Drug Delivery Methods Research Articles

Advancing Ocular Medication Delivery with Nano-Engineered Solutions: A Comprehensive Review of Innovations, Obstacles, and Clinical Impact.

Recent advancements in ocular drug delivery have led to the introduction of a range of nanotechnology-based systems, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, inorganic nanoparticles, niosomes, liposomes, nanosuspensions, dendrimers, nanoemulsions, and microemulsions. These systems enhance drug retention, penetration, bioavailability, and targeted delivery, promising prolonged drug release, and improved patient compliance. However, their interactions with biological systems pose potential toxicity risks, necessitating a careful evaluation of nanoparticle size, shape, surface charge, and coating. Traditional ocular drug delivery methods, like topical applications and injections, face challenges due to anatomical and physiological barriers, leading to frequent dosing and systemic toxicity risks. Nanocarriers offer solutions by improving drug permeation and targeted delivery, yet translating these innovations from research to clinical practice involves overcoming hurdles related to manufacturing scale-up, quality control, regulatory approval, and cost-effectiveness. The quality by design (QbD) framework provides a systematic approach to optimize nanocarrier formulation and process design, ensuring safety and efficacy. Assessing the safety of nanocarriers through in vivo and in vitro studies is crucial for their clinical application. This review explores the use of various nanomedicines in ocular drug delivery, highlighting the current state of ocular medication delivery and considering critical aspects such as scaling up and clinical applications.

Andrographolide sulfonate downregulation of TLR3-TRIF and amelioration of airway inflammation caused by respiratory syncytial virus infection.

Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation. Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1-9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-β (TRIF) were detected via Western blot analysis. RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection. Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.

Hyaluronic Acid Receptor-Mediated Nanomedicines and Targeted Therapy.

Hyaluronic acid (HA) is a naturally occurring polysaccharide found in the extracellular matrix with broad applications in disease treatment. HA possesses good biocompatibility, biodegradability, and the ability to interact with various cell surface receptors. Its wide range of molecular weights and modifiable chemical groups make it an effective drug carrier for drug delivery. Additionally, the overexpression of specific receptors for HA on cell surfaces in many disease states enhances the accumulation of drugs at pathological sites through receptor binding. In this review, the modification of HA with drugs, major receptor proteins, and the latest advances in receptor-targeted nano drug delivery systems (DDS) for the treatment of tumors and inflammatory diseases are summarized. Furthermore, the functions of HA with varying molecular weights of HA in vivo and the selection of drug delivery methods for different diseases are discussed.

Nanozyme-enhanced mitophagy to improve the efficacy of mesenchymal stem cells in myocardial infarction therapy

Mesenchymal stem cell therapy has emerged as a promising approach for the treatment of myocardial infarction. However, the challenge of low cell survival and retention post injection, particularly under the high levels of reactive oxygen species (ROS) and oxidative stress at the infarct site, has hindered their clinical application. Additionally, traditional drug delivery methods, such as intravenous injection, cannot meet the demand for long-term stem cell residence at the infarct site, which is another critical issue that impedes the therapeutic efficacy of stem cells. Herein, we synthesized indocyanine green-enriched Prussian blue nanozyme, called PB@PEI@ICG, which not only possessed remarkable ROS scavenging capability but also exhibited superior fluorescent tracer property. Subsequently, we engineered mesenchymal stem cells (MSCs) with PB@PEI@ICG by co-culture and found that the introduction of the nanozyme significantly enhanced mitophagy by BNIP3 and PINK1 pathways, which in turn promoted ROS scavenging and protected MSCs from cell death induced by the harsh infarct microenvironment. Furthermore, we employed pericardial injection as an alternative delivery method to prolong the residence time of MSCs at the infarct site, enabling real-time tracking via the fluorescence property of the nanozymes. The results demonstrated that PB@PEI@ICG nanozyme could significantly improve the survival and retention of MSCs at the infarct site, thereby enhancing the therapeutic effect for myocardial infarction. In conclusion, this study presents a novel strategy for stem cell therapy in myocardial infarction by using mitophagy-enhancing nanozyme to scavenge ROS for enhancing the therapeutic potential of stem cells.

Isoproterenol induced cardiac hypertrophy: A comparison of three doses and two delivery methods in C57BL/6J mice.

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective β-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

Precision medicine in breast cancer: Targeting molecular subtypes with gold nanoparticle-loaded liposomes

PurposeBreast cancer is a complex disease with several molecular subtypes that respond differently to therapy. This paper describes liposomes loaded with gold nanoparticles as a targeted drug delivery method in the rapidly developing precision breast cancer treatment area. The aim was to investigate the cytotoxicity level and cellular uptake using several breast cancer cell lines and a normal breast cell line. Materials and methodsWe synthesized gold nanoparticles incorporated in liposomes. Nanostructures were incubated with breast cancer cell lines of different subtypes. The analysis included MTT assay, flow cytometry and immunofluorescence. ResultsCell viability varied among different cancer cells. Moreover, the time- and concentration-dependent manner of viability change was observed. The internalization of liposomes with gold nanoparticles and nanoparticles alone determined different results depending on molecular breast cancer subtypes. The luminal B and triple-negative breast cancer cells demonstrated the highest resistance and sensitivity, respectively. The intensity of cells’ interaction with the proposed nanostructures was observed in both cell lines. In this study, we compare the molecular subtypes of breast cancer and discuss how this novel method might improve the therapy success. ConclusionsOur research sheds light on the possibility of new individualized treatments for breast cancer patients, opening the path for better results and a more detailed cancer therapy strategy.

