Jul 2026· Journal of drug targeting (Print)· pp.
1-18
· 0 citations· 37 references
Medicine
TL;DR
It is suggested that the intratumor SLT formulation provides an effective option for the management of skin carcinoma and has the potential to improve localized therapeutic efficacy and mitigate systemic toxicity.
Abstract
The uncontrolled proliferation of abnormal skin cells is the hallmark of skin carcinoma. Sonidegib (SDB), a potent Hedgehog pathway inhibitor, is clinically approved for the treatment of skin carcinoma. However, its therapeutic utility is restricted by poor bioavailability, high hydrophobicity, and significant systemic adverse effects. This study aimed to develop an intratumor SDB-loaded transbilosomes (SLT) formulation to improve localized therapeutic efficacy and mitigate systemic toxicity. Several SLT formulations were developed and optimized using Design-Expert® software. The optimized SLT formulation was evaluated for safety, intratumor retention, and efficacy using a DMBA-induced skin carcinoma rat model. Results demonstrated that the optimal SLT formulation achieved a 68.87% reduction in drug release after 24 hours compared to free SDB. Pharmacokinetic evaluation revealed a 7.78-fold increase in relative systemic bioavailability compared to oral SDB. In vivo efficacy studies showed an 84.22% reduction in tumor volume in the intratumor SLT-treated group, with no observed fatalities compared to the oral SDB. Histopathological and safety assessments confirmed the significant antiproliferative effects and the favorable preliminary safety profile of the intratumor SLT formulation. These findings suggest that the intratumor SLT formulation provides an effective option for the management of skin carcinoma.
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
Findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localized, and safe platform for advanced breast cancer treatment and validate the superior therapeutic efficacy of the hydrogel.
Maha M. Ghalwash, Randa Mohammed Zaki, Obaid Afzal et al.· Journal of drug targeting (P...· 0 citations
Colorectal cancer treatment remains limited by poor tumor selectivity, systemic toxicity, and insufficient delivery of combination therapies to three-dimensional tumor-like structures. This study investigates the development and application of anti-carcinoembryonic antigen (anti-CEA) conjugated polymeric nanoparticles co-loaded with sunitinib (SUN) and resveratrol (RSV) for the treatment of colorectal cancer. The nanoparticles, formulated using poly(lactic-co-glycolic acid) (PLGA), exhibited favorable physicochemical properties, including a particle size of 207.6 ± 19.0 nm and a negative surface charge of -24.8 ± 0.7 mV. The nanoparticles exhibited controlled and sustained drug release, enabling the prolonged therapeutic efficacy of SUN and RSV. Functionalization with anti-CEA antibodies enabled selective targeting of colorectal cancer cells, as demonstrated by enhanced internalization in HCT-116 cells with high CEA expression. Consistent with this targeting effect, the anti-CEA-conjugated nanoparticles achieved a 29% relative reduction in cell viability against HCT-116 cells compared to non-targeted counterparts in two-dimensional cultures. Furthermore, the SUN and RSV combination exhibited potent synergistic effects across three-dimensional spheroid models. The anti-CEA functionalized system proved more effective, reducing spheroid volume and cell viability by 10% and 14%, respectively, compared to the non-targeted nanoparticles. These findings highlight the potential of CEA-targeted polymeric nanoparticles for co-delivery of synergistic anticancer agents, offering a promising strategy for colorectal cancer therapy.
Punnida Nonsuwan, Kanyanut Insawang, Nattarika Niwetbowornchai et al.· International Journal of Bio...· 0 citations
Skin cancer is one of the most common cancers in the world, and malignant melanoma is the most aggressive and life-threatening form of skin cancer. It often quickly spreads to other parts of the body and may not always respond well to standard treatments. This calls for the urgent development of more effective and targeted treatment strategies. Protein-based nanoparticles have gained considerable attention in oncology owing to their improved bioavailability, tumour-targeted delivery potential, and reduced systemic toxicity. Silk fibroin, a versatile natural biopolymer, has emerged as a promising drug-delivery platform because of its excellent biocompatibility, biodegradability, and structural adaptability. In the present study, spherical silk fibroin-stabilised artemisinin nanoparticles (SF-ARTNPs) were synthesised and evaluated for their anti-melanoma efficacy. The developed nanoparticles demonstrated enhanced stability, improved aqueous dispersibility, high drug-loading efficiency (86.27 ± 2.05%), and a sustained drug-release profile (84.60 ± 7.29%). In vitro cytotoxicity studies revealed that SF-ARTNPs significantly reduced the viability of A375 melanoma cells to 23.31 ± 4.62% at a concentration of 40 µg mL−1, which is further corroborated by scratch assay results indicating suppressed cell migration. Collectively, these findings suggest that SF-ARTNPs have strong potential as an effective nanotherapeutic platform for treating malignant melanoma.
