Journal of Drug Targeting最新文献

Cardiotoxicity remains the most severe side effect of breast cancer (BC) treatments. Valsartan, an angiotensin II receptor blocker, has antioxidant properties that can mitigate cardiotoxicity-associated BC (CABC). However, valsartan's limited solubility and low bioavailability result in reduced effectiveness. Therefore, this study developed an in-situ nasal pH-responsive valsartan-loaded novasome (ISVLN) to enhance valsartan's sustainability, bioavailability, targeting and efficacy when used alongside chemotherapy to prevent CABC. Various VLN formulations were created and optimised using the Box-Behnken design. The optimal formulation was mixed with chitosan and glyceryl monooleate to develop ISVLN, which was further assessed in vivo using a DMBA-induced breast cancer (DIBC) rat model to evaluate its bioavailability and efficacy. The optimal VLN formulation comprises oleic acid (26 mg), Span 60 (65 mg) and cholesterol (52 mg). The ISVLN formulation improved valsartan's sustainability, permeability and bioavailability compared to free valsartan by 66.40%, 7.46-fold and 4.57-fold, respectively. The ISVLN formulation enhanced valsartan's targeting in both the tumour and heart by 2.30-fold and 1.96-fold, respectively. Compared with the DIBC-positive group, the ISVLN group reduced the tumour volume and mortality rate by 86.20% and 23.53%, respectively. Furthermore, the ISVLN group reduced the LDH and CK-MB levels by 96.11% and 95.97%, respectively. Histopathological analysis confirmed the efficacy of the ISVLN formulation. These findings suggest that a nasal ISVLN could serve as an adjuvant therapy to prevent CABC.

Natural phytoconstituents such as betanin and curcumin have attracted interest for their significant antioxidant and anti-inflammatory properties. Their therapeutic efficacy is notably constrained by inadequate bioavailability and reduced skin permeability. The current study developed an ethosome-based gel system for the delivery of betanin and curcumin, with the objective of improving transdermal penetration and providing sustained anti-inflammatory effects. Ethosomes were formulated by cold method and optimised for physicochemical characteristics including particle size, zeta potential and entrapment efficiency. The optimised formulation exhibited a mean particle size of 202.8 nm, a zeta potential of -56.4 mV and high entrapment efficiencies of 80% for betanin and 85% for curcumin. The characterisation using SEM and FT-IR confirmed the successful encapsulation and structural integrity of the ethosomes. The ethosomal gel demonstrated an optimal pH of 6.5, pseudoplastic viscosity and superior spreadability, making it appropriate for topical use. In vitro diffusion studies demonstrated a sustained release profile lasting 8 h. Skin irritation tests confirmed its biocompatibility. The in vivo anti-inflammatory efficacy was assessed in rats by utilising carrageenan model of inflammation, results showed that ethosomal gel significantly attenuated inflammation in animals. These findings indicate that the ethosome preparation represents a promising approach for enhancing anti-inflammatory efficacy.

A neurodegenerative condition called Alzheimer's disease (AD) is brought on by the buildup of beta-amyloid plaques in the brain. As of right now, AD has no known cure. The only thing the medications on the market can do is slow their development. Nonetheless, nanotechnology has demonstrated its superiority in its application in medicine. It has great promise for AD therapy, mostly in diagnosing the ailment and offering a different treatment method. Penetrating and bypassing the blood-brain barrier (BBB) increases the effectiveness of drug delivery. The most recent advancements in AD diagnosis using nanotechnology based on nanoparticles with optical sensing, electrochemical sensing, and imaging approaches are summarised in this study. When treating AD, nanocarriers help deliver the targeted medication. Since one of the newest and most active treatments for AD is nanomedicines, the main goal of this review is to comprehend the sophisticated application of nanocarriers for targeted drug delivery in AD treatment.

