Drug Delivery Research Articles

Bio-inspired multifunctional and reusable LiP@MFO-GO and LiP@MFO-Chit hybrid enzyme complexes for efficient degradation of melanin

Melanin is a complex brown pigment, primarily responsible for the skin pigmentation. Therefore, cosmetic industries have always been in search of potent oxidative enzymes useful for melanin degradation, and to promise a fair complexion after using their products. In the present study, lignin peroxidase from Pseudomonas fluorescence LiP-RL5 isolate has been immobilized on super-paramagnetic nanoparticles to enhance its stability and reusability. The chitosan coated enzyme-nanomaterial complex (LiP@MFO-Chit) showed higher melanin decolorization (47.30 ± 2.3 %) compared to the graphene oxide coated nanoparticles (LiP@MFO-GO) (41.60 ± 1.6 %). Synthesized enzyme nanoparticle complexes showed microbicidal effect on skin infection causing pathogen, Pantoea agglomerans with an inhibitory zone of 6.0 ± 0.9 mm and 250 µg/100 µl minimum inhibitory concentration, and a 7.0 ± 1.5 mm zone and 170 µg/100 µl MIC for LiP@MFO-GO and LiP@MFO-Chit, respectively. Antioxidant potential of LiP@MFO-Chit and LiP@MFO-GO nano-conjugates showed a substantial DPPH scavenging activity of 75.7 % and 88.3 %, respectively. Therefore, LiP-nanoparticle hybrid complexes analyzed in this study are not only effective as skin whitening agents but they are potential molecules against various microbial skin infections as well as useful for different other biomedical applications like biorefinery, drug delivery, and dermatology, etc.

Maleic Anhydride-Derived Copolymers Conjugated with Beta-Lactam Antibiotics: Synthesis, Characterization, In Vitro Activity/Stability Tests with Antibacterial Studies

The synthesis and characterization of biocompatible three different maleic anhydride co-polymer conjugated with two different beta-lactam antibiotics at in vitro conditions were conducted. The polymer–drug conjugates were synthesized by coupling β-lactam antibiotics via amide bonds to the copolymer. In this work, six different drug-functionalized maleic anhydride copolymers (DFMACs) were synthesized by the chemical conjugation method. This method is based on the ring-opening reaction of the anhydride ring of the copolymer to form an amide bond linking the drug. The synthesized DFMACs were characterized by 1H NMR and FTIR/ATR spectroscopies and analyses were carried out by UV/VIS spectroscopy and Zeta-sizer instrument in detail with consecutive antibacterial tests. The existence of a newly formed amide covalent bond between the drug and the copolymer chains was confirmed by 1H NMR and FTIR/ATR studies. This is the first report on the application of the selected branched biodegradable polymeric matrices for the covalent conjugation of ampicillin and cefalexin. Optimum stability and activity conditions for the synthesized DFMACs were determined. Analyses were conducted under in vitro conditions including varying pH values and simulated body fluids as a function of time to obtain new drug delivery system candidates for the two different antibiotics.

Drag force on a microrobot propelled through blood

Controlling microrobot locomotion in vessels and capillaries is crucial for precise drug delivery and minimally invasive surgeries. However, this is challenging due to the complex interactions with red blood cells (RBCs) and the difficulty navigating within the dense environment. Here, we construct a numerical framework to evaluate the relative resistance coefficient (Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document}) of a microrobot propelled through RBC suspensions. Our experiments validate the numerical results. We find that Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document} increases for smaller microrobots and higher hematocrit levels, while magnetic force strength weakly impacts Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document}. Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document} is smaller than the resistance coefficient of a macroscale robot estimated from the apparent viscosity of the RBC suspension. The aspect ratio of a prolate ellipsoidal microrobot influences Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document} along its long-axis direction. Additionally, machine learning accurately predicts Cr*\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${C}_{{{{{{{{\\rm{r}}}}}}}}}^{* }$$\\end{document}. These insights could enhance the design and control of microrobots for medical applications.

Polydopamine-Coated Zn-MOF-74 Nanocarriers: Versatile Drug Delivery Systems with Enhanced Biocompatibility and Cancer Therapeutic Efficacy

Polydopamine-Coated Zn-MOF-74 Nanocarriers: Versatile Drug Delivery Systems with Enhanced Biocompatibility and Cancer Therapeutic Efficacy

Innovating Leishmaniasis Treatment: A Critical Chemist's Review of Inorganic Nanomaterials.

Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterials─including size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.

ROS–Responsive Ferrocenyl Amphiphilic PAMAM Dendrimers for On–Demand Delivery of siRNA Therapeutics to Cancer Cells

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers, Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover, Fc-C8-AmD 8A also integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.

Cutting-edge Approach of Carbon Nanostructures: Targeted Drug Delivery to Central Nervous System.

Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the bloodbrain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.

Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution.

Controlled drug delivery technology has matured for more than 70 years, starting from a twice-a-day oral formulation to 6 month long-acting injectable formulations. Further technological advances require superior formulations to treat various diseases more efficiently. Developing future formulations with practical innovations for treating existing and new diseases necessitates our continued efforts to overcome at least three main hurdles. They include (i) drug delivery with reduced side effects, (ii) long-term treatment of chronic diseases, and (iii) the overcoming of biological barriers. Such efforts start with the improved ability to accurately test drug delivery efficacy using proper controls. Future development can be aided by artificial intelligence if used properly. The next revolution of drug delivery systems will be augmented if implementation is given equal weight as discovery. Such a process can be accelerated with the systemic revamp of the research funding structure and cultivating a new generation of scientists who can think differently.

Investigation of the size and shape of nano-microcarriers for targeted drug delivery to atherosclerotic plaque in ischemic stroke prevention

Recognizing the significance of drug carriers in the treatment of atherosclerotic plaque is crucial in light of the worldwide repercussions of ischemic stroke. Conservative methodologies, specifically targeted drug delivery, present encouraging substitutes that mitigate the hazards linked to invasive procedures. With the intention of illuminating their considerable significance and prospective benefits, this study examines the impact of the geometry and dimensions of drug-loaded nano-microcarriers on atherosclerotic plaque. The research utilizes a finite element approach to simulate the motion and fluid dynamics of nano-microcarriers loaded with drugs within the carotid arteries. Carriers are available in a variety of shapes and sizes to accommodate patient-specific geometries, pulsatile fluid flow, and non-Newtonian blood properties. Optimization of drug delivery is achieved through the examination of carrier interaction with the inner wall. The results demonstrated that the interaction data between particles and the inner wall of atherosclerotic plaques exhibits micro- and nanoscale patterns that are distinct. Symmetric plaques demonstrate that nanoparticles with a 0.4 shape factor and diameters below 200 nm show the highest interaction rate. Conversely, larger particles (200 and 500 nm) with shape factors of 1 demonstrate comparatively elevated interaction rates. The optimal shape factor for drug-loaded microparticles has been determined to be one, and the number of interactions increases as the diameter of the nanoparticles increases, with a significant increase observed at a shape factor of one. Asymmetric plaques exhibit the maximum interaction rates among particles that have a shape factor of 0.4 and have diameters smaller than 500 µm. The findings establish a foundation for novel therapeutic strategies, establishing nano-microparticles as auspicious contenders for accurate and efficacious drug delivery systems that inhibit plaque proliferation.

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl LewisA motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold–like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl LewisA antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.

Advancements in Iron Oxide Nanoparticles for Multimodal Imaging and Tumor Theranostics.

The emergence of nanomedicine offers renewed promise in the diagnosis and treatment of diseases. Due to their unique physical and chemical properties, iron oxide nanoparticles (IONPs) exhibit widespread application in the diagnosis and treatment of various ailments, particularly tumors. IONPs have magnetic resonance (MR) T1/T2 imaging capabilities due to their different sizes. In addition, IONPs also have biocatalytic activity (nanozymes) and magnetocaloric effects. They are widely used in chemodynamic therapy (CDT), magnetic hyperthermia treatment (MHT), photodynamic therapy (PDT), and drug delivery. This review outlines the synthesis, modification, and biomedical applications of IONPs, emphasizing their role in enhancing diagnostic imaging (including single-mode and multimodal imaging) and their potential in cancer therapies (including chemotherapy, radiotherapy, CDT, and PDT). Furthermore, we briefly explore the challenges in the clinical application of IONPs, such as surface modification and protein adsorption, and put forward opinions on the clinical transformation of IONPs.

Long circulating liposomal platform utilizing hydrophilic polymer-based surface modification: preparation, characterisation, and biological evaluation

Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.

