Delivery Of Therapeutic Agents Research Articles

A targeting multiple-stimuli responsive POSS-based smart nanomaterial for enhanced chemo-photothermal synergistic therapy

The combination of chemotherapy and photothermal therapy has garnered significant attention in the field of multimodal cancer therapy. However, achieving precise and controllable delivery of therapeutic agents remains a challenge. In this study, we designed a biocompatible smart nanomaterial (PSD-FA) for efficient loading of doxorubicin (DOX) through dynamic chemical bonding, with the aim of achieving responsive behavior to both the tumor microenvironment (TME) and external laser irradiation. The incorporation of PEG into the nanoplatform enhanced hydrophilicity of PSD-FA NPs. Folic acid (FA) served as a targeting ligand to guide the nanoparticles tumor sites. On one hand, SQ-N acted as an effective photothermal agent that efficiently converted light energy into heat energy upon stimulation by exogenous near-infrared light. This localized increase in temperature at the tumor site facilitated targeted killing of tumor cells. On the other hand, after photothermal therapy-induced tumor ablation, DOX was released in response to redox stimuli due to significantly higher concentrations of glutathione (GSH), an antioxidant presents in TME. This allowed deep penetration into the tumor tissue, expanding the attack area and inhibiting nucleic acid synthesis in tumor cells, ultimately leading to cell death. Both in vitro and in vivo experiments demonstrated excellent anticancer efficacy of PSD-FA NPs. Overall, this intelligent nanomaterial successfully achieved targeted drug delivery with redox-responsive release capabilities while synergistically combining chemo-photothermal therapies, thus exhibiting great potential for clinical applications.

High-Affinity NIR-Fluorescent Inhibitors for Tumor Imaging via Carbonic Anhydrase IX.

Tumor imaging and delivery of therapeutic agents may be achieved by designing high-affinity and high-selectivity compounds recognizing a tumor cell-expressing biomarker, such as carbonic anhydrase IX (CA IX). The CAIX, overexpressed in many hypoxic solid tumors, helps adjust to the energy requirements of the hypoxic environment, reduces intracellular acidification, and participates in the metastatic invasion of adjacent tissues. Here, we designed a series of sulfonamide compounds bearing CAIX-recognizing, high-affinity, and high-selectivity groups conjugated via a PEG linker to near-infrared (NIR) fluorescent probes used in the clinic for optically guided cancer surgery. We determined compound affinities for CAIX and other 11 catalytically active CA isozymes by the thermal shift assay and showed that the affinity Kd value of CAIX was in the subnanomolar range, hundred to thousand-fold higher than those of other CA isozymes. Similar affinities were also observed for CAIX expressed on the cancer cell surface in live HeLa cell cultures, as determined by the competition assay. The NIR-fluorescent compounds showed excellent properties in visualizing CAIX-positive tumors but not CAIX-negative knockout tumors in a nude mice xenograft model. These compounds would therefore be helpful in optically guided cancer surgery and could potentially be developed for anticancer treatment by radiotherapy.

Advancing Transdermal Delivery by Zn/Ag-Electrode-Printed Iontophoretic Patch with Self-Generating Microcurrents

This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed patches increased the transdermal depth of fluorescein into the dermis, while the permeation of fluorescein was limited when Zn/C-electrode-printed patches were tested. Further permeation experiments were conducted with 3D skin models, which showed a similar trend to the above, indicating that Zn/Ag-electrode-printed patches had a higher penetration rate compared to the blank. Studies using acetyl hexapeptide-8 as a peptide drug model and sodium ascorbyl phosphate (SAP) as a hydrophilic derivative of ascorbic acid showed that the iontophoretic patch with Zn/Ag electrodes promoted more penetration of drugs than unprinted patches. The permeation of SAP exhibited a two-phase profile with a relatively rapid permeation followed by a sustained, slower permeation. The permeation of acetyl hexapeptide-8 was slower due to its higher molecular weight, but the iontophoretic patch increased the permeation up to 1.5 times more than the unprinted patch. The microcurrent generated by the patch drives the transport of small molecule components through the skin, for the controlled and efficient delivery of therapeutic agents. The flexible design, efficient microcurrent generation, and stable electrodes make the Zn/Ag-electrode-printed patch a promising tool for transdermal drug delivery.

