Nanocarriers For Drug Delivery Research Articles

Dynamic reorganization of multivesicular bodies and exosome production impacted by sonoporation

Naturally occurring cell-derived extracellular vesicles (EVs) have emerged as attractive nanocarriers for drug delivery. However, production of large quantities of EVs for clinical applications in a scalable manner remains a significant challenge. This study investigated at the single cell level how sonoporation, or membrane poration produced by ultrasound-induced microbubble cavitation, impacts EV production using mouse macrophage RAW 264.7 cells stably expressing CD63-GFP as a model system. Real-time fluorescence videomicroscopy detected rapid changes in CD63-GFP, a tetraspanin family member highly enriched in intraluminal vesicles tagged with GFP, to track changes in multivesicular bodies (MVBs), which are the cellular compartments where exosomes originate within the cells. Our results revealed distinct dynamic changes in CD63-GFP intensity and distribution in RAW 264.7 cells in terms of response time and duration depending on whether the cells were directly or indirectly impacted by sonoporation, suggesting reorganization of MVBs in response to direct and indirect mechanisms resulted from the mechanical impact of ultrasound pulse on the cells. Analysis of the supernatant from sonoporation-treated RAW 264.7 cells expressing CD63-GFP demonstrated a delayed and sustained increase in the production of CD63-GFP-positive EVs. These results show the robust and detailed effect of sonoporation and reveal insights into sonoporation-induced EV release useful for guiding the application of sonoporation to enhance large-scale EV production.

Poloxamer®s anchored with TAT enhance blood–brain barrier penetration of carbamazepine for the treatment of epilepsy: an in vivo study

Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier.Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed.The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity.Graphical

Polymersomes as Next Generation Nanocarriers for Drug Delivery: Recent Advances, Patents, Synthesis and Characterization

Background: Polymersomes (PS), self-assembled nanostructures formed by amphiphilic block copolymers, have garnered significant attention in recent years due to their unique properties and versatile applications in the fields of drug delivery and biomedicine. They are being prepared for a wide range of complex medicinal compounds, including nucleic acids, proteins, and enzymes. Polymersomes have lately been used as vehicles for delivering varied therapeutic substances and regulating ROS (reactive oxygen species). Due to their immunogenic features, polymersomes could play a critical role in enhancing subunit vaccine and drug delivery against COVID-19 infection. Objective: The prime purpose of this manuscript is to furnish an extensive overview of polymersomes, highlighting their recent advances, fabrication methods, characterization techniques, and pharmaceutical applications. Methods: The article has been amassed using several online and offline manuscripts from reputed journals, books, and other resources. Besides this, various user-friendly interfaces, like Pubmed, Google Scholar, etc, have been utilized to gather the latest data about polymersomes. This domain encompasses recent advancements in the realm of innovations about the delivery of drugs through polymeric vesicles. This field involves innovations or developments in nanocarrier systems as they are efficaciously employed to deliver the desired moiety to the targeted site. Results: PS have been discovered to exhibit remarkable promise in addressing various challenges associated with inadequate bioavailability, targeted drug delivery, dosing frequency, and diminished toxic effects. Over the past decade, such nanovesicles have been effectively employed as a complementary approach to address the issues arising from poorly soluble medications. However, this domain still requires further focus on novel breakthroughs. Conclusion: Polymersomes demonstrate unparalleled potential as innovative carriers, exhibiting remarkable versatility and exceptional biocompatibility. This concise review underscores their extraordinary prospects in diverse fields, accentuating their distinctive attributes and opening new avenues for groundbreaking applications.

Safety of Zein Nanoparticles on Human Innate Immunity and Inflammation.

