Search Results (2,297)

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations. Full article

Background/Objectives: This paper describes the synthesis of silica nanoparticles (SiNPs) and their surface modification with amino and phosphate groups (SiNPs-NH₂-PO₃). The functionalized nanoparticles were subsequently loaded with the anticancer drug 5-fluorouracil (SiNPs-NH₂-PO₃-5-FLU) and further modified with PEG2000 (SiNPs-NH₂-PO₃-5-FLU-PEG2000). Methods: In this study, a one-step, two-phase, sol–gel method carried out at room temperature was used to synthesize the nanoparticles. The size and surface zeta potential of the created SiNPs were determined by DLS measurements. HPLC was used to determine the amount of drug loaded into silica nanoparticles and the drug release profile in two different pH environments (slightly acidic and physiological). Based on physicochemical characteristics, the SiNPs-NH₂-PO₃-5-FLU and SiNPs-NH₂-PO₃-5-FLU-PEG2000 formulations were chosen for comprehensive characterization. The cytotoxicity of the studied complexes was assessed in MCF7 breast cancer cells, while their ability to induce apoptosis in those cells was examined using specific immunofluorescence markers: active caspase-7, active poly(ADP-ribose) polymerase (PARP), and p53 protein. Results: Our findings demonstrate that SiNPs-NH₂-PO₃-5-FLU can induce a stronger apoptotic response than free 5-FLU at equivalent concentrations. We observed that drug release occurs not only under physiological conditions but is further enhanced in a mildly acidic environment (pH 5.0), characteristic of the tumor microenvironment. Conclusions: Most 5-fluorouracil formulations are administered as injectable solutions, resulting in systemic exposure and significant adverse effects. However, their encapsulation within nanoparticles could favor preferential drug release in the acidic tumor microenvironment, thus supporting targeted therapy and reducing toxicity to healthy tissues. Moreover, PEGylation of the nanoformulation allows prolonged and controlled release. Full article

Hyaluronic acid (HA) hydrogels have attracted increasing interest for biomedical applications due to their tunable properties and biocompatibility. Methods: In this study, hyaluronic acid HA-based hydrogels were developed using two distinct crosslinking strategies: physical crosslinking through poly(vinyl alcohol) (PVA) incorporation and covalent crosslinking via DCC/NHS-mediated reactions. Piroxicam (Px) was included as a model drug to evaluate the drug delivery potential of the resulting systems. The hydrogels were characterized in terms of morphology, swelling behaviour, adhesion, enzymatic degradation, drug release, and in vitro cytocompatibility. Results: The results indicate that formulation parameters significantly influence the overall performance of the systems. PVA-containing hydrogels exhibited higher swelling capacity and improved adhesive properties, while covalently crosslinked networks showed reduced swelling and enhanced structural stability and resistance to enzymatic degradation. Drug release profiles were dependent on network structure, with more compact systems displaying slower release behaviour. In vitro assays suggested that the developed hydrogels are cytocompatible and that drug incorporation influences both release kinetics and cellular response. However, it should be noted that the biological evaluation was performed under simplified in vitro conditions, which primarily reflect specific aspects such as cell viability and migration. Conclusions: This study provides a comparative analysis of physical and covalent crosslinking strategies within a HA platform and highlights how formulation variables influence key physicochemical and biological properties. These findings contribute to the rational design of HA-based hydrogels, although further studies are required to establish their performance in more complex biological environments. Full article

Background/Objective: The introduction of Ketoconazole (KZ, Nizoral^®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol^® 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the C_max of the lead KZ-NEC formulation (14.4 ± 1.1 μg/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 ± 0.5 μg/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections. Full article