Cascade Nanoreactor Employs Mitochondrial-Directed Chemodynamic and δ-ALA-Mediated Photodynamic Synergy for Deep-Seated Oral Cancer Therapy.

The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. A cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment is introduced. Utilizing iron oxide and mesoporous silica, the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA), is developed. Triphenylphosphine (TPP) modification facilitates mitochondrial targeting, while tumor cell membrane (TCM) coating provides homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM demonstrate efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggers δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria undergoes Fenton chemistry for CDT. The synergistic interaction of PDT and CDT increases cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic mechanisms, ultimately leading to tumor cell death. PDT/CDT-induced apoptosis generates δ-ALA-containing apoptotic bodies, enhancing antitumor efficacy in deep tumor cells. The anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment.

Recent advances in cell membrane camouflaged nanotherapeutics for the treatment of bacterial infection.

Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.&#xD.

Autonomous Needle Navigation in Subretinal Injections via iOCT.

Subretinal injection is an effective method for direct delivery of therapeutic agents to treat prevalent subretinal diseases. Among the challenges for surgeons are physiological hand tremor, difficulty resolving single-micron scale depth perception, and lack of tactile feedback. The recent introduction of intraoperative Optical Coherence Tomography (iOCT) enables precise depth information during subretinal surgery. However, even when relying on iOCT, achieving the required micron-scale precision remains a significant surgical challenge. This work presents a robot-assisted workflow for high-precision autonomous needle navigation for subretinal injection. The workflow includes online registration between robot and iOCT coordinates; tool-tip localization in iOCT coordinates using a Convolutional Neural Network (CNN); and tool-tip planning and tracking system using real-time Model Predictive Control (MPC). The proposed workflow is validated using a silicone eye phantom and ex vivo porcine eyes. The experimental results demonstrate that the mean error to reach the user-defined target and the mean procedure duration are within an acceptable precision range. The proposed workflow achieves a 100% success rate for subretinal injection, while maintaining scleral forces at the scleral insertion point below 15mN throughout the navigation procedures.

Structural and molecular basis of choline uptake into the brain by FLVCR2.

Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain remains unknown1-3. The major facilitator superfamily transporter FLVCR1 (also known as MFSD7B or SLC49A1) was recently determined to be a choline transporter but is not highly expressed at the blood-brain barrier, whereas the related protein FLVCR2 (also known as MFSD7C or SLC49A2) is expressed in endothelial cells at the blood-brain barrier4-7. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus and embryonic lethality, but the physiological role of FLVCR2 is unknown4,5. Here we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in both inward-facing and outward-facing states using cryo-electron microscopy. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of therapeutic agents into the brain.

Incorporation of immunotherapies and nanomedicine to better normalize angiogenesis-based cancer treatment.

Neoadjuvant targeting of tumor angiogenesis has been developed and approved for the treatment of malignant tumors. However, vascular disruption leads to tumor hypoxia, which exacerbates the treatment process and causes drug resistance. In addition, successful delivery of therapeutic agents and efficacy of radiotherapy require normal vascular networks and sufficient oxygen, which complete tumor vasculopathy hinders their efficacy. In view of this controversy, an optimal dose of FDA-approved anti-angiogenic agents and combination with other therapies, such as immunotherapy and the use of nanocarrier-mediated targeted therapy, could improve therapeutic regimens, reduce the need for administration of high doses of chemotherapeutic agents and subsequently reduce side effects. Here, we review the mechanism of anti-angiogenic agents, highlight the challenges of existing therapies, and present how the combination of immunotherapies and nanomedicine could improve angiogenesis-based tumor treatment.

