Drug Delivery Research Articles

Formulation and in-vitro permeation kinetic studies of β-cyclodextrin complexed ketoconazole drug capped silver nanoparticles

Background: Invasive fungal infections are a growing global crisis due to environmental shifts and growing vulnerable populations. Pathogenic fungi that infect humans are developing resistance against all approved systemic antifungal drugs. Topical drug delivery systems provide a non-invasive way to distribute therapeutic substances directly to the site of action. Ketoconazole (KZ) is a BCS Class II broad-spectrum drug that is used to treat and prevent fungal infections in which Trichophyton rubrum is the main causative agent.Materials and Methods: The present study utilizes an in-vitro model in which KZ is complexed with β-CD and then capped with AgNPs to formulate a cream and evaluated for the underlying mechanisms and amount of improved passive penetration. The formulated cream is characterized for physiochemical evaluation, Fourier transform infrared spectroscopy (FTIR), kinetic studies indicating the effective stability and encapsulation of the composite.Results: The prepared sample was evaluated in terms of its appearance, drug content, spreadability, and viscosity. Drug diffusion through the dialysis membrane, and the findings showed the β-CD-KZ-AgNPs formulation had a significantly higher permeability than KZ alone and followed first-order kinetics with an anomalous release pattern. The higher solubility and stability of β-CD and nano-sized AgNPs resulted in improved penetration. This study investigates that β-CD-capped AgNPs can significantly enhance KZ passive penetration and diffusion, providing a potentially useful nanocarrier technology for antifungal treatment.Conclusion: Enhancing the passive permeation and diffusion characteristics of KZ on β-Cyclodextrin (β-CD)-capped silver nanoparticles (AgNPs) presents a viable approach for enhancing drug delivery efficiency.

Efficacy and safety of transhepatic arterial chemoembolization with drug-loaded microspheres in unresectable primary liver cancer

BACKGROUND Transhepatic arterial chemoembolization (TACE), as a local treatment, has been widely used in the treatment of unresectable liver cancer. The introduction of drug carrier microspheres has brought new hope for the therapeutic effect of TACE. Microspheres can realize the slow release and directional delivery of drugs, reduce systemic toxicity and improve local curative effect. AIM To compare the effectiveness of traditional transcatheter arterial chemoembolization against microsphere-assisted transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma that is incurable. METHODS We searched the PubMed, Embase, Cochrane Library, and CNKI databases for clinical trials of drug-luting beads TACE (DEB-TACE) vs conventional TACE (cTACE) for the treatment of unresectable liver cancer. We screened references based on inclusion and exclusion criteria and then selected valid data for meta-analysis using RevMan 53 software. The complete response (CR) rate, partial response (PR) rate, postoperative stable disease (SD) rate, and 6-month and 12-month survival rates were compared. RESULTS A total of 12 articles were included, including 1177 patients, 519 of whom received DEB-TACE and 658 of whom received cTACE. The CR rate in the DEB-TACE group was much greater than that in the cTACE group [relative risk (RR) = 1.42, 95%CI: 1.18–1.72, P = 0.0002]. The 12-month survival rate significantly increased (RR = 1.09; 95%CI: 1.01- 1.17, P = 0.03); the PR rate (RR = 1.13; 95%CI: 0.97-1.30, P = 0.12); the SD rate (RR = 0.82; 95%CI: 0.64-1.05, P = 0.12); and the 6-month survival rate (RR = 1.05; 95%CI: 1.00-1.10, P = 0.07). There was no significant difference (P < 0.05). CONCLUSION Compared with those of iodized oil TACE, the drug-loaded microspheres tended to have therapeutic advantages.

A Pioneer Review on Lactoferrin-Conjugated Extracellular Nanovesicles for Targeting Cellular Melanoma: Recent Advancements and Future Prospects.