The low water solubility of numerous drug candidates and phytochemicals continues to pose a significant challenge in pharmaceutical development, greatly limiting their bioavailability and therapeutic performance. This review presents a detailed overview of formulation strategies aimed at improving the solubility and dissolution of poorly aqueous-soluble compounds. The biopharmaceutics classification system and the relevance of in vitro–in vivo correlation, as well as key challenges in formulation development, are briefed. Solid-state and particle engineering approaches, including micronization, supercritical fluid technology, electrospinning, and cryogenic techniques, are discussed. Extensive critical examination of amorphous solid dispersions and their preparation methods, as well as crystallization inhibition strategies, is covered. Cocrystallization is highlighted as a promising approach, with emphasis on design principles and preparation methods. Various solubilization techniques, such as pH modification, cosolvency, hydrotropy, micellar solubilization, and cyclodextrin-based complexation, including advanced hybrid systems, are also explored. Emerging solvent platforms, such as deep eutectic systems and lipid-based and nanotechnology-driven approaches, are reviewed for their role in improving solubility and drug delivery. Additionally, enabling technologies such as liquisolid systems and hydrophilic polymers are addressed. Despite notable progress, limitations such as scalability, reproducibility, regulatory constraints, and long-term safety persist. Overall, this review provides integrated insights into formulation design approaches to enhance the solubility and therapeutic efficacy of poorly soluble drugs. Full article

Glioma, the most common and aggressive primary brain tumor, presents significant clinical management challenges due to difficulties in blood–brain barrier penetration, high tumor heterogeneity, and susceptibility to drug resistance and recurrence, leading to an extremely poor prognosis. Traditional Chinese Medicine (TCM), particularly its derived active ingredients and herbal formulations, with its advantages of multi-component, multi-target, and holistic regulation, demonstrates significant potential in the comprehensive treatment of this disease. This review systematically outlines the research progress in TCM for combating glioma. Regarding mechanisms of action, active TCM components not only directly inhibit tumors by inducing cell apoptosis but also exert synergistic therapeutic effects via multiple pathways. These include remodeling the immunosuppressive microenvironment, activating novel cell death programs such as ferroptosis and immunogenic cell death, intervening in tumor metabolic reprogramming, and reversing chemotherapy resistance. In terms of overcoming delivery barriers, drug delivery systems represented by nanocarriers, liposomes, and extracellular vesicles, combined with the penetration-enhancing effects of aromatic orifice-opening herbs (a class of TCM medicinals traditionally used to “open the orifices” and awaken the mind, now recognized to transiently enhance BBB permeability), have significantly improved the brain-targeting efficiency and bioavailability of TCM components. For clinical translation, a number of innovative drugs derived from TCM, such as elemene, cinobufagin, and ACT001, are currently under clinical investigation, with initial results showing efficacy in prolonging survival and improving quality of life. In the future, by integrating the analysis of multi-target synergistic mechanisms, promoting the clinical translation of intelligent drug delivery systems, and conducting high-quality clinical research on integrated Chinese and Western medicine, TCM is expected to provide a new generation of integrated treatment strategies for glioma that combines holistic and precision medicine. Full article

Boswellic acids (BAs), the major bioactive constituents of Boswellia serrata oleo–gum resin, exhibit well-documented anti-inflammatory and antioxidant activities, which correspond to their healing effects in arthritis, inflammatory bowel disease, asthma, metabolic syndrome, liver disorders, and certain cancers. However, their therapeutic potential is hindered by their poor aqueous solubility, low intestinal absorption, extensive metabolism, and overall low oral bioavailability. This review provides a comprehensive analysis of conventional Boswellia serrata products and advanced drug delivery systems designed to enhance the biological performance of BAs. We summarize recent developments in formulation strategies, including phytosomes, micelles, self-emulsifying drug delivery systems, solid lipid particles, polymeric nanoparticles, hydrogels, cyclodextrin complexes, metal-based nanocarriers, and hybrid delivery platforms. Available in vivo and cellular studies are critically evaluated, with a focus on disease-specific outcomes. Results indicate that emerging formulation technologies significantly increase the oral absorption, systemic exposure, and biological effectiveness of BAs. However, despite promising preclinical data, challenges remain regarding the standardization of Boswellia extracts, the stability of novel formulations, their safety, and limited clinical evaluation. By comparing the advantages and limitations of conventional preparations with modern drug delivery systems, this review outlines the most effective strategies to enhance the bioavailability of BAs and highlights future research directions for their translational development. Full article

