Journal of Drug Targeting最新文献

Mesoporous silica nanoparticles (MSNs) have been studied for the delivery of anticancer drugs because of their unique mesoporous channels. In this study, Biotin was used as a targeting moiety of MSNs for the purpose of breast cancer cell targeting, and then, Gelatine grafting onto the surface of MSNs was carried out using glutaraldehyde-mediated cross-linking as a capping layer. Dynamic light scattering (DLS), Zeta potential change, infra-red spectroscopy (FT-IR), nitrogen adsorption and desorption (BET), and transmission electron microscopy (TEM) was used for the characterisation of size, morphology and other features related to the fabricated nanoparticles (NPs). The gelatine/biotin coated MSNs (MSN@Bio-Gel) were loaded with Doxorubicin (DOX), followed by assessing its drug loading and release behaviour. In vitro experiments were carried out for exploring the antitumor effect of DOX-MSN@Bio-Gel. The size of NPs prepared in this study was in the range of 178-286 nm. The MTT assay showed suitable anticancer activity of the NPs.Confocal microscopy showed that gelatine-coated, biotin-targeted MSNs had higher cell uptake into MCF-7 cancer cells.

Background: Chronic constriction injury (CCI) of the sciatic nerve induces neuropathic pain, inflammation, oxidative stress and neurodegenerative changes, impairing sensory and emotional function. While curcumin is well recognised for its anti-inflammatory and neuroprotective properties, its therapeutic use is limited by poor bioavailability. Curcumin liposomal nanoparticles (CLNs) offer improved delivery and stability.

Methods: Male rats (n = 24) were randomly assigned to control, CCI, CCI + curcumin (60 mg/kg) and CCI + CLNs (40 mg/kg) groups. CCI was induced through sciatic nerve ligation, followed by 14 days of treatment. Behavioural assessments included thermal and mechanical pain sensitivity, anxiety-like behaviour (elevated plus maze), and sciatic nerve function (SFI). Serum inflammatory (tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) and oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) and reduced glutathione (GSH)) were measured, alongside histological analysis.

Results: Compared to curcumin, CLNs showed superior efficacy in improving pain thresholds, anxiety-like behaviours and SFI scores. CLNs significantly lowered TNF-α and IL-6 levels and enhanced SOD activity, with no intergroup differences in MDA, TAC or GSH. Histology confirmed nerve regeneration and reduced neurodegeneration.

Conclusions: CLNs effectively alleviated neuropathic pain, reduced neuroinflammation and improved functional recovery after sciatic nerve injury, while mitigating anxiety-like behaviours.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation, cartilage deterioration, and oxidative stress. The study developed transdermal RA treatment with L-carnosine (CAR)-loaded chondroitin sulphate (CHS) functionalised proposomes. CHS-functionalised proposomes measured 285 ± 0.89 nm, with PDI of 0.31 ± 0.05, zeta potential of -13.6 ± 0.67 mV, and entrapment efficiency of 73.96 ± 0.87. TEM confirmed their spherical shape and homogenous CHS coating. Biphasic drug release in vitro began with 13.2% burst release in 0.5 h and over 8 h, sustained release reached 83.79%. Ex-vivo permeation results revealed that the selected formulation increased CAR flux by 30.97 folds compared to CAR gel. In vivo testing in rats with AIA model showed that group treated with selected formulation demonstrated reduced joint inflammation and soft tissue swelling that was further confirmed by X-ray radiography. ELISA results showed significant reduction in TNF-α and IL-1β and elevation in NRF2 and SOD with levels comparable to the negative control group. Histopathological investigation showed cartilage integrity and proteoglycan content similar to the negative control. The CHS-functionalised CAR-loaded proposomes improved CAR permeation, targeted inflammatory joints, and reduced oxidative stress, making them a viable non-invasive RA treatment.

The aim of the study was to explore the potential of human plasma-derived exosomal gel as a carrier for transdermal drug delivery. Exosomes were isolated from human plasma through a combination of ultracentrifugation and dialysis techniques. Methotrexate (MTX), a weak acid drug with log P 1.53 (low permeability), was utilised as a model drug. MTX was loaded into exosomes using the freeze-thaw method. MTX-loaded exosomes were incorporated into a gel, employing carbopol 940 as a gelling agent. MTX loaded exosomes exhibited a mean size of 162.15 ± 4.21 nm, a polydispersity index (PDI) 0.372 ± 0.024, and a zeta potential of -30.6 ± 0.71 mV. Exosomal gel displayed good physicochemical properties along with desirable rheological behaviour that eased skin application. MTX-loaded exosomal gel exhibited sustained release of 59.14 ± 0.812% of the drug within 72 h at pH 7.4 as compared to nonexosomal gel p < 0.0001. MTX-loaded exosomal gel demonstrated a three-fold increase in skin permeability as compared to MTX loaded gel. Moreover, results of in-vivo studies on the carrageenan-induced inflammation model indicated exosomal gel and MTX loaded exosomal gel reduced inflammation as compared to MTX gel. These findings suggested the potential of exosomes as an emerging platform for transdermal drug delivery, offering enhanced skin penetration.

