Aug 2026· Pharmaceutics· Vol 18, pp. 992· 0 citations· 106 references
Medicine
TL;DR
Span 20®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen.
Abstract
Background: This study evaluates transdermal delivery of tamoxifen (TXN) as an alternative to the oral route of administration in treating breast cancer, which is the leading cause of cancer-related death in women globally. Oral TXN, a Class II drug, is associated with first-pass metabolism and serious side effects, including secondary cancers. Objectives: To enhance transdermal delivery, lipid-based transethosomes (TRS) were formulated using three different 24 factorial designs with various non-ionic surfactants, including Tween 20®, Span 20®, and Span 80®. Methods: Optimized TRS formulations were incorporated into HPMC-based gels and characterized for morphology, drug content, pH, viscosity, spreadability, ex vivo skin penetration, and deposition. Additionally, cytotoxicity and stability were assessed. Results: All TXN-TRS gels were suitable for transdermal use; however, Span 20®-based TRS gel demonstrated the highest skin penetration (40.3 ± 1.5 µg/cm2), representing a 127-fold enhancement rate compared with the non-ethosomal TXN gel. In line with the enhanced penetration profile, cellular studies on MCF-7 cells showed concentration-dependent cytotoxicity, reaching 91.24 ± 1.01% inhibition at 2% w/w after 72 h, with an IC50 value of 0.85 ± 0.02% w/w. Stability testing showed all formulations were more stable under refrigeration than at dry room temperature storage, supporting their potential as preclinical transdermal tamoxifen delivery platforms. Conclusions: Span 20®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen.
Histopathological and toxicity studies confirm the antiproliferative effects and safety of the transdermal LLT formulation and support the potential of transdermal LLT formulation to be an effective and safe treatment for BC.
Naifa Alenazi, Z. Khired, Hussam M Shubaily et al.· Journal of liposome research· 0 citations
Objectives: The research aims to develop and optimize transdermal cream containing curcumin, using Shata-Dhauta-Ghrita (SDG) as a traditional lipid base and α-bisbolol as natural permeation enhancer in order to enhance skin absorption and deliver anticancer activities.
Methods: The formulation was assessed for its drug-excipient compatibility to ensure no chemical interactions between curcumin and the selected excipients. To assess transdermal drug transport Ex vivo skin permeation studies were conducted using excised pig skin. In vitro diffusion conducted to evaluate release data. To determine the cytotoxicity and biocompatibility of the formulation MTT cell line assays were also carried out.
Results: In drug excipient compatibility assay, it was found that curcumin assay value in sample was more than 90% and compatible with all excipients. In vitro diffusion showed that optimized batch (F4) has sustained drug release profile and fitted to Hixson–Crowell model (R² = 0.9722), while ex vivo pig skin permeation followed first-order kinetics (R² = 0.9894), indicating concentration-dependent absorption. Further evaluation of the optimized formulation (F4) using SSE and AIC demonstrated that the Hixson–Crowell model best fit for the drug release profile, with the lowest AIC value (−57.04). Skin histopathology demonstrated optimized formulation F4 intact dermal architecture with mild stratum corneum changes, indicating safe permeation. Complementary cell line assays validated the non-toxic nature and effectiveness of the formulation.
Conclusion: Overall, the SDG-based transdermal cream using α-Bisbolol as permeation enhancer exhibited favourable release, permeation, and formulation characteristics, supporting its potential as a promising carrier for curcumin in treating cutaneous cancers.
Poonam Patil, RITESH KARMARKAR· Asian Journal of Pharmaceuti...· 0 citations
Background: Oral administration of sulfasalazine for rheumatoid arthritis is associated with limitations that reduce therapeutic effectiveness. Transdermal delivery using ethosomal vesicles offers a promising strategy to enhance skin penetration and provide localized therapeutic effects. Methodology: Sulfasalazine-loaded ethosomes were formulated using the cold method and optimized using a 3² full factorial design across nine experimental trials. The formulations were characterized for vesicle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and morphology using atomic force microscopy (AFM). The optimized ethosomal formulation was incorporated into a 1% Carbopol 934 gel to prepare the ethosomal gel (EGL). Ex vivo permeation studies were performed using rat skin to compare EGL with a conventional gel (CGL), and flux and permeability coefficients were calculated. Anti-inflammatory activity was assessed in Sprague–Dawley rats. Results and Discussion: Particle sizes ranged from 98.3 ± 2.37 nm to 187.7 ± 3.12 nm, with a negative zeta potential ranging between –24.2 ± 2.56 mV and –32.6 ± 1.35 mV. The entrapment efficiency ranged from 85.33 ± 3.84% to 94.62 ± 1.34%. Vesicles displayed smooth and spherical surfaces. In vitro drug release studies of the ethosomal gel formulations lasted 12 hours, revealing controlled release of sulfasalazine and enhanced ex vivo permeation in the optimized formulation. In vivo studies showed that EGL produced a greater reduction in inflammation compared to CGL. Conclusion: The developed ethosomal gel demonstrated enhanced skin permeation and anti-inflammatory efficacy, making it a promising transdermal delivery system for sulfasalazine in the management of rheumatoid arthritis.