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit. Full article

Fungal infections remain a major and growing global health concern, particularly in immunocompromised populations and in settings where antifungal resistance is increasing. Imidazole antifungals continue to play an important role in the treatment of superficial and mucocutaneous mycoses because they inhibit lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis. This mechanism disrupts fungal membrane integrity and underlies their clinical utility. However, the effectiveness of imidazoles is increasingly limited by resistance mechanisms such as CYP51 mutations, efflux pump overexpression, and biofilm-associated tolerance. In parallel, several biopharmaceutical constraints, including poor aqueous solubility, limited tissue penetration, short residence time, and variable local drug exposure, further reduce therapeutic performance. This review critically examines the medicinal chemistry, mechanism of action, and resistance biology of imidazole antifungals, while also highlighting the role of pharmacokinetic and pharmacodynamic limitations in treatment failure. Particular attention is given to emerging drug delivery approaches, including lipid-based systems, vesicular carriers, nanocarriers, and other advanced topical formulations, which are being developed to improve solubility, enhance tissue retention, and sustain antifungal exposure at the site of infection. By integrating resistance mechanisms with formulation science, the review provides a translational perspective on how imidazole antifungals may be optimized for improved clinical utility and resistance management. Full article

This study aims to develop and systematically evaluate a new lipid-based formulation of blueberry anthocyanins, which can accelerate the healing effect of the cornea. The study first successfully screened and optimized the formulation and preparation process for blueberry anthocyanin liposomes. Characterization via transmission electron microscopy and dynamic light scattering revealed uniformly distributed, near-spherical liposomes with distinct phospholipid bilayers. Key physicochemical parameters—particle size, zeta potential, encapsulation efficiency, and drug loading capacity—all met formulation standards. In vivo pharmacodynamic experiments demonstrated that topical administration of blueberry anthocyanin liposomes significantly accelerated the repair process and effectively mitigated depressional damage to the corneal epithelium in a New Zealand white rabbit corneal injury model induced by 10.6 μm mid-infrared CO₂ laser. In summary, the blueberry anthocyanin liposomes successfully prepared in this study exhibit excellent performance, effectively enhancing drug exposure levels in vivo and promoting corneal repair. This provides reliable experimental evidence for the development of plant natural active ingredients in ophthalmic treatments. Full article

Background/Objectives: Breast cancer remains a leading cause of cancer-related mortality worldwide, primarily due to the systemic toxicity and drug resistance associated with conventional doxorubicin (DOX) therapy. To overcome these limitations, we developed and optimized a novel cationic-ionizable lipid nanoparticle platform, QTPlus, for the co-delivery of DOX and siRNA targeting fibroblast growth factor 2 (siFGF2). Methods: The study evaluated the physicochemical properties, cellular uptake, gene regulation, apoptosis induction, and in vivo antitumor efficacy and safety of QTPlus-DOX-siFGF2 in breast cancer models. Results: QTPlus nanoparticles based on the A-066 formulation achieved uniform particle size (~218 nm), low polydispersity (PDI 0.164–0.214), and high encapsulation efficiencies (DOX: 49.56 ± 0.15%; siFGF2: 77.66 ± 1.30%). In vitro release studies revealed a robust pH-responsive profile, characterized by sustained stability at physiological pH (7.4) and rapid burst release at acidic endosomal pH (5.5). In MCF-7 and MDA-MB-231 cells, QTPlus-DOX-siFGF2 significantly enhanced cellular uptake, downregulated FGF2 (0.639-fold) and VIM (0.373-fold), and upregulated CASP3 (3.364-fold in siFGF2 group) and BRCA1 (4.041-fold). Flow cytometry showed markedly increased apoptosis (78.5% vs. 42.65% for QTPlus-DOX alone). In the MDA-MB-231 xenograft model, QTPlus-DOX-siFGF2 achieved 65.87% tumor growth inhibition with stable body weights and favorable trends in cardiotoxic biomarkers. Conclusions: These results demonstrate that QTPlus enables effective co-delivery of DOX and siFGF2, producing synergistic antitumor effects through apoptosis induction and suppression of epithelial–mesenchymal transition while improving the safety profile. QTPlus-DOX-siFGF2 represents a promising nanotherapeutic strategy for breast cancer warranting further clinical development. Full article