Melanoma, a highly aggressive form of skin cancer, presents a formidable challenge in terms of treatment due to its propensity for metastasis and resistance to conventional therapies. The development of innovative nanocarriers for targeted drug delivery has opened new avenues in cancer therapy. Lactoferrin-conjugated extracellular nanovesicles (LF-EVs) have emerged as a promising vehicle in the targeted treatment of cellular melanoma, owing to their natural biocompatibility, enhanced bioavailability, and ability to traverse biological barriers effectively. This review synthesizes recent advancements in the use of LF-EVs as a novel drug delivery system for melanoma, emphasizing their unique capacity to enhance cellular uptake through LF's receptor-mediated endocytosis pathways. Key studies demonstrate that LF conjugation significantly increases the specificity of extracellular nanovesicles for melanoma cells, minimizes off-target effects, and promotes efficient intracellular drug release. Furthermore, we explore how LF-EVs interact with the tumor microenvironment, potentially inhibiting melanoma progression and metastasis while supporting antitumor immune responses. Future prospects in this field include optimizing LF conjugation techniques, improving the scalability of LF-EV production, and integrating multifunctional payloads to target drug resistance mechanisms. This review highlights the potential of LF-EVs to transform melanoma treatment strategies, bridging current gaps in therapeutic delivery and paving the way for personalized and less invasive melanoma therapies.

Amphiphilic self-assembling peptides: formulation and elucidation of functional nanostructures for imaging and smart drug delivery.

The rational design of self-assembled peptide-based nanostructures for theranostics applications requires in-depth physicochemical characterization of the peptide nanostructures, to understand the mechanism and the interactions involved in the self-assembly, allowing a better control of the objects' physicochemical and functional properties for theranostic applications. In this work, several complementary characterization methods, such as dynamic light scattering, transmission electron microscopy, circular dichroism, Taylor dispersion analysis, and capillary electrophoresis, were used to study and optimize the self-assembly of pH-sensitive short synthetic amphiphilic peptides containing an RGD motif for active targeting of tumor cells and smart drug delivery. The combined methods evidenced the spontaneous formation of nanorods (L = 50nm, d = 10nm) at pH 11, stabilized by β-sheets. To complement with imaging properties for diagnosis, a new strategy was developed by designing an optimized peptide sequence to allow for efficient functionalization with a contrast agent, while preserving the self-assembling properties. Co-assemblies of the peptide and its derivatives, after peptide modification with a gadolinium complex, exhibited similar nanorod structures and required properties for drug delivery and imaging applications in vivo.

Design and comparison of the drug delivery systems of pegylated doxorubicin loaded Zn-CP and Zn-CP-SO3H

Design and comparison of the drug delivery systems of pegylated doxorubicin loaded Zn-CP and Zn-CP-SO3H

A Review on the Effects of Caffeine on Human Health

Caffeine is the world’s most popular stimulant and psychoactive substance. Given the universal use of caffeine, it is crucial for us to comprehend how our body interacts with caffeine. The pharmacokinetics of caffeine and its action mechanisms have been reviewed in this paper. The safety and recommended dosage of caffeine in healthy adults and vulnerable populations like children and pregnant women are also discussed in this paper. While caffeine consumption is generally safe, this review paper also examines the potential effects that caffeine could have on human health and development. Studies indicated that caffeine exhibits neuroprotective properties, potentially serving as a preventive measure against the onset of neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. The article also explores various physiological effects of caffeine on the body, in addition to investigating novel drug delivery techniques, particularly nano-delivery systems designed to efficiently administer caffeine

Advances in dorzolamide hydrochloride delivery: harnessing nanotechnology for enhanced ocular drug delivery in glaucoma management.

Dorzolamide hydrochloride (DRZ) is a carbonic anhydrase inhibitor utilized in managing elevated intraocular pressure (IOP) associated with glaucoma. However, its clinical effectiveness is hindered by a short half-life, low residence time, and the need for frequent dosing, highlighting the necessity for innovative delivery systems. This work reviews recent advancements in DRZ delivery, particularly focusing on cyclodextrin complexation and nanotechnology applications. It explores the potential of cyclodextrin derivatives to enhance DRZ's bioavailability. DRZ cyclodextrin complexes or nanoparticulate systems maintain high drug concentrations in the eye while minimizing irritation and viscosity-related issues. Nanotechnology introduces nanoparticle-based carriers such as polymeric nanoparticles, solid lipid nanoparticles, liposomes, niosomes, and nanoemulsions. These formulations enable sustained drug release, improved corneal permeation, and enhanced patient compliance. Clinical trials have shown that DRZ nanoparticle eye drops and nanoliposome formulations offer efficacy comparable to conventional therapies, with the potential for better tolerability. Overall, this review highlights significant progress in DRZ delivery systems, suggesting their potential to transform glaucoma treatment by addressing current limitations and improving therapeutic outcomes.

