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Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design-related insights.

Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways for active targeting of anticancer therapy, delivery of DNA or RNA materials, and use as a diagnostic imaging agent. This review will provide an update on recent key advancements in design, synthesis, and bioactivity evaluation as well as discussion of future clinical possibilities of LPHNPs.

Nanoparticle-based drug delivery presents a promising solution in enhancing therapies for neurological diseases, particularly cognitive impairment. These nanoparticles address challenges related to the physicochemical profiles of drugs that hinder their delivery to the central nervous system (CNS). Benefits include improved solubility due to particle size reduction, enhanced drug penetration across the blood-brain barrier (BBB), and sustained release mechanisms suitable for long-term therapy. Successful application of nanoparticle delivery systems requires careful consideration of their characteristics tailored for CNS delivery, encompassing particle size and distribution, surface charge and morphology, loading capacity, and drug release kinetics. Literature review reveals three main types of nanoparticles developed for cognitive function enhancement: polymeric nanoparticles, lipid-based nanoparticles, and metallic or inorganic nanoparticles. Each type and its production methods possess distinct advantages and limitations. Further modifications such as coating agents or ligand conjugation have been explored to enhance their brain cell uptake. Evidence supporting their development shows improved efficacy outcomes, evidenced by enhanced cognitive function assessments, modulation of pro-oxidant markers, and anti-inflammatory activities. Despite these advancements, clinical trials validating the efficacy of nanoparticle systems in treating cognitive defects are lacking. Therefore, these findings underscore the need for researchers to expedite clinical testing to provide robust evidence of the potential of nanoparticle-based drug delivery systems.

Ikra Nurohman,1,2 Anis Yohana Chaerunisaa,2 Gofarana Wilar,3 Garnadi Jafar,4 Cecep Suhandi,2 Sriwidodo Sriwidodo2 1Doctoral Program of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 4Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Bhakti Kencana, Bandung, 40614, IndonesiaCorrespondence: Sriwidodo Sriwidodo, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia, Tel +62 816-4204-079, Email sriwidodo@unpad.ac.idBackground and Objective: Curcumin exhibits potent antioxidant activity beneficial for the prevention of various degenerative diseases; however, its highly lipophilic nature and susceptibility to degradation limit its solubility and physicochemical stability. To address these limitations, curcumin was formulated into nanostructured lipid carriers (NLCs), a lipid-based colloidal delivery system composed of solid and liquid lipids stabilized by surfactants. In this study, sacha inchi oil, a natural oil rich in omega-3 and other unsaturated fatty acids, was investigated as a novel liquid lipid component to improve lipid matrix structure and drug accommodation.Methods: Curcumin-loaded NLCs were prepared using the hot homogenization method followed by probe sonication. Curcumin served as the active compound, while solid lipids (oleum cacao, glyceryl behenate (Compritol® 888 ATO), or glyceryl palmitostearate (Precirol® ATO 5)), sacha inchi oil as the liquid lipid, and surfactants (Tween 80, Poloxamer, or a Tween 80–Span 80 combination) were used. The resulting NLCs were characterized in terms of particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), physicochemical properties (FTIR, DSC, XRD), morphology, and in vitro release behavior.Results: Physicochemical analyses confirmed successful incorporation of curcumin into the lipid matrix without undesirable interactions. Among the tested formulations, CaTS2 (oleum cacao 4.5%, sacha inchi oil 1%, Tween 80 12.5%, Span 80 1%, and curcumin 0.1%) demonstrated the most favorable characteristics, with a particle size of 95.50 ± 0.87 nm, PDI of 0.119 ± 0.157, and ZP of − 22.30 ± 0.98 mV. Entrapment efficiency reached 97.24% and morphological analysis showed predominantly spherical particles. In vitro release exhibited a biphasic pattern, consisting of an initial burst followed by sustained release up to 480 min. Kinetic modeling revealed that CaTS2 followed the Korsmeyer–Peppas model (R2 = 0.793; n = 0.301), consistent with Fickian diffusion, whereas pure curcumin followed the Higuchi model (R2 = 0.819). The similarity factor (f2 = 29.04) indicated a distinctly different release profile between the two systems.Conclusion: Sacha inchi oil–based nanostructured lipid carriers were successfully developed and demonstrated favorable physicochemical characteristics, supporting their potential as a stable delivery system for curcumin.Keywords: curcumin, nanostructured lipid carriers, sacha inchi oil, drug delivery, lipid-based nanoparticle

Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy. Cancer is a prevalent and lethal ailment that has a considerable social and economic impact globally. Despite notable progress in recent years, immunotherapy poses a challenge due to the limited response of a subset of cancer patients in the clinic. Lipid‐based nanoparticles (lipid‐NPs) have garnered significant interest for their capacity to enhance the effectiveness of cancer immunotherapy while minimizing toxic side effects. This review provides a summary of the physicochemical properties, applications, advantages, and disadvantages of various lipid‐NP types. Moreover, we provide an overview on how lipid‐NPs may broaden the therapeutic scope of cancer immunotherapy, using as example how lipid‐based NPs delivery of agonists targeting stimulators of interferon genes augments immunotherapy.