Fisetin (FIS) is a bioactive flavonoid with antioxidant, anti-inflammatory, and anticancer activity, but its poor aqueous solubility and high lipophilicity limit its therapeutic use. In this study, three-component FIS-loaded mixed micelles based on Poloxamer 407 (P407) or Poloxamer 188 (P188), sodium deoxycholate, and Kolliphor HS15 or Kolliphor ELP were developed and comparatively evaluated. The formulations were prepared by the thin-film hydration method and characterized in terms of physicochemical properties, storage stability, solid-state properties, and in vitro biological activity. All freshly prepared formulations formed nanosized systems with high encapsulation efficiency. Although P188-based micelles showed smaller initial particle sizes, P407-based systems exhibited superior stability after lyophilization and rehydration. Formulations containing Kolliphor ELP showed the most favorable stability profile over 28 days of storage. FT-IR, TG, DSC, and XRPD analyses confirmed successful incorporation of FIS into the polymeric matrix and transformation of the drug into an amorphous or molecularly dispersed state. In vitro studies demonstrated that micellar encapsulation enhanced the cytotoxic activity of FIS against MICH-2 melanoma cells compared with the free compound, while P407-based systems showed a more favorable safety profile toward MRC-5 fibroblasts. These findings indicate that P407-based mixed micelles, particularly those containing Kolliphor ELP, may serve as promising nanocarriers for improving FIS delivery with potential relevance for dermal and anticancer applications. Full article

Background: Rebamipide (REB) is a poorly water-soluble drug with limited ocular bioavailability, necessitating advanced delivery strategies for sustained therapy in dry eye disease. Methods: In the present study, micelle-assisted ocular inserts were developed using non-ionic surfactants to enhance REB solubilization, drug loading, and controlled ocular delivery. The intrinsic solubility of REB in simulated tear fluid (STF, pH 7.4) was evaluated and compared with micellar systems. The formulations were characterized for particle size, polydispersity index, and zeta potential. Ocular inserts were fabricated via UV photopolymerization and evaluated for physicochemical properties, drug content, in vitro drug release, ex vivo permeation, cytocompatibility using SIRC cells, and histopathological analysis. Results: REB exhibited low intrinsic solubility in STF (26.05 ± 1.00 µg/mL), which was significantly enhanced in micellar systems, particularly with Solutol HS 15 (306.71 ± 1.10 µg/mL) and Tween 80 (263.18 ± 1.19 µg/mL). All micellar formulations formed stable nanosized micelles (7.5–15.1 nm) with low polydispersity (PDI < 0.35) and near-neutral zeta potential (−0.08 to −2.81 mV). The prepared ocular inserts showed uniform thickness, weight, and physiological surface pH. Micelle-assisted inserts demonstrated significantly higher drug content (87.40 ± 3.25 to 99.19 ± 2.44 µg/insert) compared to plain REB inserts (21.41 ± 2.28 µg/insert). In- vitro studies revealed sustained drug release over 24 h (92.25 ± 1.64 to 100.50 ± 1.10%), whereas plain inserts showed burst release. Ex vivo permeation studies indicated enhanced drug permeation (up to 77.30 ± 0.34 µg) and improved flux (1.38–8.52 µg/cm²·h) compared to plain REB. Cytocompatibility studies confirmed >90% SIRC cell viability, and histopathological analysis showed no structural damage to corneal tissue. Conclusions: Micelle-assisted ocular inserts, particularly those formulated with Solutol HS 15 and Tween 80, provide a promising platform for sustained, safe, and effective ocular delivery of Rebamipide in the management of dry eye disease. Full article

Background/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p < 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p < 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy. Full article