"Carnosine-Niosomal Delivery System for Targeted Cancer Therapy".

Cancer is considered to be among the main causes of death worldwide. Treatment options for cancer are numerous. The type of cancer and its stage of progression determine which kind of treatment is needed. Nanomedicine is a new field for the treatment of various diseases. Pharmaceutical nanocarriers can be fabricated from various materials such as polymers, metals, or lipid-based surfactants. Carnosine-loaded niosomes have emerged as a promising approach in targeted cancer therapy, offering potential advantages over conventional treatments such as chemotherapy and radiation, by improving drug delivery specificity and reducing side effects. The study demonstrates that the encapsulation of carnosine in niosomes enhances its stability and bioavailability, leading to a significant increase in anticancer efficacy. These findings suggest that niosome technology can serve as an effective delivery system for carnosine, potentially transforming its use in cancer treatment and paving the way for future research in targeted therapies. Nanomaterials provide a good delivery system for this method of treatment. It's used in the treatment and diagnosis of diseases. Numerous investigations have been conducted on nanoscale vesicular systems, such as the most recent generations of vesicular nanocarriers, liposomes, and niosomes. Lipophilic and hydrophilic bioactive chemicals are transported via the niosomes in a vesicle. Since niosomes are composed of non-ionic surfactants mixed with cholesterol or other amphiphilic substances, they have a wide range of applications. The therapy of cancer with carnosine-loaded niosomes is one of these uses. The body synthesizes carnosine, a histidine-containing dipeptide, by enzymatically mixing L-histidine and β-alanine. With its antioxidant activities, Carnosine is considered a drug that can reduce and treat cancerous cells and many other therapeutic applications.

In Situ Transformable Nanoparticle Effectively Suppresses Bladder Cancer by Damaging Mitochondria and Blocking Mitochondrial Autophagy Flux.

Tumor therapeutic strategies based on mitochondrial damage have become an emerging trend. However, the low drug delivery efficiency caused by lysosomal sequestration and the activation of protective mitochondrial autophagy severely restricts the therapeutic efficacy. Herein, an in situ transformable nanoparticle named KCKT is developed to promote lysosomal escape and directly damage mitochondria while blocking mitochondrial autophagy. KCKT exhibits acid responsiveness for precise self-assembly into nanofibers within the lysosomes of cancer cells. The massive accumulation of nanofibers and excessive production of reactive oxygen species (ROS) under sonodynamic therapy synergistically induce lysosomal damage. This facilitates the escape of nanofibers from lysosomal sequestration, thereby enhancing drug delivery. Subsequently, the escaped nanofibers specifically aggregate around the mitochondria for long-term retention and generate ROS under ultrasound irradiation to induce mitochondrial damage. Notably, due to lysosomal dysfunction, damaged mitochondria cannot be cleared by autophagy, further aggravating oxidative damage. These results reveal that KCKT effectively improves drug delivery and mitochondria-targeted therapy efficiency by blocking protective autophagy. These findings hold significant potential for advancing the field of mitochondria-targeted therapy.

Recent progress in topical and transdermal approaches for melanoma treatment.

The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma.

Optical clearing with tartrazine enables deep transscleral imaging with optical coherence tomography.