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Plasmomagnetic hybrid gold nanostructures as multifunctional nanocarriers for drug delivery, MRI contrast, and photothermal therapy of drug-resistant cancer cells

Presenting a simple efficient method, plasmomagnetic hybrid nanostructures (PNIPAM coated gold nanorods-dexpion hybrid nanostructure, PN-GDHNs) capable of serving as dual drug nanocarriers, MRI contrast, and photothermal agents for cancer therapy were synthesized. The cisplatin (CDDP) and doxorubicin (DOX) were loaded on PN-GDHNs and tested for their drug release, cytotoxicity, photothermal, and MRI contrast in vitro. We found that the drug release was controlled by pH and temperature, and the cytotoxicity was enhanced by the combination of chemotherapy and photothermal therapy. We also found that the PN-GDHNs could overcome the drug resistance of MCF7 breast cancer cells and improve the MRI contrast. We achieved a high cancer cell-killing efficiency of 97.3 ± 0.4 % in one dose with low drug concentration and laser power. Our results suggest that PN-GDHNs are promising multifunctional nanocarriers for cancer therapy applications.

Stable Porous Organic Cage Nanocapsules for pH-Responsive Anticancer Drug Delivery for Precise Tumor Therapy.

The search for drug nanocarriers with stimuli-responsive properties and high payloads for targeted drug delivery and precision medicine is currently a focal point of biomedical research, but this endeavor still encounters various challenges. Herein, a porous organic cage (POC) is applied to paclitaxel (PTX) drug delivery for cancer therapy for the first time. Specifically, water-soluble, stable, and biocompatible POC-based nanocapsules (PTX@POC@RH40) with PTX encapsulation efficiency over 98% can be synthesized by simply grafting nonionic surfactant (Polyoxyl 40 hydrogenated castor oil, RH40) on the POC surface. These PTX@POC@RH40 nanocapsules demonstrate remarkable stability for more than a week without aggregation and exhibit pH-responsive behavior under acidic conditions (pH 5.5) and display sustained release behavior at both pH 7.4 and pH 5.5. Intravenous administration of PTX@POC@RH40 led to a 3.5-fold increase in PTX bioavailability compared with the free PTX group in rats. Moreover, in vivo mouse model experiments involving 4T1 subcutaneous breast cancer tumors revealed that PTX@POC@RH40 exhibited enhanced anticancer efficacy with minimal toxicity compared with free PTX. These findings underscore the potential of POCs as promising nanocarriers for stimuli-responsive drug delivery in therapeutic applications.

Nanomaterials Marvels: Transformative Advancements in Biomedicine, Drug Delivery, and Pharmaceutical Analysis

Nanoparticles are solid colloidal particles ranging in size from 10 to 1000 nm having high surface area-to-volume ratio which allows them for efficient interaction with biological systems. Nanoparticles offer many benefits in comparison to larger particles such as increased surface-to-volume ratio and increased magnetic properties. Nanomaterials hold the potential to revolutionize in critical domains like Biomedicine, Drug Delivery, and Pharmaceutical Analysis. These particles can be functionalized with specific molecules to target diseased cells or tissues, enhancing the efficacy of drugs while minimizing side effects. For instance, gold nanoparticles conjugated with antibodies can be used for targeted cancer therapy, delivering therapeutic agents directly to tumor cells. Similarly drugs encapsulated within nanoparticles can be protected from premature degradation and released in a controlled manner at the target site improving their drug solubility, and enhance cellular uptake, leading to better therapeutic effect in treatment strategies. Polymeric nanoparticles, liposomes, and micelles are some examples of commonly used nanocarriers for drug delivery. Nanomaterials are finding increasing applications in pharmaceutical analysis and can be employed as highly sensitive detection probes for drugs, metabolites, and biomarkers. Additionally, nanomaterials can be used for the separation and purification of bio molecules, facilitating accurate and efficient analysis. This review explores different types of nano materials used exploring their new advances and applications in biomedicine, drug delivery, and pharmaceutical analysis. As research continues to overcome current challenges, nanomaterials unique properties hold immense promise for revolutionizing healthcare and improving patient outcomes.

