Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery.

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs.

Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma.

The present study aimed to prepare solid lipid-based nanoparticles (SLNs) using Precirol® ATO 5 as solid lipid and Poloxamer 188 and Tween 80 as surfactant and co-surfactant respectively, and SLNs-derived gel for sustained delivery, enhanced in-vitro cytotoxicity, enhanced cellular uptake of 5-FU and enhanced permeation of 5-FU across the skin. The 5-FU-loaded SLNs were prepared by the hot melt encapsulation method and converted into SLN-derived gel using a gelling agent (Carbopol 940). The 5-FU-loaded SLNs had a particle size in the range of 76.82±1.48 to 327±4.46 nm, zeta potential between -11.3±2.11 and -28.4±2.40 mV, and entrapment efficiency (%) in range of 63.46±1.13 and 76.08±2.42. The FTIR analysis depicted that there was no chemical interaction between 5-FU and formulation components. Differential scanning calorimetric analysis showed thermal stability of 5-FU in the nanoparticles and powdered X-ray diffraction analysis revealed successful incorporation of 5-FU in nanoparticles. The in-vitro release study of 5-FU-loaded SLNs showed biphasic release behavior with initial burst release followed by sustained release over 48 hr. The 5-FU-loaded SLNs showed a greater cytotoxic effect on skin melanoma (B16F10 cells) and squamous cell carcinoma (A-431 cells) as compared to free 5-FU drug solution after 48 hr. Flow cytometry and fluorescence microscopy displayed enhanced quantitative and qualitative cellular uptake of SLNs. The SLNs formulation showed acceptable safety and biocompatible profile after an acute toxicity study in Wistar rats. Moreover, ex-vivo permeation studies depicted 2.13±0.076 folds enhanced flux of 5-FU-loaded SLN derived gel compared to 5-FU plain gel, and skin retention studies revealed target efficiency (%) 2.54±0.03 of 5-FU-loaded SLN derived gel compared to 5-FU plain gel.

Folate decorated lipid chitosan hybrid nanoparticles of 5-fluorouracil for enhanced anticancer efficacy against colon cancer.

The study aimed to develop folate decorated lipid chitosan hybrid nanoparticles for targeted delivery of 5-fluorouracil in colon cancer by utilizing the overexpressed folate receptors on the surface of HT-29 and HCT 116 cancer cell lines. The developed formulations were prepared by the ionic gelation method with slight modifications. The developed formulations exhibited spherical morphology, smaller particle size (158 to 225 nm), zeta potential (32.24 to 35.95 mV), PDI (0.19 to 0.35), and high encapsulation efficiency (85.3 % to 94.2 %) with optimal physicochemical characteristics. The in vitro release showed a biphasic release pattern with an initial burst release followed by a sustained release for 48 h. Moreover, the in vitro cell line study revealed that FA-CLPN-2 exhibited an enhanced cellular uptake and greater cytotoxic effect in HT-29 and HCT 116 cell lines compared to non-targeted CLPN-2 and free drug solution due to the folate receptor facilitated endocytosis process. The in vivo toxicity study revealed the safety and biocompatibility of the developed formulations in biological systems. The stability study demonstrates the stability of the developed formulations. Overall, these results suggest that the folate decorated lipid chitosan hybrid nanoparticles could be used as a potential delivery system for tumor-targeted therapy with reduced side effects.

Network Meddling Detection Using Machine Learning Empowered with Blockchain Technology.

The study presents a framework to analyze and detect meddling in real-time network data and identify numerous meddling patterns that may be harmful to various communication means, academic institutes, and other industries. The major challenge was to develop a non-faulty framework to detect meddling (to overcome the traditional ways). With the development of machine learning technology, detecting and stopping the meddling process in the early stages is much easier. In this study, the proposed framework uses numerous data collection and processing techniques and machine learning techniques to train the meddling data and detect anomalies. The proposed framework uses support vector machine (SVM) and K-nearest neighbor (KNN) machine learning algorithms to detect the meddling in a network entangled with blockchain technology to ensure the privacy and protection of models as well as communication data. SVM achieves the highest training detection accuracy (DA) and misclassification rate (MCR) of 99.59% and 0.41%, respectively, and SVM achieves the highest-testing DA and MCR of 99.05% and 0.95%, respectively. The presented framework portrays the best meddling detection results, which are very helpful for various communication and transaction processes.