Targeted therapy of gastric cancer with gingerol-loaded hyaluronic acid/PEG-coated PLGA nanoparticles: Development and physicochemical evaluation

In recent years, nanoparticle (NP)-based drug delivery systems have emerged as promising candidates for targeted therapy due to their ability to enhance drug bioavailability and delivery of therapeutic agents to tumor sites. Herein, we aim to develop gingerol-hyaluronic acid (HA)-poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-NPs (gingerol-HA-NPs) as a targeted therapy for gastric cancer. To target the CD44 receptor expressed on malignant cells, gingerol-HA-NPs were fabricated using a single-emulsion solvent evaporation method. The physicochemical properties and cytotoxicity of the NPs were characterized, and their cellular uptake was assessed using flow cytometry analysis. Flow cytometry analysis of FITC-labeled annexin V/PI-stained cells was used to evaluate the induction of apoptosis/necrosis by the NPs. In vitro release studies demonstrated sustained and controlled release of gingerol from the NPs over 72 h. The release kinetics followed the Peppas-Korsmeyer model, suggesting that drug release was influenced by polymer erosion and disentanglement. Also, the NPs showed dose-dependent cytotoxic effects on MKN cells, with lower IC50 values than plain gingerol. The IC50 values for gingerol-PLGA-PEG-NPs (gingerol-NPs) and gingerol-HA-NPs were 175 μM and 117 μM, respectively after 48 h, while the IC50 value for plain gingerol was 202 μM. Gingerol-HA-NPs exhibited higher cellular uptake in MKN cells (CD44+) compared to plain drug and gingerol-NPs. The uptake increased with prolonged incubation. The analysis of apoptosis/necrosis detection showed that the gingerol-HA-NPs caused a greater occurrence of late apoptosis (An+/PI+) in MKN cells compared to plain gingerol and gingerol-NPs, with percentages of 76.43 %, 11.58 %, and 24.03 % respectively. These results underscore the potential of gingerol-HA-NPs as a promising targeted therapy for the treatment of gastric cancer.

In silico modeling, development, characterization, in-vitro cytotoxicity, pharmacokinetic, and toxicological studies of folate-receptor targeted micelles containing cisplatin and upconversion nanoparticles for lung cancer therapy

Folate receptor α (FRα) is one of the best motifs to recognize lung cancer, therefore it can be utilized for targeted delivery of therapeutic agents in lung cancer therapy. Herein, we developed folate-receptor-targeted micelles (CPTT-FA) for the co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) as theranostics for lung cancer therapy. Initially, the binding affinity of FRα (4MK6) was studied, resulting in good docking scores of −7.6 towards 4MK6 by stimulating PI3K inhibition in lung cancer cells. Micelles, fabricated using the solvent-casting technique, exhibited favorable characteristics, including an average size ranging from 80 to 190 nm with a narrow size distribution and spherical morphology. The zeta potential of −29.4 mV indicates stability and potential for targeted delivery. The drug encapsulation efficiency of the micelles was high, ranging from 70 % to 90 %. In vitro, release studies demonstrated an initial burst release of 40 % within 4 h, the release rate was controlled up to 72 h in PBS at pH 6.8. Afterthat, IC50 of the CPTT-FA micelles was found to be 11.6-fold lower than Ciszest-50. Heamolysis study has proven the greater biocompatibility of CPTT-FA. Pharmacokinetic investigations exhibited a significant enhancement with a three-fold increase in the area under the concentration-time curve (AUC0-t) and a 3.7-fold extension in half-life (t1/2). CDDP resistance in lung cancer presents a promising avenue for targeted therapy using UCNP, addressing challenges posed by FRα-positive cases and improving prognosis. Further clinical investigations are needed to validate the effectiveness and safety of this approach before its widespread implementation.

Mesenchymal stem cells as therapeutic vehicles for glioma.

