more effective alternative for MRSA-related SSTIs.

Methods: A novel Tigecycline transfersomal formulation was developed using the thin film hydration method. The study investigated the effects of varying drug-to-lipid ratios, lipid-to-edge activator ratios, and different hydration media on the characteristics of the Tigecycline-loaded transfersomes. The formulation's morphology, release profile, and antibacterial activity against clinical MRSA strains were also evaluated.

Results: The Tigecycline-loaded transfersomes were successfully prepared with particle sizes ranging from 92.3 to 290.8 nm, zeta potential values from -16.22 to -48.7 mV, and encapsulation efficiencies ranging from 54.8% to 84.39%. The formulation prepared using distilled water as the hydration medium, a lipid-to-edge activator ratio of 80:20, and a drug-to-lipid ratio of 3:8 was selected for further assessment due to its optimal characteristics. The selected transfersomes were spherical with an average diameter of 131 nm. The formulation exhibited a controlled drug release profile and demonstrated a twofold increase in antibacterial activity against MRSA compared to non-liposomal Tigecycline.

Discussion: The results highlighted the significant role of formulation parameters in tailoring transferosomal characteristics and enhancing therapeutic performance. The study builds on existing research by introducing Tigecycline-a broad-spectrum antibiotic-into transfersomal systems for the first time. However, further in vivo validation is necessary.

Conclusion: Tigecycline-loaded transfersomes demonstrated improved drug delivery and antibacterial efficacy against MRSA. This novel formulation shows promise as an effective topical therapy for antibiotic-resistant SSTIs.