Journal of Drug Targeting最新文献

This study aims to formulate Clofazimine (CLOF)-loaded nanostructured lipid carriers (NLCs) for transdermal application, thereby improving the overall efficacy of the drug. NLCs loaded with clofazimine were developed using biocompatible lipids, characterised w.r.t. particle size, PDI and % entrapment efficiency and optimised using 'Box-Behnken design'. The optimum formulation was assessed for in vitro drug release, dermatokinetics & in vivo biocompatibility study. The characterisation of NLCs formulation revealed their globular shape with a particle size of around 192 nm, zeta potential of approximately of -30 mV and % EE of around 88.45%. Drug release demonstrated biphasic drug release from NLCs and follows the Higuchi release kinetics with a non-fickian release mechanism. The ex vivo study confirmed a 3.5 folds increase in permeation as compared with conventional gel formulation. Thus, the NLC based formulation exhibited around 350% increase in permeation as compared to plain gel of drug. The developed formulation was found to be biocompatible and exhibited no signs of irritancy or toxicity, according to the skin irritation study. Furthermore, formulation has good physicochemical stability with a shelf life of about 27 months. In conclusion the study suggests that NLC-loaded CLOF was applied topically to treat leprosy, providing improved skin penetration and effectiveness.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel syndrome characterised by inflammation and oxidative deterioration. Our study aimed to investigate provesicular formulations (Pro) as a novel carrier for chrysin (CR) to enhance its efficacy in attenuating chemically induced UC. Chrysin Provesicles (CR-Pro) were prepared using coacervation phase separation technique utilising different edge activators along with Span 40 and cholesterol. Vesicles were characterised by entrapment efficiency percentage (EE%), particle size (PS) and zeta potential (ZP) to select the optimal formulation. In-vitro release experiment was conducted to evaluate the release pattern of drug from the developed formulation. In-vivo efficiency of the developed formulation was assessed utilising inflammatory response and oxidative stress generated by acetic acid administered intrarectally in rats. The vesicles revealed high CR EE% ranging from 94.53 ± 1.97 to 99.66 ± 0.16%, VS ranged from 133.6 ± 2.54 to 331.3 ± 5.25 nm, and high negative ZP values which revealed stable vesicular formulations. In-vivo study results showed that the selected CR-Pro reduced the high colonic NO, TLR4, and NF-κβ levels with increasing GSH and SIRT-1 levels, limiting both oxidative injury and inflammatory response. According to these findings, CR-Pro may be a viable drug delivery approach for encapsulating CR and boosting its effectiveness in UC treatment.

The topical administration of hydrophilic drugs such as minoxidil and minocycline for alopecia and acne treatments remains unsatisfactory due to limited skin absorption and follicular uptake. The combination of physical and chemical enhancement methods may be beneficial in improving skin delivery. In this study, minoxidil and minocycline were topically delivered in nanoparticulate form to penetrate the skin using fractional laser microporation. Skin perforation was conducted on pig skin with a CO₂ laser (2-8 mJ). The lipid-based nanocarriers increased the passive absorption of the drugs as compared to the free form, with a particularly significant increase in flux. The laser enhanced the skin deposition and flux of both free and nanoencapsulated drugs. The follicular accumulation of minoxidil in nanostructured lipid carriers (NLC) and liposomes (LP) was increased by 7- and 9-fold, respectively, with laser treatment. The laser also enhanced follicular minocycline accumulation in NLC and LP by 9- and 12-fold, respectively, compared to passive transport. Biodistribution observed through confocal microscopy illustrated that the nanoparticles were primarily transported through the laser-created microchannels, with both vertical and horizontal diffusion. After CO₂ laser exposure, the nanoparticles were visualized in both epidermal and dermal layers. In an in vivo Cutibacterium acnes-infected mouse model, a 2-log reduction in bacterial colony in the skin was observed with the combined laser and NLC. Our preclinical evidence demonstrates that the combination of laser ablation with specific nanoformulations appears to be an effective and safe strategy for cutaneous and follicular delivery of hydrophilic drugs.

Hyperpigmentation is often driven by ultraviolet (UV)-induced inflammation and melanogenesis. This study aimed to develop a novel, eco-friendly niacinamide (NIA) nano-delivery system to overcome the skin barrier and effectively target both inflammation and pigmentation associated with ultraviolet B (UVB) damage. Employing a Quality-by-Design (QbD) approach, we utilised a D-optimal response surface design to fabricate and optimise solvent-free niacinamide niosomes (NIA-NIs). Particle size (PS) was minimised and zeta potential (ZP) maximised for enhanced stability and skin penetration using novel complete solvent-free ultrasonication method. Morphology was confirmed by transmission electron microscopy (TEM). The therapeutic efficacy of the optimised formulation was validated in a rat-UVB-induced skin-damage model, with outcomes assessed through histopathological examination and inflammatory cytokine quantification. The optimised NIA-NIs exhibited a nano-size of 272 nm ± 9.5 and a high negative charge ZP of -26.9 mV ± 1.2. TEM confirmed spherical morphology and nano-scale size. The niosomal formulation demonstrated profound in vivo superiority in suppressing inflammation, reducing TNF-α and IL-6 levels by 54% and 29%, respectively. Histopathology confirmed near-complete skin architecture restoration, markedly reducing hyperkeratosis, inflammatory infiltration and collagen disruption, effects that were only partial using the free drug. Niosomes significantly enhance NIA's efficacy through targeted delivery, establishing them as a promising and sustainable nano-therapy for effectively treating hyperpigmentation and photo-damaged skin.