IoMT-Based Osteosarcoma Cancer Detection in Histopathology Images Using Transfer Learning Empowered with Blockchain, Fog Computing, and Edge Computing.

Bone tumors, such as osteosarcomas, can occur anywhere in the bones, though they usually occur in the extremities of long bones near metaphyseal growth plates. Osteosarcoma is a malignant lesion caused by a malignant osteoid growing from primitive mesenchymal cells. In most cases, osteosarcoma develops as a solitary lesion within the most rapidly growing areas of the long bones in children. The distal femur, proximal tibia, and proximal humerus are the most frequently affected bones, but virtually any bone can be affected. Early detection can reduce mortality rates. Osteosarcoma's manual detection requires expertise, and it can be tedious. With the assistance of modern technology, medical images can now be analyzed and classified automatically, which enables faster and more efficient data processing. A deep learning-based automatic detection system based on whole slide images (WSIs) is presented in this paper to detect osteosarcoma automatically. Experiments conducted on a large dataset of WSIs yielded up to 99.3% accuracy. This model ensures the privacy and integrity of patient information with the implementation of blockchain technology. Utilizing edge computing and fog computing technologies, the model reduces the load on centralized servers and improves efficiency.

Core-shell Pluronic F127/chitosan based nanoparticles for effective delivery of methotrexate in the management of rheumatoid arthritis.

This study was designed to improve oral bioavailability of the methotrexate (MTX) by sustaining its release profile and integration into core-shell polymeric nanoparticles. The self-micellization and ionotropic gelation technique was employed which resulted into spherical shaped nanoparticles (181-417 nm) with encapsulation efficiency of 80.14% to 85.54%. Furthermore, Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry analyses were carried out to investigate physicochemical and thermal stability of the produced engineered core shell nanoparticles of the methotrexate. . Entrapment of drug in polymeric core was confirmed by X-ray diffraction analysis. In-vitro sustained release behavior of nanoparticles was observed at pH 6.8 for 48 h while low drug release was observed at pH 1.2 due to pH-responsive nature of Pluronic F127. Acute toxicity study confirmed safety and biocompatible profile of nanoparticles. MTX loaded polymeric nanoparticles ameliorated the pharmacokinetic profile (8 folds greater half-life, 6.26 folds higher AUC0-t and 3.48 folds higher mean residence time). In vivo study conducted in rat model depicted the improved therapeutic efficacy and healing of arthritis through MTX loaded polymeric nanoparticles, preferentially attributable to high accretion of MTX in the inflamed site. In conclusion, MTX loaded polymeric nanoparticles is an attractive drug delivery strategy for an effective management and treatment of rheumatoid arthritis.

Blockchain-Based Smart Home Networks Security Empowered with Fused Machine Learning.

Security and privacy in the Internet of Things (IoT) other significant challenges, primarily because of the vast scale and deployment of IoT networks. Blockchain-based solutions support decentralized protection and privacy. In this study, a private blockchain-based smart home network architecture for estimating intrusion detection empowered with a Fused Real-Time Sequential Deep Extreme Learning Machine (RTS-DELM) system model is proposed. This study investigates the methodology of RTS-DELM implemented in blockchain-based smart homes to detect any malicious activity. The approach of data fusion and the decision level fusion technique are also implemented to achieve enhanced accuracy. This study examines the numerous key components and features of the smart home network framework more extensively. The Fused RTS-DELM technique achieves a very significant level of stability with a low error rate for any intrusion activity in smart home networks. The simulation findings indicate that this suggested technique successfully optimizes smart home networks for monitoring and detecting harmful or intrusive activities.

Living walls enhancing the urban realm: a review.

In the current Anthropocene epoch, globalization and urbanization have adversely affected our environment causing global warming. To counter the adverse effects of global warming, research is being conducted into many innovative technologies to identify viable solutions. This paper will focus on one such solution, Living walls and how the built form is enriched by the environmental and psychological benefits provided by Living walls. Buildings with Living walls have lively surroundings which enhance the urban fabric. This review paper shall elaborate on the effects of Living walls on the built environment in the urban realm and analyze how Living walls improve the urban fabric in terms of activity and behavior pattern, streetscape and building frontage.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin.

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08-206.4 ± 2.26 nm, zeta potential was -17.8 ± 1.26 to -24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

Evaluation of the anti-inflammatory, antioxidant, and cytotoxic potential of Cardamine amara L. (Brassicaceae): A comprehensive biochemical, toxicological, and in silico computational study.