Imaging deep structures with optical coherence tomography (OCT) is difficult in highly scattering biological tissue, such as the sclera. There is a need to visualize the suprachoroidal space and choroid through the sclera to study suprachoroidal drug delivery. We aim to develop optical methods to image through the highly scattering sclera with a custom-built OCT system to visualize the suprachoroidal space and drug delivery within. We developed a custom handheld OCT scanner to image the anterior segment and suprachoroidal space in ex vivo eye models. Tartrazine (Yellow 5) solution, which has been shown to optically clear biological tissue in the visible regime, was tested as a clearing agent to optimize near infrared OCT imaging through the sclera. Tartrazine dramatically increased OCT signal return from the deeper sclera and choroid and thus enabled visualization of the suprachoroidal drug delivery after transscleral injection. We demonstrated successful optical clearing of the thick, porcine sclera with a compact handheld OCT system to image the suprachoroidal space. We believe there is broader potential to use optical clearing with handheld OCT for a variety of previously inaccessible, highly scattering tissue samples.

Unveiling Interactions between Self-Assembling Peptides and Neuronal Membranes.

The use of self-assembling peptide hydrogels in the treatment of spinal cord and brain injuries, especially when combined with adult neural stem cells, has shown great potential. To advance tissue engineering, it is essential to understand the effect of mechanochemical signaling on cellular differentiation. The elucidation of the molecular interactions at the level of the neuronal membrane still represents a promising area of investigation for many drug delivery and tissue engineering applications. An innovative molecular dynamics framework has been introduced to investigate the effect of SAP fibrils with different charges on neural membrane lipid domain dynamics. Such advance enables the in silico exploration of the biomimetic properties of SAP hydrogels and other polymeric biomaterials for tissue engineering applications.

Current Advances in Viral Nanoparticles for Biomedicine.

Viral nanoparticles (VNPs) have emerged as crucial tools in the field of biomedicine. Leveraging their biological and physicochemical properties, VNPs exhibit significant advantages in the prevention, diagnosis, and treatment of human diseases. Through techniques such as chemical bioconjugation, infusion, genetic engineering, and encapsulation, these VNPs have been endowed with multifunctional capabilities, including the display of functional peptides or proteins, encapsulation of therapeutic drugs or inorganic particles, integration with imaging agents, and conjugation with bioactive molecules. This review provides an in-depth analysis of VNPs in biomedicine, elucidating their diverse types, distinctive features, production methods, and complex design principles behind multifunctional VNPs. It highlights recent innovative research and various applications, covering their roles in imaging, drug delivery, therapeutics, gene delivery, vaccines, immunotherapy, and tissue regeneration. Additionally, the review provides an assessment of their safety and biocompatibility and discusses challenges and future opportunities in the field, underscoring the vast potential and evolving nature of VNP research.

Framework Nucleic Acids: Innovative Tools for Cellular Sensing and Therapeutics.

As emerging biomaterials, framework nucleic acids (FNAs) have recently demonstrated great potential in the biomedical field due to their high programmability, biocompatibility, unique structural diversity, and precise molecular design capabilities. This review focuses on the applications of FNAs in cellular sensing and disease treatment. First, we systematically introduce the applications of FNAs in cellular sensing, including their precise recognition and response to the extracellular tumor microenvironment, cell membrane proteins, and intracellular biomarkers. Subsequently, we review the potential of FNAs in disease treatment, covering their applications and development in drug delivery, regulation of cell behavior, and immunomodulation. We also discuss the limitations and potential role of FNAs in personalized medicine, precision diagnostics, and advanced therapies. The broad application of FNAs is expected to drive significant breakthroughs in future biomedical technological innovations and clinical translation.

Tumor-Targeted Magnetic Micelles for Magnetic Resonance Imaging, Drug Delivery, and Overcoming Multidrug Resistance

Tumor-Targeted Magnetic Micelles for Magnetic Resonance Imaging, Drug Delivery, and Overcoming Multidrug Resistance

Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System

Background: CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol)2000 (DSPE-PEG2000) to improve the anti-tumor effect of CY1-4. Methods: The solubility and dissolution of MSNM@CY1-4 were investigated, and its bioavailability, anti-tumor efficacy, IDO inhibitory ability and immune mechanism were evaluated in vivo. Results: CY1-4 was loaded in MSNM@CY1-4 in an amorphous form, and MSNM@CY1-4 could significantly improve the solubility (up to about 200 times) and dissolution rate of CY1-4. In vivo studies showed that the oral bioavailability of CY1-4 in 20 mg/kg MSNM@CY1-4 was about 23.9-fold more than that in 50 mg/kg CY1-4 suspension. In B16F10 tumor-bearing mice, MSNM@CY1-4 significantly inhibited tumor growth, prolonged survival time, significantly inhibited IDO activity in blood and tumor tissues, and reduced Tregs in tumor tissues and tumor-draining lymph nodes to improve anti-tumor efficacy. Conclusions: The nano-skeleton drug delivery system (MSNM@CY1-4) constructed in this study is a potential drug delivery platform for improving the anti-tumor effect of oral poorly water-soluble CY1-4.

Abstract A001: Navigating the future of therapeutic development: innovations in safety and efficacy through advanced research methodologies and nanotechnology

Abstract In recent years, the field of therapeutic development has experienced a significant paradigm shift driven by strategic scientific innovations that prioritize safety and efficacy in therapeutic agents. This paper explores the intersection of advanced research methodologies, novel material sciences, and biotechnological advancements that are revolutionizing the approach to drug formulation and delivery systems. The integration of precision medicine principles alongside cutting-edge technologies allows for the design of therapeutics that are not only effective in targeting specific diseases but are also engineered to minimize adverse effects associated with conventional therapies. One focal point of this exploration is the application of nanotechnology in drug delivery systems. By utilizing nanoparticles, researchers can enhance the bioavailability of therapeutic agents while reducing systemic toxicity. This targeted approach enables the delivery of higher concentrations of drugs to the affected areas, thereby maximizing therapeutic efficacy and minimizing side effects. Additionally, the paper highlights the role of computational modeling and simulations in predicting the interaction of therapeutic agents at the molecular level, facilitating the identification of safer compounds through virtual screening methods. Another significant aspect addressed in this paper is the development of biologics and biosimilars as safer alternatives to traditional synthetic drugs. The advancement of biomanufacturing processes has made it feasible to produce complex molecules with high specificity and reduced immunogenicity, paving the way for innovative therapies that cater to individual patient profiles. Furthermore, the strategic incorporation of pharmacogenomics in drug development allows for the customization of therapeutic agents, ensuring that treatment regimens are tailored to the genetic makeup of patients, which can drastically improve safety and treatment outcomes. The paper also discusses the regulatory landscape surrounding the introduction of these innovative therapeutic agents. It emphasizes the need for adaptive regulatory frameworks that keep pace with scientific advancements while ensuring patient safety and efficacy. Collaborative efforts between researchers, regulatory bodies, and pharmaceutical companies are essential to facilitate the translation of innovative therapies from the laboratory to clinical practice. In conclusion, this paper underscores the critical importance of strategic scientific innovations in the quest for safer therapeutic agents. By harnessing the potential of advanced technologies, researchers can develop therapeutics that not only meet the growing demand for efficacy but also uphold the highest standards of safety, ultimately improving patient care and health outcomes. The findings presented advocate for continued investment in research and collaboration across disciplines to drive future advancements in therapeutic development. Citation Format: Peter O. David. Navigating the future of therapeutic development: innovations in safety and efficacy through advanced research methodologies and nanotechnology. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A001

Nanotechnology-Based Approaches for the Management of Diabetes Mellitus: An Innovative Solution to Long-Lasting Challenges in Antidiabetic Drug Delivery