Background/Objectives: Shikonin (SKN) is a potential anti-psoriatic agent, yet its clinical application is hindered by poor water solubility and low stratum corneum permeability. This study aimed to develop a reactive oxygen species (ROS)-responsive hydrogel microneedle system encapsulating SKN-loaded polymeric micelles (SKN-M@MN) to enhance transdermal delivery and evaluate its therapeutic effects in psoriasis. Methods: Shikonin-loaded micelles (SKN-M) were optimised using a thin-film hydration method. SKN-M@MN was fabricated via a two-step casting method using phenylboronic acid-modified hyaluronic acid (HA-PBA) and polyvinylpyrrolidone K90 as the tip matrix. Skin penetration, ROS-responsive release, and anti-psoriatic efficacy were assessed in an imiquimod (IMQ)-induced mouse model. Mechanistic studies included RNA-seq, qPCR, and Western blotting. Results: SKN-M achieved an encapsulation efficiency of 93.45 ± 0.24%, a particle size of 62.49 ± 0.92 nm, and a zeta potential of −36.78 ± 1.12 mV. SKN-M@MN showed 100% skin penetration, sustained drug release, and accelerated degradation under high ROS conditions. In psoriatic mice, SKN-M@MN significantly alleviated skin lesions, reduced epidermal hyperplasia (Ki67), and downregulated IL-17A and TNF-α levels both locally and systemically. Mechanistically, it inhibited the PI3K/AKT and NF-κB signalling pathways. Conclusions: The SKN-M@MN microneedle platform integrates physical skin penetration, ROS-responsive drug release, and pathway inhibition, offering an effective strategy for transdermal delivery of poorly soluble drugs in psoriasis therapy.
Posaconazole is a broad-spectrum antifungal agent with limited oral bioavailability due to poor aqueous solubility
and variable gastrointestinal absorption, necessitating alternative delivery approaches. The present study aimed to
develop and optimize a polymeric matrix-based transdermal drug delivery system to achieve sustained release and
enhanced skin permeation. Transdermal patches were prepared using the solvent casting technique with
hydroxypropyl methylcellulose and ethyl cellulose in varying ratios, along with polyvinylpyrrolidone,
polyethylene glycol 400 as plasticizer, and propylene glycol as permeation enhancer. Preformulation studies
confirmed favourable physicochemical properties, including suitable lipophilicity (log P ~3.18) and compatibility
with excipients. The developed patches were evaluated for physicochemical characteristics, in vitro drug release,
kinetic modelling, ex vivo permeation, surface morphology, and stability. Among all formulations, F7 exhibited
optimal performance with high drug content (99.1%), excellent flexibility, and uniform thickness. It achieved
94.2% drug release over 24 hours with a biphasic profile. Release kinetics followed the Higuchi model with
anomalous transport behaviour. Ex vivo studies demonstrated superior permeation with maximum flux and
minimal lag time. Stability studies indicated minimal variation, confirming robustness of the formulation. The
optimized system shows strong potential for controlled transdermal delivery.
Chinu Kumari, Ajay Kumar, A. Soni· International Journal of Dru...· 0 citations
Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries, necessitating the development of effective localized therapeutic strategies. The present study focuses on the Quality by Design (QbD)-driven development and optimization of an apigenin-loaded chitosan-tethered in situ cubosomal gel for enhanced management of cervical cancer. Apigenin, a potent flavonoid with anticancer and anti-angiogenic properties, suffers from poor aqueous solubility and limited bioavailability, which restricts its clinical application. To overcome these limitations, cubosomal nanocarriers were formulated using glyceryl monooleate and Pluronic® F127, and optimized via central composite design (CCD) by evaluating critical quality attributes, including particle size, polydispersity index (PDI), and % entrapment efficiency. The optimized cubosomes exhibited a particle size of 253.9 nm, a low PDI of 0.06, a zeta potential of -24.4 mV, and an entrapment efficiency of 84.1 ± 1.25%, indicating a stable and efficient delivery system. Transmission electron microscopy confirmed the presence of discrete, cubic nanostructures with uniform morphology. The incorporation of cubosomes into a thermosensitive in-situ gel and surface modification with chitosan significantly improved formulation stability and enabled controlled drug release. The MTT assay revealed superior cytotoxicity of the optimized gel (IC50 = 2.753 ± 0.05 μg/mL) compared to free AGN (IC50 = 6.618 ± 0.15 μg/mL). Confocal microscopy confirmed improved cellular uptake, and the CAM assay demonstrated significant antiangiogenic activity via VEGF/HIF-1α suppression. These findings highlight the potential of CHT-AGN-CB-gel as a promising localized delivery platform for cervical cancer management, offering sustained release and reduced systemic toxicity.
Muskaan Sharma, Devesh Kumar, Mohit Kumar et al.· International Journal of Bio...· 0 citations