Introduction: Cardamine amara L. (Brassicaceae) is an important edible plant with ethnomedicinal significance. This study aimed at evaluating the phytochemical composition, anti-inflammatory, antioxidant and cytotoxicity aspects of the hydro-alcoholic extract of C. amara (HAECA). Methods: The phytochemical composition was evaluated through total phenolic contents (TPC), total flavonoid contents (TFC) determination and UPLC-QTOF-MS profiling. Anti-inflammatory evaluation of HAECA was carried out through the carrageenan induced paw edema model. Four in vitro methods were applied in the antioxidant evaluation of HAECA. MTT assay was used to investigate the toxicity profile of the species against human normal liver cells (HL7702), human liver cancer cell lines (HepG2) and human breast cancer cell lines (MCF-7). Three major compounds (Gentisic acid, skullcapflavone and conidendrine) identified in UPLC-Q-TOF-MS analysis were selected for in silico study against cyclooxygenase (COX-I and COX-II). Results and Discussion: The findings revealed that HAECA is rich in TPC (39.32 ± 2.3 mg GAE/g DE) and TFC (17.26 ± 0.8 mg RE/g DE). A total of 21 secondary metabolites were tentatively identified in UPLC-Q-TOF-MS analysis. In the MTT cytotoxicity assay, the extract showed low toxicity against normal cell lines, while significant anticancer activity was observed against human liver and breast cancer cells. The carrageenan induced inflammation was inhibited by HAECA in a dose dependent manner and showed a marked alleviation in the levels of oxidative stress (catalase, SOD, GSH) and inflammatory markers (TNF-α, IL-1ß). Similarly, HAECA showed maximum antioxidant activity through the Cupric reducing power antioxidant capacity (CUPRAC) assay (31.21 ± 0.3 mg TE/g DE). The in silico study revealed a significant molecular docking score of the three studied compounds against COX-I and COX-I. Conclusively the current study encourages the use of C. amara as a novel polyphenolic rich source with anti-inflammatory and antioxidant potential and warrants further investigations on its toxicity profile.

Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein.

The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced in vitro dissolution. Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45-762.8±2.05 nm and -22.4±0.55-31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier (Maltodextrin) followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.

Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma.

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81-187.13 ± 4.15 nm), colloidal stability (-13.27 ± 0.04 to -32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01-79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer-Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer efficacy.

AIMS: The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line. MATERIALS AND METHODS: The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells. SIGNIFICANT FINDINGS: Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents. SIGNIFICANCE: The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization.

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50-148µm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting.

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.

AIMS: The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. MATERIALS AND METHODS: Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. KEY FINDINGS: A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. SIGNIFICANCE: The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.

Co-Delivery of Curcumin and Cisplatin to Enhance Cytotoxicity of Cisplatin Using Lipid-Chitosan Hybrid Nanoparticles.

BACKGROUND: Lipid-polymer hybrid nanoparticles (LPHNP) are suitable for co-delivery of hydrophilic and lipophilic drugs. The structural advantages of polymers and biomimetic properties of lipids enable higher encapsulation of drugs and controlled release profile. Lipid-polymer hybrid nanoparticles have been prepared for co-delivery of curcumin and cisplatin for enhanced cytotoxicity against ovarian cancer. MATERIAL AND METHODS: Chitosan, cisplatin, curcumin, Lipoid S75 were selected as structural components and ionic gelation method was used for preparation of LPHNPs. Nanoparticles were formed via ionic interaction of positively charged chitosan and negatively charged lipid. RESULTS: The optimized nanoparticles were of 225 nm with cationic charge. The encapsulation efficiency was greater than 80% with good drug loading. The drug release profile showed controlled release behavior of both curcumin and cisplatin simultaneously and the absence of burst release. The in vitro therapeutic efficacy and cellular association was evaluated using A2780 ovarian cell lines. To further investigate therapeutic efficacy, we developed 3D spheroids as tumor model to mimic the in vivo conditions. The cytotoxicity and uptake of co-loaded LPHNPs were evaluated on 3D spheroids and results indicated increased chemosensitization and enhanced therapeutic efficacy of co-loaded LPHNPs. CONCLUSION: Lipid-polymer hybrid nanoparticles could be a suitable platform for co-delivery of curcumin and cisplatin for enhanced cytotoxic effect on ovarian cell lines.