Immune checkpoint blockade targeting the PD-1/PD-L1 (Programmed cell death protein 1/Programmed death-ligand 1) axis has transformed cancer therapy. However, antibodies non-specifically bind to PD-1 or PD-L1 on both malignant and normal cells, resulting in immune-related adverse events and limited therapeutic selectivity. Additionally, antibodies only target cell-surface PD-1/PD-L1, whereas intracellular proteins can translocate to the membrane, enabling immune evasion. In contrast, small interfering RNA (siRNA) can specifically silence PD-1 or PD-L1 on the cell surface and within the cytoplasm, mitigating immune suppression, reducing drug resistance, and limiting systemic off-target effects. Despite the clinical success of immune checkpoint inhibitors, monotherapy benefits only a fraction of patients. Combination therapies incorporating chemotherapy, radiotherapy, or photo-mediated therapy have shown improved efficacy. Nanoparticles offer a promising approach for combination therapy by overcoming RNA delivery challenges, enabling efficient tumour-targeting capacity, providing tumour-responsive behaviour, and versatility for combination therapy. This review presents an overview of different nanoparticles, including polymer and lipid nanoparticles, developed for the codelivery of PD-L1 siRNA and other therapeutic modalities with different properties. Furthermore, discusses mechanisms underlying PD-L1-mediated tumour therapy, and finally, highlights current challenges and perspectives for translating nanoparticle-based combinatorial immunotherapy into clinical applications.

Epigallocatechin gallate (EGCG) exhibits remarkable bioactivities, notably enhancing wound healing via keratinocyte activation and re-epithelialisation. However, its susceptibility to oxidation restricts its efficient application. To address this, this study aims to improve its stability and bioavailability by integrating EGCG liposomes (ELSm) with N-isopropylacrylamide (NIPAM)-modified chitosan (CS) hydrogel (TSCN). Specifically, the TSCN2/5 hydrogel with a mass ratio of CS/NIPAM of 2/5 is injectable and can undergo a reversible phase transition around 30.4 °C, which also exhibits a good adhesive strength of 36.73 kPa. The ELS1 liposomes (the mass ratio of lecithin/cholesterol/EGCG is 40/10/3) demonstrate good stability and encapsulation efficiency, with a particle size of about 110 nm and an encapsulation efficiency of about 85%. Cellular experiments reveal that ELS1 and TSCN2/5 are non-toxic to cells, and the ELSCN hydrogel (composite of ELS1 and TSCN2/5) can increase the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) protein in skin repair. Animal experiments demonstrate that ELSCN with a high concentration of EGCG can promote wound healing by reducing skin inflammation, boosting collagen synthesis, facilitating epidermal repair and promoting granulation tissue formation. Consequently, this composite hydrogel will be used as a coating for efficient skin wound repair.

This study aimed to create nanostructured lipid carriers (NLCs) loaded with pravastatin to improve its long-term anti-hyperlipidemic effects. Preformulation research was conducted. High-shear homogenization and ultrasonication were used to prepare NLCs containing stearic acid (solid lipid), oleic acid (liquid lipid), and varying amounts of Tween 80 and Poloxamer 188 as surfactants. Nine formulations were prepared using a 3² factorial design and evaluated for size, zeta, scanning electron microscopy, entrapment efficiency, release, and kinetics. The optimum formulation was further evaluated for in vivo antihyperlipidemic activity in rats, and the in vitro release profile and stability of the commercial preparation were assessed. The optimized formulation (F4) exhibited an entrapment efficiency of 98.35%, a zeta potential of -65.9 mV, and a particle size of 203.0 nm. Scanning electron microscopy revealed that the particles were spherical and exhibited sustained in vitro drug release (96.4% over 12 hours). In vivo evaluation in hyperlipidemic Wistar rats showed significantly improved lipid profiles and reduced oxidative stress compared to marketed pravastatin tablets. Stability studies confirmed that the formulation was stable under various conditions, and release studies showed sustained release compared with the marketed formulation. These findings suggest that pravastatin-loaded NLCs are promising sustained-release systems for improved management of hyperlipidemia.

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 visualised 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.

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.

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.