Advancements in Natural Alkaloid-Loaded Drug Delivery Systems for Enhanced Peptic Ulcer Treatment: A Review

Abstract: Peptic ulcers, which damage the gastrointestinal tract lining, are a significant global health issue. The traditional approaches to treating peptic ulcers have poor bioavailability, unstable formulations, and undesirable side effects. Natural alkaloids have garnered increased interest as potential therapeutic agents in recent years due to their diverse pharmacological actions and decreased toxicity profiles. This manuscript summarizes recent progress in natural alkaloids for peptic ulcer treatment, highlighting new drug delivery methods. Natural alkaloids, originating from different plants, have anti-inflammatory, antioxidant, and antibacterial properties, potentially accelerating the healing of peptic ulcers. Moreover, medicines don't always function properly because they degrade too fast, don't dissolve well, and have other problems, such as insufficient bioavailability. Creative liposome delivery systems, microspheres, nanocarriers, and other customized delivery strategies have shown promise in overcoming these barriers. By distributing the medication gradually and precisely, these innovative techniques improve the medication and effectiveness at the ulcer site. As a result, natural ingredients work better and provide better treatment results.

Pretreatment of microneedles enhances passive transdermal administration of pilocarpine and pilocarpine-induced sweat production in humans

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to ∼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

Stimuli-Responsive Nanocomposite Hydrogels for Oral Diseases.

Oral diseases encompassing conditions such as oral cancer, periodontitis, and endodontic infections pose significant challenges due to the oral cavity's susceptibility to pathogenic bacteria and infectious agents. Saliva, a key component of the oral environment, can compromise drug efficacy during oral disease treatment by diluting drug formulations and reducing drug-site interactions. Thus, it is imperative to develop effective drug delivery methods. Stimuli-responsive nanocomposite hydrogels offer a promising solution by adapting to changes in environmental conditions during disease states, thereby enabling targeted drug delivery. These smart drug delivery systems have the potential to enhance drug efficacy, minimize adverse reactions, reduce administration frequency, and improve patient compliance, thus facilitating a faster recovery. This review explores various types of stimuli-responsive nanocomposite hydrogels tailored for smart drug delivery, with a specific focus on their applications in managing oral diseases.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects.

Nitric oxide-generating metallic wires for enhanced metal implants

Metallic implants are integral in modern medicine, offering excellent biocompatibility and mechanical properties. However, implant-related infections pose a major challenge. Current drug delivery methods, such as surface-coated and drug-eluting implants, are limited by finite drug supplies and complex manufacturing steps. Recent approaches like local drug synthesis, including enzyme-prodrug therapies, present innovative solutions but are hampered by the inherent limitations of enzymes as well as complex procedures. Here, we introduce a simpler alternative: using the intrinsic properties of implant materials to activate prodrugs. Through a simple thermal treatment, metallic implants gain catalytic properties to locally generate nitric oxide, an antibacterial agent. Our findings show this treatment is non-toxic to cells, does not affect cell proliferation rates, and effectively inhibits bacterial biofilm formation. This material-driven approach eliminates the need for external chemical or enzymatic interventions, offering a promising solution to prevent implant-related infections and improve patient outcomes in implant medicine.

Ocular Hydrogel Materials and Corresponding Methods of Anterior Segment Drug Delivery: A Review

Ocular conditions have historically proven difficult to treat. Topical eye drops are the primary method of anterior ocular drug delivery but have demonstrated low effectiveness as they require perpetual administration to achieve adequate doses of drug in the target tissue. This can lower patient compliance and increase the risk of side effects, such as systemic toxicity as most of the drug is absorbed through the eye’s natural clearance pathways. Considering this, further development of alternate anterior delivery methods has the potential to improve drug effectiveness, residence times, and bioavailability, as well as reduce systemic toxicity. To this end, the ongoing development of contact lenses, thermogels, nanoparticle delivery systems, as well as mucoadhesive and mucopenetrative properties are being explored. This paper will discuss these developments, as well as their implications in ocular treatment.

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer.

Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach's efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan's mechanism, a topoisomerase I inhibitor, and minocycline's broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier's restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.