Supramolecularly-Cross-Linked Nanogel Assemblies for On-Demand, Ultrasound-Triggered Chemotherapy.

Stimulating the release of small nanoparticles (NPs) from a larger NP via the application of an exogenous stimulus offers the potential to address the different size requirements for circulation versus penetration that hinder chemotherapeutic drug delivery. Herein, we report a size-switching nanoassembly-based drug delivery system comprised of ultrasmall starch nanoparticles (SNPs, ∼20-50 nm major size fraction) encapsulated in a poly(oligo(ethylene glycol) methyl ether methacrylate) nanogel (POEGMA, ∼150 nm major size fraction) cross-linked via supramolecular PEG/α-cyclodextrin (α-CD) interactions. Upon heating the nanogel using a non-invasive, high-intensity focused ultrasound (HIFU) trigger, the thermoresponsive POEGMA-CD nanoassemblies are locally de-cross-linked, inducing in situ release of the highly penetrative drug-loaded SNPs. HIFU triggering increased the release of nanoassembly-loaded DOX from 17 to 37% after 3 h, a result correlated with significantly more effective tumor killing relative to nanoassemblies in the absence of HIFU or drug alone. Furthermore, 1.5× more total fluorescence was observed inside a tumor spheroid when nanoassemblies prepared with fluorophore-labeled SNPs were triggered with HIFU relative to the absence of HIFU. We anticipate this strategy holds promise for delivering tunable doses of chemotherapeutic drugs both at and within a tumor site using a non-invasive triggering approach.

Ambient Moisture-Driven Self-Powered Iontophoresis Patch for Enhanced Transdermal Drug Delivery.

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80V and a short-circuit current of 11.65µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration

Despite numerous studies on chondrogenesis, the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Reversible Light-Triggered Stretching of Small-Molecule Photochromic Organic Nanoparticles.

Functional organic nanomaterials are nowadays largely spread in the field of nanomedicine. In situ modulation of their morphology is thus expected to considerably impact their interactions with the surroundings. In this context, photoswitchable nanoparticles that are manufactured, amenable to extensive disassembling upon illumination in the visible, and reversible reshaping under UV exposure. Such reversibility turns to be strongly impaired for photochromic nanoparticles in close contact with a substrate. In situ atomic force microscopy investigations at the nanoscale actually reveal progressive disintegration of the organic nanoparticles under successive UV-vis cycles of irradiation, in the absence of intrinsic elastic forces. These results point out the dramatic interactions exerted by surfaces on the cohesion of non-covalently bonded organic nanoparticles. They invite to harness such systems, often used as biomarkers, to also serve as photoactivatable drug delivery nanocarriers.

Terpene-based novel invasomes: pioneering cancer treatment strategies in traditional medicine.

Health care workers have faced a significant challenge because of the rise in cancer incidence around the world during the past 10 years. Among various forms of malignancy skin cancer is most common, so there is need for the creation of an efficient and safe skin cancer treatment that may offer targeted and site-specific tumor penetration, and reduce unintended systemic toxicity. Nanocarriers have thus been employed to get around the issues with traditional anti-cancer drug delivery methods. Invasomes are lipid-based nanovesicles having small amounts of terpenes and ethanol or a mixture of terpenes and penetrate the skin more effectively. Compared to other lipid nanocarriers, invasomes penetrate the skin at a substantially fasterrate. Invasomes possess a number of advantages, including improved drug effectiveness, higher compliance, patient convenience, advanced design, multifunctionality, enhanced targeting capabilities, non-invasive delivery methods, potential for combination therapies, and ability to overcome biological barriers,. These attributes position invasomes as a promising and innovative platform for thefuture of cancer treatment. The current review provides insights into invasomes, with a fresh organizational scheme and incorporates the most recent cancer research, including their composition, historical development and methods of preparation, the penetration mechanism involving effect of various formulation variables and analysis of anticancer mechanism and the application of invasomes.

Rosmarinic acid-grafted gelatin Nanogels for efficient Diquafosol delivery in dry eye disease therapy

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the production of ROS, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

Fabrication and characterization of prednisolone-loaded chitosan and oxidized sodium alginate hydrogel for drug delivery and its biological applications

Fabrication and characterization of prednisolone-loaded chitosan and oxidized sodium alginate hydrogel for drug delivery and its biological applications

Berberine and berberine nanoformulations in cancer therapy: Focusing on lung cancer.

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.