ABSTRACT Reactive oxygen species (ROS) are critical mediators in pathological conditions, driving development of ROS‐responsive drug delivery systems for enhanced therapeutic outcomes. The structural stability and functionality of biomaterials‐including hydrogels, gelatin, and chitosan—are governed by hydrogen bonding (HB), a fundamental non‐covalent interaction. However, excessive HB can impair therapeutic efficacy by retarding drug release. This review highlights ROS, elevated in pathological states such as inflammation and cancer, as functional triggers for dynamic control over delivery. Under high‐ROS conditions, bioactive compounds like polyphenols and alkaloids exhibit “redox ambivalence,” switching to pro‐oxidant activity and generating ROS in situ. By exploiting ROS's unique chemical reactivity, these compounds can be engineered to disrupt HB networks, inducing structural transformations in drug carriers. Such changes enable spatiotemporally controlled release of incorporated therapeutics, enhancing site‐specific delivery and efficacy. Moreover, integrating ROS‐responsive bioactive compounds improves drug release kinetics while providing synergistic effects, including ROS scavenging and immune modulation. Consequently, this review examines ROS‐mediated disruption of HB within polymeric carriers and bioactive compounds, facilitating controlled therapeutic release at disease sites.
ABSTRACT A promising delivery system is being investigated for better management of a highly neglected disease segment named keratomycosis, using nanoemulsion‐based gels (nanoemulgels). They offer the potential to improve patient compliance, enhance drug penetration and efficacy, extend drug contact time, and reduce side effects compared to traditional eye drops. This investigation focused on the development of a nanoemulsion‐based gel system to facilitate ocular delivery of Natamycin. Drug‐loaded nanoemulgels were prepared using the ultrasonication method. These formulations then underwent assessment for particle size, drug loading capacity, drug release profile, in vitro permeation characteristics, and in vivo ocular irritation potential. The optimized nanoemulsion‐based in situ gel (FNG4) showed superior ex vivo transcorneal permeation, with < 200 nm particle size, +26.3 ± 2.24 mV zeta potential, ∼89% residual drug content, and zero‐order kinetics. It was found to be homogeneous and stable for use. In conclusion, an optimized pH‐sensitive ocular formulation capable of treating keratomycosis along with overcoming the existing shortcomings was successfully developed.
ABSTRACT Psoriasis is a chronic skin disease primarily caused by inflammation, resulting in abnormal growth of epidermal cells that cause skin reddening, scaling, and irritation. Tacrolimus (TAC), a poorly soluble immunosuppressant drug, was used in the current study for the management of psoriasis. Moreover, tea tree oil (TTO) was also utilized as a functional excipient to synergize the efficiency of the drug. Here, nanostructured lipidic carriers (NLCs) were formulated using a high‐shear homogenization method. To ensure a robust and scientifically optimized formulation, a Quality by Design (QbD) approach was implemented to systematically investigate the influence of formulation variables on critical quality attributes and to obtain an optimized nanoformulation. The developed nanocarriers showed 108.65 ±2.4 nm particle size, 0.265±0.028 polydispersity index, and ∼ 23.9 mV zeta potential. Morphological examination revealed the spherical structure of nanoformulations with uniform distribution. Differential scanning colorimeter studies showed the absence of a crystalline state of the drug, when incorporated in the formulation. Furthermore, gel formulations of drug‐embedded NLCs were characterized for pH, viscosity, and spreadability. In vivo model was used to elucidate the higher efficacy of the developed formulation. In this work, different studies highlight the potential of tacrolimus loaded novel gel including the complementary advantages of tea tree oil.
ABSTRACT Sonodynamic therapy (SDT) has emerged as a promising cancer treatment modality owing to its noninvasive nature and deep tissue penetration capability. Beyond direct tumor ablation, SDT can modulate antitumor immunity, which drives the development of high‐performance sonodynamic platforms for precise and potent immunoregulation. In this review, we summarize recent advances in molecular engineering strategies for developing intelligent sonosensitizers capable of orchestrating diverse immunological processes. These advanced platforms promote robust immunogenic cell death through enhanced reactive oxygen species generation, amplify immune activation by mimicking costimulatory signaling or integrating genetically engineered bacteria, enable ultrasound‐triggered and in situ release of immune checkpoint inhibitors through responsive linkers, and potentiate STING signaling via responsive prodrug designs, thereby coordinating innate and adaptive immune responses. In addition, activatable acoustic afterglow probes have been developed for real‐time visualization of immune‐cell activity, tumor immune microenvironment dynamics, and SDT‐induced immunogenic events, providing valuable feedback on therapeutic efficacy. Collectively, this review highlights the molecular design principles, functional mechanisms, and biomedical applications of engineered sonodynamic systems, guiding the development of next‐generation platforms for precision cancer immunotherapy and immune imaging.
ABSTRACT Poor aqueous solubility severely limits the brain delivery of paliperidone palmitate (PP), necessitating formulation strategies. Here, a docking‐guided approach is employed to engineer intranasal mixed micelles for improved intranasal delivery and potential brain targeting. Molecular docking identifies D‐α‐tocopheryl polyethylene glycol succinate (TPGS) as the primary interacting excipient (ΔG = −4.0 kcal mol −1 ), while Tween 80 provides complementary interactions enabling cooperative micellization. The optimized PP‐loaded mixed micelles (PP‐MM), developed via a 3 2 factorial design, exhibit nanoscale size (14.97 ± 0.82 nm), narrow dispersity (PDI 0.270 ± 0.021), and efficient drug loading (4.1 ± 0.27%). The formulation demonstrates markedly enhanced in vitro release (89.3 ± 8.2% vs. 33.8 ± 2.8% at 360 min) and substantially improved ex vivo nasal permeation (66.30 ± 5.32% vs. 21.40 ± 2.21%), achieving a 2.64‐fold increase in steady‐state flux (compared to drug suspension). In vivo pharmacodynamic evaluation shows superior suppression of ketamine‐induced hyperlocomotion (279.16 ± 18 vs. 448.33 ± 21.60 counts) without detectable neurotoxicity, supported by preserved neuronal architecture. Collectively, these findings establish docking‐guided mixed micelle engineering as a robust and translational strategy to enhance solubilization, mucosal transport, and therapeutic efficacy, supporting further investigation of this scalable, non‐invasive platform for intranasal delivery of poorly soluble antipsychotic agents.