Biodistribution and toxicity assessment of gallic acid (GA)-loaded mesoporous silica nanoparticles coated with lipid in male wistar rats: A comprehensive investigation

BackgroundThe Blood-Brain Barrier (BBB), which protects the brain from many medications, is the biggest challenge for researchers testing new neurological treatments. Our research uses lipid bilayer-coated (LB) mesoporous silica nanoparticles (MSN) to increase gallic acid (GA) absorption over the BBB and improve its therapeutic benefits. MethodsThe formulations were characterized using Fourier transform infrared, x-ray diffraction (XRD), transmission electron microscopy, drug release, encapsulation efficiency, loading capacity, process yield, and dynamic light scattering to assess particle size and calculate zeta potential. Our investigation divided male Wistar rats into five groups: control, MSN, GA (20 mg/kg GA), MSN-GA, and LB-MSN-GA. HPLC biodistribution, oxidative stress, and cortical and hippocampal histopathology were also done. Key findingsThis study shows gallic acid can be encapsulated into MSN-GA and LB-MSN-GA nanoparticles with good loading capacities and encapsulation efficiency. Fourier transform infrared spectroscopy (FTIR) and XRD confirmed nanoparticle mesoporousness. The study also indicated that LB-MSN-GA may modify cortical and hippocampal histopathological and biochemical parameters. LB-MSN-GA loading altered GA distribution maps across the cortex and hippocampus. ConclusionGallic acid (GA) transfer via LB-MSN-GA substantially impacts rats' cortex and hippocampus. Therefore, one promising method of drug delivery for the brain is LB-MSN-GA.

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.

Nasal Drug Delivery and Nose-to-Brain Delivery Technology Development Status and Trend Analysis: Based on Questionnaire Survey and Patent Analysis.

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990-2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.

Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood‐brain barrier

AbstractThe blood‐brain barrier (BBB) poses daunting challenges in treating diseases associated with the central nervous system (CNS). Recently, the traditional notion of the absence of the lymphatic system in the brain is evolving. The discovery of the glymphatic system in the brain has stimulated tremendous interest in developing new strategies for the treatment of CNS diseases. Leveraging the glymphatic system for CNS drug delivery may pave a new avenue to circumvent the BBB and achieve efficient drug delivery. The review focuses on the glymphatic system of the brain, discussing potential factors affecting its functions and exploring their connections with the meningeal lymphatic system. Finally, the review provides an overview of the drug delivery methods through the glymphatic system to circumvent BBB and regulate brain immunity. These innovative drug delivery methods may significantly improve drug utilization and create new avenues for the treatment of brain diseases.

A Critical Review on Glycosaminoglycan Derived Polymers as a Novel Drug Delivery System in Tissue Engineering: Recent Advancement and Clinical Application

Glycosaminoglycans (GAGs), natural components of the extracellular matrix, exert significant influence over cellular function and regulate the microenvironment surrounding cells. This characteristic makes them promising targets for therapeutic intervention across a spectrum of diseases. In the realm of medical research, there has been a longstanding quest for precise and targeted drug delivery methods to mitigate adverse effects and enhance the efficacy of treatments for conditions, such as wounds, cancer, and organ disorders. However, implementing a systemic delivery approach, particularly for protein-based therapeutics, poses challenges. Addressing this challenge requires the development of biocompatible materials capable of efficiently encapsulating and releasing therapeutic proteins. GAGs emerge as promising candidates possessing these desirable attributes, given their bioderived nature and ability to modulate biological responses. Within the realm of GAGs, various linear polysaccharides exhibit diverse functionalities and payloads. Notably, hyaluronic acid (HA) and chondroitin sulfate (CS) have been utilized as polysaccharide-based biomaterials for drug delivery, particularly in the treatment of rheumatoid arthritis. Modified HA and CS can self-assemble into micelles or micellar nanoparticles (NPs), enabling precise and controlled drug delivery. This paper explores a range of NP formulations derived from HA and CS, including drug conjugates, polymers, small molecules, polyelectrolyte nanocomplexes (PECs), metals, and nanogels. The versatility of these NP formulations extends to various therapeutic applications, including cancer chemotherapy, gene therapy, photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and immunotherapy. By harnessing the unique properties of HA and CS, these NP-based systems offer promising avenues for advancing therapeutic interventions in diverse clinical settings.

Formulation and evaluation of amoxapine mucoadhesive buccal films

Among innovative drug delivery methods, buccal mucoadhesive systems have been attracting much interest recently because of their capacity to stick to the oral mucosa, stay there, and gradually release their drug content. By improving medication absorption through the oral mucosa and reducing the hepatic first-pass impact, buccal mucoadhesive films can increase the drug's bioavailability and enhance its therapeutic effect. The current study aimed to synthesize the medicine as a buccal bioadhesive film, which reduces the frequency of dosage form administration by releasing the drug at a sufficient concentration over time. Because this formulation is simple to administer and requires no water to swallow, improved patient compliance is one of its benefits. Dissolving profile as investigated in USP dissolving apparatus type 1 using saliva at pH 6.8. The impact of factors such as polymer type, concentration, and release profile of Amoxapine was investigated. The formulation was optimized Based on several evaluation criteria, including drug content and in-vitro drug release. Formulation F6 successfully releases the drug in 7 hours. The stability studies followed ICH recommendations, and the results showed that the optimized formulation was stable. The IR spectra demonstrated the stable qualities of Amoxapine in a mixture of polymers utilized and revealed the absence of interaction between the drug and the selected polymer.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.