Gram-negative bacterial sepsis remains a major global health threat, exacerbated by rising antimicrobial resistance and limited efficacy of current therapies. Central to its pathogenesis is lipopolysaccharide (LPS), a potent endotoxin that triggers overwhelming inflammation and organ dysfunction. This review critically evaluates emerging therapies targeting LPS in sepsis. Key strategies include antibiotics disrupting LPS biosynthesis and transport (e.g. zosurabalpin, darobactin), monoclonal and bispecific antibodies, extracorporeal endotoxin removal devices, and novel agents like LpxC inhibitors and nanotechnology-based platforms. Despite promising preclinical and early clinical data, translation to practice is limited by pharmacokinetic challenges, toxicity, resistance mechanisms, and inadequate patient stratification. Anti-LPS antibodies and polymyxins have shown selective benefits but face setbacks in broader trials. Nanotherapeutics and targeted filtration systems like oXiris^® and Alteco^® offer adjunctive potential but require validation through randomised studies. The complexity of LPS biology and sepsis heterogeneity demonstrates the need for precision medicine approaches and biomarker-guided interventions. Addressing scalability, regulatory hurdles, and cost-effectiveness will be critical to integrating LPS-targeted therapies into standard sepsis care. This review outlines a translational roadmap to harness these innovations and improve outcomes in Gram-negative sepsis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesising mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimised nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential -23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An in vivo study of the MC-PLGA-INH-PNPs was performed on a mouse model utilising lipopolysaccharide as an inducer. The data obtained from the in vivo studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.

This study sought to create and characterize a novel antibiotic-loaded keratin-based film bandage for enhanced wound healing. Using the solvent casting method, keratin from chicken feathers was combined with gelatin (KG) in varying ratios to form films. Chitosan microspheres (Mc) were incorporated to achieve sustained release of bacitracin zinc (BZ). The microspheres were evaluated for particle size distribution, encapsulation efficiency, and in vitro drug release kinetics. The optimized film showed a controlled release profile with nearly 76% cumulative drug release over time. Embedding antibiotic-loaded microspheres within the keratin-gelatin matrix enabled prolonged delivery at the wound site, preventing infection and accelerating healing. In vivo excision wound studies demonstrated that the BZ-Mc-KG film achieved complete wound closure by day 20, significantly outperforming the disease control (p < .05). Comparative results indicated that microsphere-loaded gelatin films achieved 90% closure (p < .05), while free drug-loaded keratin-gelatin films reached 98% closure (p < .05). Slower healing was observed with drug-free keratin-gelatin films and standard mupirocin ointment (2.0% w/w). These findings highlight the synergistic potential of chicken feather keratin with BZ, supporting its application as a sustainable biomaterial for advanced wound dressings and effective therapeutic wound care strategies.

This study presents the development of dissolving levonorgestrel-loaded microneedles (LMNs) incorporating a chitosan-β-glycerophosphate thermogelling system for sustained transdermal delivery of levonorgestrel (LNG) as a contraceptive. Polyvinylpyrrolidone K90 and Dextran 40 were included to enhance mechanical strength and controlled drug release. LMNs fabricated using poly dimethyl siloxane moulds exhibited uniform, sharp structures as confirmed by scanning electron microscopy. Fourier transform infra-red and X-ray diffraction analyses demonstrated chemical compatibility and physical stability of LNG within the matrix. The optimised LMNs showed significant mechanical strength (p < 0.05) and high insertion efficiency (F = 17.83, p = 3.03 × 10^-8) across Parafilm^® layers and fully dissolved within 30 min in porcine skin. Ex vivo studies revealed sustained LNG release (70.86% ± 0.42%) over 48 h, outperforming a topical gel (42.33% ± 0.91%). Drug release followed first-order kinetics (R² = 0.996) and non-Fickian diffusion (n = 0.79), indicating a combined diffusion-erosion mechanism. In vivo evaluation in Wistar rats showed significant contraceptive efficacy, with reduced implantation sites (0.5 ± 0.55) and uterine thickness (3.66 ± 0.51 mm; p < 0.0001), comparable to oral LNG. These results highlight LMNs as a promising, minimally invasive platform for long-acting transdermal contraception, offering improved bioavailability, patient compliance and therapeutic effectiveness.

This trial evaluated the effects of insulin aspart (IAsp) and insulin detemir and metformin on islet function in newly diagnosed type 2 diabetes mellitus (T2DM). A total of 96 T2DM patients were randomised into the control group (insulin detemir + metformin treatment) and the study group (insulin detemir + metformin + IAsp treatment), with 48 cases each. The study compared clinical outcomes, as well as changes in fasting plasma glucose (FPG), 2-hour postprandial blood glucose (PBG), glycated haemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-β, quality of life, and sleep quality scores before and after treatment. Compared to the control group, the study group showed a higher total effective treatment rate, lower levels of FPG, 2-hour PBG, HbA1c, FINS, HOMA-IR, and sleep quality scores, while demonstrating higher HOMA-β and quality of life scores (all p < 0.05). Insulin detemir + metformin + IAsp was effective in treating T2DM, significantly enhancing insulin function and blood glucose levels, quality of life, and sleep quality. This combination therapy, though not commonly utilised in newly diagnosed T2DM patients, offers a novel therapeutic approach in clinical practice.

Chitosan, obtained from chitin by deacetylation, is a versatile biopolymer known for its biocompatibility, biodegradability and environmental friendliness. Combined with its chemical and physical modifiability, these properties have made chitosan an important material in biomedical and pharmaceutical fields, especially in drug delivery systems. Chitosan-based nanomaterials exhibit enhanced functions through various chemical modifications such as thiolation, acetylation, carboxylation and phosphorylation, as well as through physical and enzymatic approaches. These modifications address inherent limitations such as poor solubility, limited acid resistance and insufficient mechanical strength, expanding the applications of chitosan in tissue engineering, gene therapy, vaccine delivery, wound healing and bioimaging. This review provides an in-depth analysis of the chemical structure, physicochemical properties and modification strategies of chitosan. It also explores current methodologies for preparing chitosan nanoparticles, along with drug loading and release techniques. Various targeting strategies employed in chitosan-based delivery systems are examined in detail. To illustrate the clinical relevance of these approaches, representative examples from recent therapeutic studies are included. Moreover, it highlights future research directions and the innovation potential of chitosan-based materials.