Current Drug Delivery - Online First

The toxicity of nontargeted chemotherapy hinders liver cancer treatment. This study developed dual-peptide (SP94/TAT) co-modified liposomes (SP94/TAT-DOX/DTX-LPs) for enhanced targeting and efficacy.

Liposomes encapsulating docetaxel (DTX) and doxorubicin (DOX) were prepared via film dispersion/ammonium sulfate gradient using DSPE-PEG, lecithin, and cholesterol. SP94 (targeting) and TAT (penetrating) peptides were conjugated via organic phase reaction/insertion. Their physicochemical properties, encapsulation efficiency, stability, drug release, and in vitro antitumor activity were evaluated.

Optimized SP94/TAT-DOX/DTX-LPs were spherical (119.6 ± 4.1 nm; PDI 0.161 ± 0.006; zeta -9.84 ± 1.54 mV), and their encapsulation efficiency was high (DOX: 92.97 ± 1.73%; DTX: 80.33 ± 0.96%). Stability was confirmed at 4 °C for 30 days (PDI < 0.2, size change < 10%) and in 50% fetal bovine serum (FBS) for 24 hours (transmittance > 90%). Sustained release showed 68.2 ± 3.5% (DTX) and 74.8 ± 2.9% (DOX) cumulative release at 48h (PBS pH 7.4). In vitro, SP94/TAT-DOX-LPs showed 2.3-fold higher HepG2 cellular uptake versus single-modified liposomes (p<0.001), with minimal LO2 uptake. Cytotoxicity assays revealed a 3.11-fold lower IC50 (0.096 ± 0.026 μg/mL) versus unmodified liposomes (0.299 ± 0.103 μg/mL). Apoptosis was significantly higher (39.5% in HepG2) than in single-modified formulations (20.55–26.74%).

SP94/TAT-LPs enable dual-stage targeting: SP94 targets liver cancer cells, and TAT enhances penetration, significantly improving in vitro antitumor activity. Study limitations include sole in vitro validation (HepG2/LO2), small sample size (n=3), parameter variability, and lack of in vivo data on targeting, pharmacokinetics, and toxicity.

SP94/TAT-DOX/DTX-LPs achieved effective dual-stage targeting and synergistic cytotoxicity. High encapsulation, stability, and sustained release support their potential as a targeted platform for liver cancer therapy, reducing off-target toxicity.

Frankincense Essential Oil (FREO) has demonstrated curative potential in Ulcerative Colitis (UC) patients. However, the inherent instability of FREO results in its relatively low bioavailability. Therefore, the present study aimed to develop a novel oral O/W type FREO Submicron Emulsion Formulation (FREO-SE). This was achieved by encapsulating FREO within submicron emulsion droplets, with the further objective of elucidating the anti-UC efficacy of FREO-SE.

A single-factor experimental approach was employed to screen the formulation, dosage, and preparation process of FREO-SE. Subsequently, the Box-Behnken Design (BBD) was utilized to optimize the submicron emulsion preparation procedure. The quality of the prepared emulsion was evaluated. Finally, a comparative analysis of the anti-ulcerative colitis efficacies of FREO and FREO-SE was conducted using a UC mouse model. The mechanism of action of FREO-SE was further examined through immunohistochemistry, with the ultimate goal of enhancing the stability of FREO and elucidating its therapeutic effects on ulcerative colitis.

The optimal formulation and manufacturing process for FREO-SE were established, and the particle size, PDI, and Zeta potential were characterized, with values of 105.09 ± 1.27 nm, 0.30 ± 0.02, and -37.43 ± 0.97 mV, respectively, confirming the successful preparation of FREO-SE. In DSS-induced UC mice, FREO-SE significantly reduced the DAI score compared with the DSS group. The weight loss of the FREO-SE-H group mice was significantly reduced (p < 0.001), and the shortening of colon length was significantly reduced (p < 0.001). Serum TNF-α and IL-6 levels were significantly reduced (p < 0.001), thereby alleviating colonic tissue lesions. The expression of p-ERK and p-P65 in colon tissue was significantly reduced (p < 0.001). In conclusion, FREO-SE inhibited the levels of p-ERK and p-P65 in MAPK and NF-κB signaling, and demonstrated a definite therapeutic effect in a mouse model of ulcerative colitis.

This study confirmed that the FREO-SE formulation notably potentiates the therapeutic efficacy of FREO against UC, with its mechanism underlying modulation of the MAPK/NF-κB inflammatory signaling pathway.

The preparation process of FREO-SE is characterized by stability, simplicity, and controllability, endowing it with excellent stability. FREO-SE exhibits a protective effect against DSS-induced UC in mice and demonstrates significant efficacy in the ulcerative colitis mouse model.

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.

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. BF-QUE NS was characterized by observing morphology, measuring particle size and zeta potential, X-ray 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.

The optimal synergistic ratio of BF to QUE was 3:2. The mass ratio of BF and QUE in BF-QUE 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 tumor-bearing mice, along with high safety profiles.

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

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. BF-QUE NS shows potential for clinical application as an anti-liver tumor drug.

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).

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.

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.

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.

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

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 Tigecycline-loaded 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.

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.

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.

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.

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.

One of the least invasive, recognized potential routes for both local and systemic drug delivery and the most patient-friendly methods of administering therapeutic agents is transdermal drug delivery. It minimizes gastrointestinal side effects, prevents hepatic first-pass metabolism, lowers dosage frequency, and boosts patient compliance.

This review aims to examine the nanostructured systems for transdermal drug delivery, focusing on their types, design, development and mechanism in enhancing drug permeation through the skin.

This review article synthesized findings from recent studies on nanostructured systems used in transdermal drug delivery systems. With a particular focus on offering a comprehensive understanding of transdermal drug delivery methods and augmentation strategies, the author examines current trends and potential uses of transdermal technologies.

Nanostructured systems have shown increased drug penetration, improved bioavailability and controlled release profiles.

Nanostructured systems offer a versatile and effective approach to overcoming the limitations of traditional transdermal drug delivery methods. Future research should focus on optimizing these systems for clinical applications, ensuring safety and regulatory compliance.