Diabetes is a widespread metabolic illness. Mismanagement of diabetes can lead to severe complications that tremendously impact patients’ quality of life. The assimilation of nanotechnology in diabetes care holds the potential to revolutionize treatment paradigms, improve patient outcomes, and reduce the economic burden associated with this pervasive disease. This manuscript explores the multifaceted utilization of nanomaterials in diabetes care, emphasizing the unique features of nano-based medication delivery methods and smart drug delivery mechanisms. Additionally, this paper talks about research on nanocarrier-integrated oral, transdermal, and inhalable insulin delivery; dendrimer- and nanocarrier-coupled antisense oligonucleotide-driven gene therapy; the implementation of gold nanoparticles and quantum dots for glucose surveillance; and nucleic acid therapies. There are certain restrictions when using medication delivery methods that are commonly available to handle diabetes. In order to increase efficacy and safety, the rapidly developing science of nanotechnology is also being explored and employed in medical biology. Nanomaterials like liposomes, dendrimers, niosomes, polymeric and metallic nanocarriers, and solid lipid nanoparticles are among the nanocarriers that have been developed for better delivery of various oral hypoglycemic agents in comparison to conventional therapies. These nanocarriers provide great control over elevated blood glucose levels, making them one of the most intriguing and promising technologies available today. Furthermore, adding additional ligands to nanocarriers allows for more focused distribution while protecting the encapsulated hypoglycemic drugs.

Supramolecular Organic Framework that Enables Multifunctional Doxorubicin Delivery, Photofrin Post-treatment Phototoxicity Inhibition, and Heparin Neutralization.

Although porous frameworks are structurally ideal for the development of biomaterials through drug adsorption, sequestration, and delivery, integration of multiple biofunctions into a biocompatible porous framework would greatly improve its potential for preclinical investigations by increasing both therapeutic value and research and development efficiency. Herein, we report the preparation of a highly biocompatible supramolecular organic framework from an imidazolium-derived tetrahedral monomer and cucurbit[8]uril. The supramolecular organic framework has been revealed to have regular intrinsic porosity and adsorb doxorubicin, photofrin, and heparins driven by hydrophobicity and/or ion-pairing electrostatic interactions. In vivo or in vitro assays illustrate that this adsorption leads to efficient intracellular delivery of doxorubicin, which enhances its antitumor efficacy, elimination of photofrin, which inhibits its post-treatment phototoxicity without reducing its photodynamic therapeutic activity, and sequestration of (low-molecular-weight) heparins, which neutralizes their anticoagulation activity more efficiently than clinically used protamine.

Abstract IA011: Strategies to close the translational gap for nanoscale drug delivery systems

Abstract Nanoscale drug delivery systems have enormous potential to leverage innovative chemistry and encapsulate a wide range of cargo. However, compared to the large number and diverse scope of nanoscale systems described in preclinical manuscripts, there are relatively few approved drug products representing a narrow range of chemistries. There are many reasons for this translational gap, ranging from manufacturing and regulatory challenges to clinical relevance and safety. This presentation outlines key strategies to address the multifaceted challenges that hinder the clinical adoption of nanoscale drug delivery systems. One of the first barriers is the difficulty of scaling up the production of nanoscale systems while maintaining quality and consistency. An illustrative case study will be shared of an approved nanotherapeutic becoming unavailable due to manufacturing concerns, and the resultant change in clinical practice. For a new investigational agent, the work required to optimize a promising nanoformulation is time-consuming and may not result in immediate, publishable findings, creating tension between essential translational work and projects more likely to yield high-profile publications and contribute to academic promotion. In the industry setting, successfully navigating this hurdle is likely to require significant capital, again without a guarantee of success. Without a stable and robust formulation that can be scaled for good manufacturing practice, the benefits of an innovative formulation cannot be fully realized. Another key principle underlying successful translation is identifying a clear clinical indication, which will guide clinical trial design and improve the likelihood of regulatory approval. Recent data suggest that national research funding trends heavily influence the focus of nanotechnology studies, resulting in a misalignment between clinical needs and the investigational agents being developed. In the future, a funding re-alignment may open additional opportunities for basket trials in patient populations lacking a standard of care, or in diseases where the current treatment options are highly toxic. Expanding the clinical indications for nanotherapeutics will likely require academic-industry partnerships to bring together a robust drug product and a strong clinical rationale. The regulatory process for nanoscale therapeutics is evolving, making early communication between investigators and regulators crucial for successfully transitioning nanoscale drug delivery systems from the lab to clinical use for cancer patients. Citation Format: Joelle P. Straehla. Strategies to close the translational gap for nanoscale drug delivery systems [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA011.