Glioma is a disease with a poor prognosis despite the availability of multimodality treatments, and the development of novel therapies is urgently needed. Challenges in glioma treatment include the difficulty for drugs to cross the blood-brain barrier when administered systemically and poor drug diffusion when administered locally. Mesenchymal stem cells exhibit advantages for glioma therapy because of their ability to pass through the blood-brain barrier and migrate to tumor cells and their tolerance to the immune system. Therefore, mesenchymal stem cells have been explored as vehicles for various therapeutic agents for glioma treatment. Mesenchymal stem cells loaded with chemotherapeutic drugs show improved penetration and tumor accumulation. For gene therapy, mesenchymal stem cells can be used as vehicles for suicide genes, the so-called gene-directed enzyme prodrug therapy. Mesenchymal stem cell-based oncolytic viral therapies have been attempted in recent years to enhance the efficacy of infection against the tumor, viral replication, and distribution of viral particles. Many uncertainties remain regarding the function and behavior of mesenchymal stem cells in gliomas. However, strategies to increase mesenchymal stem cell migration to gliomas may improve the delivery of therapeutic agents and enhance their anti-tumor effects, representing promising potential for patient treatment.

Optimizing Wound Healing: Examining the Influence of Biopolymers Through a Comprehensive Review of Nanohydrogel-Embedded Nanoparticles in Advancing Regenerative Medicine.

Nanohydrogel wound healing refers to the use of nanotechnology-based hydrogel materials to promote the healing of wounds. Hydrogel dressings are made up of a three-dimensional network of hydrophilic polymers that can absorb and retain large amounts of water or other fluids. Nanohydrogels take this concept further by incorporating nanoscale particles or structures into the hydrogel matrix. These nanoparticles can be made of various materials, such as silver, zinc oxide, or nanoparticles derived from natural substances like chitosan. The inclusion of nanoparticles can provide additional properties and benefits to the hydrogel dressings. Nanohydrogels can be designed to release bioactive substances, such as growth factors or drugs, in a controlled manner. This allows for targeted delivery of therapeutics to the wound site, promoting healing and reducing inflammation. Nanoparticles can reinforce the structure of hydrogels, improving their mechanical strength and stability. Nanohydrogels often incorporate antimicrobial nanoparticles, such as silver or zinc oxide. These nanoparticles have shown effective antimicrobial activity against a wide range of bacteria, fungi, and other pathogens. By incorporating them into hydrogel dressings, nanohydrogels can help prevent or reduce the risk of infection in wounds. Nanohydrogels can be designed to encapsulate and release bioactive substances, such as growth factors, peptides, or drugs, in a controlled and sustained manner. This targeted delivery of therapeutic agents promotes wound healing by facilitating cell proliferation, reducing inflammation, and supporting tissue regeneration. The unique properties of nanohydrogels, including their ability to maintain a moist environment and deliver bioactive agents, can help accelerate the wound healing process. By creating an optimal environment for cell growth and tissue repair, nanohydrogels can promote faster and more efficient healing of wounds.

Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium–indium LM particles were first stabilized with 1,2-Distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. Statement of significanceOur research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

SmartLipids: Ushering in a New Era of Lipid Nanoparticles for Drug Delivery

Abstract: In the realm of drug delivery, lipid nanoparticles have emerged as versatile carriers, offering enhanced encapsulation, protection, and targeted delivery of therapeutic agents. Among these innovative systems, SmartLipids stands out as a groundbreaking advancement, representing the latest generation of lipid nanoparticles. Characterized by their unique "chaotic" and disordered particle matrix structure, SmartLipids exhibit remarkable properties that set them apart from conventional drug delivery systems. This comprehensive review delves into the intricate world of SmartLipids, unraveling their distinctive features and exploring their immense potential in the field of drug delivery. It meticulously outlines their production methods, shedding light on the solvent-free, highpressure homogenization technique that ensures biocompatibility and safety. The review meticulously examines the physicochemical characterization of SmartLipids, providing insights into their particle size, morphology, and encapsulation efficiency. It further delves into their in vitro and in vivo performance, highlighting their ability to enhance drug solubility, permeability, and bioavailability. The study collectively underscores the versatility and customizable nature of SmartLipids, emphasizing their suitability for a wide range of drug delivery applications. From encapsulating hydrophilic, lipophilic, and amphiphilic compounds to tailoring specific release profiles, SmartLipids offer a remarkable degree of flexibility in drug delivery strategies.

