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Quetiapine hemifumarate (QF) delivery to the CNS via conventional formulations is challenging due to poor solubility and lower oral bioavailability (9 %). Similarly, many other second-generation antipsychotics, such as olanzapine, clozapine, and paliperidone, have also shown low oral bioavailability of <50 %. Hence, the present work was intended to formulate QF-loaded biodegradable PLGA-NPs with appropriate surface charge modification through poloxamer-chitosan and investigate its targeting potential on RPMI-2650 cell lines to overcome the limitations of conventional therapies. QF-loaded poloxamer-chitosan-PLGA in-situ gel (QF-PLGA-ISG) was designed using emulsification and solvent evaporation techniques. Developed QF-PLGA-ISG were subjected to evaluation for particle size, PDI, zeta potential, ex-vivo mucoadhesion, entrapment efficiency (%EE), and drug loading, which revealed 162.2 nm, 0.124, +20.5 mV, 52.4 g, 77.5 %, and 9.7 %, respectively. Additionally, QF-PLGA formulation showed >90 % release within 12 h compared to 80 % of QF-suspension, demonstrating that the surfactant with chitosan-poloxamer polymers could sustainably release medicine across the membrane. Ex-vivo hemolysis study proved that developed PLGA nanoparticles did not cause any hemolysis compared to negative control. Further, in-vitro cellular uptake and transepithelial permeation were assessed using the RPMI-2650 nasal epithelial cell line. QF-PLGA-ISG not only improved intracellular uptake but also demonstrated a 1.5-2-fold increase in QF transport across RPMI-2650 epithelial monolayer. Further studies in the EpiNasal™ 3D nasal tissue model confirmed the safety and efficacy of the developed QF-PLGA-ISG formulation with up to a 4-fold increase in transport compared to plain QF after 4 h. Additionally, histological reports demonstrated the safety of optimized formulation. Finally, favorable outcomes of IN QF-PLGA-ISG formulation could provide a novel platform for safe and effective delivery of QF in schizophrenic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known financial conflicts that may have looked to have influenced the research presented in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteosarcoma is the most commonly diagnosed form of bone cancer. It is characterized by a high risk of developing lung metastasis as the disease progresses. Standard treatment includes combination of surgical intervention, chemotherapy and radiotherapy. However, the non-specificity of potent chemotherapeutic agents often leads to major side effects. In this review, we discuss the role of various classes of biomaterials, including both organic as well as inorganic in realizing the local and systemic delivery of therapeutic agents like drugs, radioisotopes and even gene silencing agents to treat osteosarcoma. Biomaterial assisted unconventional therapies such as targeted therapy, nanotherapy, magnetic hyperthermia, gene therapy, photothermal and photodynamic therapies are also being explored. A wide variety of biomaterials including lipids, carbon-based materials, polymers, silica, bioactive glass, hydroxyapatite and metals are designed as delivery systems with the desired loading efficiency, release profile, and on-demand delivery. Among others, liposomal carriers have attracted a great deal of attention due to their capability to encapsulate both hydrophobic and hydrophilic drugs. Polymeric systems have high drug loading efficiency and stability and can even be tailored to achieve desired size and physiochemical properties. Carbon-based systems can also be seen as an upcoming class of therapeutics with great potential in treating different types of cancer. Inorganic materials like silica nanoparticles have high drug payload owing to their mesoporous structure. On the other hand, ceramic materials like bioactive glass and hydroxyapatite not only act as excellent delivery vectors but also participate in osteo-regeneration activity. These multifunctional biomaterials are also being investigated for their theranostic abilities to monitor cancer ablation. This review systematically discusses the vast landscape of biomaterials along with their challenges and respective opportunities for osteosarcoma therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)