Lipid-based drug-delivery systems have evolved from micro- to nano-scale, enhancing the efficacy and therapeutic applications of these delivery systems. Production of lipid-based pharmaceutical nanoparticles is categorized into top-down (fragmentation of particulate material to reduce its average total dimensions) and bottom-up (amalgamation of molecules through chemical interactions creating particles of greater size) production methods. Selection of the appropriate method depends on the physiochemical properties of individual entities within the nanoparticles. The production method also influences the type of nanoparticle formulations being produced. Liposomal formulations and solid-core micelles are the most widely utilized lipid-based nanoparticles, with surface modifications improving their therapeutic outcomes through the production of long-circulating, tissue-targeted and/or pH-sensitive nanoparticles. More recently, solid lipid nanoparticles have been engineered to reduce toxicity toward mammalian cells, while multifunctional lipid-based nanoparticles (i.e., hybrid lipid nanoparticles) have been formulated to simultaneously perform therapeutic and diagnostic functions. This article will discuss novel lipid-based drug-delivery systems, outlining the properties and applications of lipid-based nanoparticles alongside their methods of production. In addition, a comparison between generations of the lipid-based nano-formulations is examined, providing insight into the current directions of lipid-based nanoparticle drug-delivery systems.

Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy. Graphical Abstract

Cisplatin is a chemotherapeutic agent that causes the irreversible death of auditory sensory cells, leading to hearing loss. Local administration of cytoprotective drugs is a potentially better option co-therapy for cisplatin, but there are strong limitations due to the difficulty of accessing the inner ear. The use of nanocarriers for the efficient delivery of drugs to auditory cells is a novel approach for this problem. Solid lipid nanoparticles (SLNs) are biodegradable and biocompatible nanocarriers with low solubility in aqueous media. We show here that stearic acid-based SLNs have the adequate particle size, polydispersity index and ζ-potential, to be considered optimal nanocarriers for drug delivery. Stearic acid-based SLNs were loaded with the fluorescent probe rhodamine to show that they are efficiently incorporated by auditory HEI-OC1 (House Ear Institute-Organ of Corti 1) cells. SLNs were not ototoxic over a wide dose range. Glucocorticoids are used to decrease cisplatin-induced ototoxicity. Therefore, to test SLNs’ drug delivery efficiency, dexamethasone and hydrocortisone were tested either alone or loaded into SLNs and tested in a cisplatin-induced ototoxicity in vitro assay. Our results indicate that the encapsulation in SLNs increases the protective effect of low doses of hydrocortisone and lengthens the survival of HEI-OC1 cells treated with cisplatin.

Vitiligo, a chronic autoimmune disorder characterized by the presence of depigmented skin patches, remains a therapeutic challenge due to its multifactorial pathogenesis and the absence of highly effective treatment options. Although the exact etiology of vitiligo is not fully understood, factors such as genetic factors, oxidative stress, autoimmunity, and inflammation are implicated in the destruction of melanocytes. Current therapeutic strategies primarily focus on modulating immune responses and alleviating oxidative stress. Conventional treatments, including topical corticosteroids, phototherapy, and immunosuppressive agents, often exhibit limited efficacy and are associated with significant side effects, limiting their long-term application. In recent years, nanotechnology has emerged as a transformative approach in drug delivery systems, offering precise targeting, enhanced drug bioavailability, and minimized systemic toxicity. Nanocarrier-based systems especially lipid-based nanoparticles (LNPs) effectively address critical barriers in vitiligo treatment, such as poor drug solubility, rapid degradation, and inadequate skin penetration. Moreover, controlled drug release mechanisms offered by LNPs ensure sustained therapeutic drug levels at the target site, improving efficacy and reducing the frequency of administration. This review provides an overview of vitiligo, its pathogenesis, and the limitations of conventional treatments while highlighting recent advancements in LNPs-based drug delivery systems as a promising strategy for the effective management of vitiligo.