D. Sharda, Amanpreet Kaur, Arnab Pattanayak et al.· RSC Advances· 0 citations
Treatment of melanoma is challenging due to limited bioavailability of chemotherapeutic drugs, side effects, and poor patient compliance with conventional intravenous administration. We evaluated the potential of synthesizing zein microneedles (ZMNs) using curcumin (Cur) as an anticancer model compound as a non-invasive approach for the local treatment of melanoma. A QbD approach was employed to create ZMNs with optimal mechanical strength and membrane penetrability, using zein as the matrix and PVP as a plasticizer at a concentration of 50% (w/v) and 20% (w/v), respectively. ZMNs loaded with Cur at 0.5% drug loading (Cur-ZMNs) demonstrated suitable mechanical properties, desirable membrane insertion, and sustained Cur release in vitro up to 76.17% over 24 h. Ex vivo permeation studies with excised porcine skin showed significantly higher permeation of Cur from Cur-ZMNs (59.75 %) when compared to free Cur (11%). Cur-ZMNs efficiently killed A375 melanoma cells and reduced cell viability by 44%, which was comparable to that of free Cur. The membrane damage of melanoma cells, measured by lactate dehydrogenase (LDH) assay, further supported the cytotoxic effect of Cur-ZMNs against treated cells, while showing no toxic effect against normal fibroblasts, indicating the potential of prepared Cur-ZMNs for effective treatment of melanoma.
C. Jayalakshmi, Mutasem Rawas-Qalaji, Mohamed Haider et al.· Colloids and Surfaces B: Bio...· 0 citations
Pacritinib (PAC), a potent inhibitor of JAK2, is currently being explored as a potential therapeutic agent against GBM, which is an aggressive and vascularized brain tumor, resistant to many therapies. The therapeutic potential of PAC is hindered due to its poor water solubility and low brain bioavailability. In the current study, a PAC-loaded nanoemulsion (PAC-NE) was formulated to deliver the drug through the intranasal (IN) route for better solubilization, nasal absorption, and brain targeting. The optimized formulation of PAC-NE exhibited a mean droplet size of 18.78 ± 0.4 nm and a polydispersity index (PDI) value of 0.183 ± 0.007, representing a highly homogenous and uniform NE, which is appropriate for nasal administration. In vitro evaluation of the anticancer efficacy in 2D cell culture and 3D tumor spheroid model (3DS) proved that PAC-NE greatly improved the cellular uptake, cytotoxicity, and tumor spheroid inhibition activity compared with free PAC. In addition, ex vivo nasal permeation was greatly improved by the optimized formulation, showing a flux value of 1.27 ± 0.06 µg/cm2/h and a permeability coefficient value of 2.4 × 10⁻7 ± 0.19 cm/s, which were significantly higher than that of the plain drug. Moreover, the histopathological examination demonstrated no sign of damage to the nasal mucosa. Pharmacokinetics analysis following IN application revealed that the optimized NE depicted greater brain-targeting ability, where there was an improvement in %DTE by 1.99-fold and in %DTP by 2.75-fold in comparison to free PAC. Overall, from the above observations, it can be concluded that PAC-NE is a non-invasive delivery system which shows promising results for better brain delivery thereby supporting the clinical translation of PAC for GBM therapy.
Anupama Sikder, Shraddha Naresh Katarpawar, Vivek Phatale et al.· European journal of pharmace...· 0 citations