Dentifrices. Part 3: Dentifrice Recommendations

This article, the third in a series about dentifrices, emphasizes the essential role of dentifrices in oral healthcare, highlighting their contributions beyond mechanical plaque removal to include plaque inhibition and delivery of therapeutic agents. Despite the sometimes-limited impact on mechanical plaque removal, the importance of fluoridated dentifrices, must not be underestimated. The article reviews the effectiveness and safety of dentifrices, including the challenges posed by subjective clinical indices and potential allergenic ingredients. It discusses the potential of innovative dentifrice formulations to improve compliance and oral health outcomes. Additionally, it emphasizes the critical role of dental care professionals in recommending dentifrices based on safety and effectiveness rather than cosmetic claims or cost. Through an analysis of the literature and clinical guidelines, this work aims to guide healthcare providers in making informed decisions about dentifrice recommendations for optimal oral health. CPD/Clinical Relevance: Dentifrices are complex formulations that need to be proven effective in (clinical) trials and be appreciated by end users.

Current approaches in smart nano-inspired drug delivery: A narrative review.

The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side-effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off-target side-effects. A literature search was done to collate papers and reports about the currently available various strategies for smart nano-inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Smart drug delivery is a cutting-edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side-effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine.

Evaluation of Antidiabetic Activity and Cytotoxic Effect of Strontium Nanoparticles Synthesized Using Mimosa Pudica

ABSTRACT Nanotechnology is emerging as a promising approach in the development of novel therapeutic strategies. Nanoparticles, due to their unique physicochemical properties and small size, have the potential to improve the delivery of therapeutic agents, enhance their bioavailability, and increase their efficacy. Among various types of nanoparticles, strontium nanoparticles have gained attention due to their potential antidiabetic activity and cytotoxic effects against cancer cells. Mimosa pudica, also known as “Sensitive Plant” or “Touch-Me-Not,” is a medicinal plant known for its diverse pharmacological activities, including antidiabetic and anticancer properties. Recent research has focused on the synthesis of strontium nanoparticles by using Mimosa pudica as a green and sustainable approach. These nanoparticles have shown promising results in terms of their antidiabetic activity and cytotoxic effects against cancer cells. Thus, in this study, the antidiabetic effect was studied using the alpha-amylase inhibitor assay, and the cytotoxic effect was studied using the brine shrimp lethality assay. In these assays, increasing concentration of Mimosa pudica-mediated strontium nanoparticles exhibited increasing antidiabetic and cytotoxic effects, which was similar to the standard used, which is acarbose. Hence, this can be used as a novel antidiabetic and cytotoxic agent in the future.

495 Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting

INTRODUCTION: Brain metastases are difficult to treat due to the blood-brain barrier limiting delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intra-axial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma. METHODS: We used an intracerebral breast cancer tumor model in adult female nude rats divided into six experimental groups. We examined three iron labeled dextran molecules (3 KD, 5KD, and 10 KD) in 337 mOsm/L solution and three different osmolarities of delivery solution (307, 353, 368 mOsm/L) with 10 KD dextran. 7T MR imaging was used to analyze dextran distribution at different time points. All animals were sacrificed after 2 hours and quantity of dextran particles was determined by histopathology. RESULTS: Breast cancer tumor cells were successfully implanted in all rats. MRI quantification of dextran concentration was well corroborated by histopathology. Varying the molecular size of dextran resulted in the smallest molecule reaching peak levels in tumor tissue earlier than the larger molecules but the larger molecules remained concentrated in tumor tissue for a longer time. Varying the osmolarity of the delivery solution resulted in preferential accumulation of 10 KD dextran in tumor tissue except for when dextran was delivered in 368 mOsm/L solution where no preferential distribution was seen. CONCLUSIONS: Hyperosmolar intraventricular delivery of chemotherapeutic drugs could be effective in preferentially delivering drugs to abnormal tumor tissues.

Current Advances of Nanomaterial-Based Oral Drug Delivery for Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.