Quercetin (QCT) is an effective flavonoid that offers protection against diabetes mellitus-associated heart failure (HF) due to its antioxidant properties. The effectiveness of QCT is, however, constrained by its low bioavailability and poor solubility. An in-situ pH-sensitive formulation of QCT-loaded transbilosomes (IPSQLT) was developed for nasal administration. This formulation aims to enhance sustainability, bioavailability, permeability, and the effectiveness of QCT in treating diabetes-associated HF. To determine the optimal QLT formulation, various formulations were developed using the Box-Behnken design. The IPSQLT formulation was developed by incorporating an optimal QLT formulation along with chitosan and glyceryl monooleate. The in vivo study employed an experimental diabetes and HF-induced rat model to evaluate the bioavailability and effectiveness of the IPSQLT formulation. The IPSQLT formulation enhanced QCT's sustainability, permeability, and bioavailability by 60.64%, 7.11 times, and 7.37 times, respectively, compared to free QCT. The nasal IPSQLT formulation significantly reduced levels of glucose, LDH, CK-MB, troponin-1, and MDA compared to the positive control group, with reductions of 92.52%, 97.89%, 93.22%, 97.60%, and 98.79%, respectively. Additionally, IPSQLT elevated the levels of GSH, SOD, and CAT by 3.41-fold, 3.13-fold, and 3.13-fold, respectively. These findings suggest that nasal IPSQLT could serve as a potential treatment option for diabetes-associated heart failure.

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.

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.

Chronic autoimmune skin disorder known as psoriasis (PSO) is typified by the excessive proliferation of skin cells, which develops thick, red and scaly patches on the skin's surface. These patches may be uncomfortable for people with this illness due to their itching and soreness. Treatments for psoriasis try to lessen inflammation, ease symptoms and slow the proliferation of too many skin cells. Traditional treatment methods for psoriasis, including topical corticosteroids, systemic immunosuppressant and biologics, often struggle with issues like poor patient adherence, systemic toxicity, limited skin penetration and inefficient drug absorption. However, nanotechnology-driven drug delivery systems offer a significant improvement by enhancing pharmacokinetic and pharmacodynamics properties. These systems ensure targeted and sustained drug release while minimising off-target effects, representing a promising new approach to PSO treatment. This article discusses various nano particulate drug carriers that have been developed to enhance transdermal and topical drug delivery. These carriers include liposomes, niosomes, transfersomes, ethosomes, dendrimers, nanoemulsions, solid lipid nanoparticles, nanogels, silver nanoparticles, gold nanoparticles, nanosponges, nanocapsules and nanocrystals. These nanocarriers improve the permeation of drugs across the stratum corneum, facilitate the formation of depots in the epidermis and dermis and enable controlled drug diffusion. This prolongs therapeutic action while reducing systemic exposure.

Acne vulgaris is a common dermatological disorder, with current treatments often limited to poor skin penetration, instability, irritation and suboptimal therapeutic outcomes. There is a pressing need for advanced drug delivery systems that can overcome these limitations and enhance treatment efficacy. This study aimed to develop and optimise a novel tazarotene-loaded emulgel formulation, combining the advantages of emulsions and gels to achieve controlled drug release, improved stability and superior clinical performance in topical acne therapy. The formulation was prepared using the incorporation method and optimised through the Box-Behnken statistical design (BBD). Three independent variables, such as Carbopol 940 (X₁), Span 80 (X₂) and Tween 80 (X₃), were assessed for their effects on drug release (Y₁) and viscosity (Y₂). The optimised formulation exhibited desirable characteristics, including pH: 6.6 ± 0.3, viscosity: 28,945 cPs, spreadability: 6.17 ± 0.02 cm², extrudability: 18 ± 2.49 g/cm² and drug content: 85.46 ± 4.02%. In vitro studies demonstrated 87.59 ± 2.6% drug release over 7 h. A skin irritation test in mice confirmed its dermatological safety, with no signs of erythema or oedema. Anti-acne efficacy, evaluated using a Propionibacterium acnes-induced murine model, revealed complete lesion clearance, outperforming a marketed gel. These findings firmly establish the tazarotene-loaded emulgel as a safe, effective, and superior topical treatment for acne.

Autoimmune diseases represent a heterogeneous group of disorders characterised by immune system dysregulation, wherein aberrant responses to self-antigens result in cellular and tissue damage. According to statistics, there are over 80 different types of autoimmune diseases worldwide, among which psoriasis and rheumatoid arthritis (RA) are relatively common. Current therapeutic strategies emphasise long-term management to mitigate symptoms and retard disease progression. Conventional approaches, including systemic administration of oral medications, injectables, and biologics, are frequently limited by adverse effects that compromise patient adherence. In contrast, the use of microneedle (MN) technology as a minimally invasive transdermal delivery platform has emerged as a promising alternative, offering distinct advantages such as painless self-administration, enhanced patient compliance, localised delivery to disease-specific sites (e.g. skin lesions in psoriasis, inflamed joints in RA), and improved bioavailability of immunomodulatory agents while minimising systemic toxicity. This review systematically examines MN classification, immunomodulatory mechanisms, and therapeutic efficacy in autoimmune disease management, while also providing a critical assessment of MN biosafety and clinical translation challenges in autoimmune patients. Furthermore, it highlights recent advancements in MN technology for prevalent autoimmune disorders, with the goal of informing future innovation and accelerating clinical translation.