Liposome-Assisted Drug Delivery in the Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the nervous system that leads to neurological dysfunctions and severe disabilities. It is worth noting that conventional pharmacotherapy is poorly selective and causes toxicity problems and several systemic side effects. Thus, there is a need to develop new approaches to this medical challenge. The use of nanocarriers for drug delivery represents a good strategy to overcome several issues such as high therapeutic drug doses with side effects, such as diarrhea, nausea, and abdominal pain, and drug degradation processes; in addition, nanocarriers can provide controlled and targeted drug release. This review describes the application of liposomes for the delivery of pharmaceutical actives to target MS. Firstly, MS is explained. Then, liposomes are described along with their preparation, characterization, and stability. The literature about the use of liposomes for the treatment of MS is then analyzed.

Synthesis and evaluation of transdermal rosuvastatin-loaded ultradeformable vesicles: Restoring the serum lipid profile in poloxamer 407-caused hyperlipidemia

The present study aimed to design, optimize and characterize rosuvastatin calcium-loaded transfersomes (ROS-TFs) for potential transdermal application and improved the antihyperlipidemic effect of ROS. ROS-TFs were prepared by the lipid thin film hydration method using soy phosphatidylcholine (SPC) to form lipid bilayers and tween 80 (T80) or sodium cholate (SC) as an edge activator (EA). The ROS-TFs were optimized for several parameters, including the proportions of SPC and EA, the particle size (PS) and the entrapment efficiency (EE%). The optimized formulation showed a PS of 169 ± 0.7 nm, zeta potential (ZP) of −19.05 ± 0.4 mV, polydispersity index (PDI) of 0.19 ± 0.02 and EE% of 72.71 ± 1.77. The optimized formulation was further incorporated into a Carbopol 940 gel to obtain a rosuvastatin calcium-loaded transfersomal gel (ROS-TFG) to prolong its residence time on skin. The resulting ROS-TFs exhibited sustained drug release followed by ROS-TFG after 2 h at a pH of 7.4. Skin permeation studies showed enhanced skin permeation of ROS-TFs compared to that of the plain drug gel at a pH of 7.4. In vivo antihyperlipidemic results demonstrated a significant improvement in the lipid profile of the ROS-TFG group in contrast to that of the plain drug gel group. Taken together, these findings indicate that ROS-TFs could be promising nanocarriers for transdermal drug delivery with enhanced antihyperlipidemic effects in the treatment of hyperlipidemia.

Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications

Employing small extracellular vesicles (EVs) as drug delivery vehicles presents a plethora of advantages over conventional drug delivery methods, including biological compatibility, engineering versatility for targeted delivery, and biodegradability. Therefore, strategies aimed at amplifying their therapeutic potential involve developing efficient, tissue-specific, and non-immunogenic delivery approaches. Despite rapid advancements in the realm of EVs as drug delivery systems in recent years, the availability of a high-yield, reproducible, and cost-effective source for EVs production and isolation remains a limiting factor for practical application. In this study, we isolated EVs from Saccharomyces cerevisiae (S.c) and loaded them with cargoes such as hsa-miR-143 (an apoptosis-inducing miRNA) or miR-H6 (a miRNA targeting HSV-1). We demonstrated the capability of these EVs to deliver microRNAs or even large mRNA to a variety of cell types. The therapeutic potential of S.c-derived EVs (S.c-EVs) was further evidenced by their ability to inhibit tumor growth in animal models. The S.c-EVs proved to be safe and non-immunogenic in vivo. Our results suggest that Saccharomyces cerevisiae represents a cost-effective source of extracellular vesicles, serving as nanocarriers for functional drug delivery in therapeutic applications.

Heparin-functionalized Cu-based metal-organic framework: An efficient active and passive targeting nanocarrier for anticancer doxorubicin drug delivery

Heparin-functionalized Cu-based metal-organic framework: An efficient active and passive targeting nanocarrier for anticancer doxorubicin drug delivery

Designing and Formulation of Nanocarriers for "Alzheimer's and Parkinson's" Early Detection and Therapy.

The potential of nanotechnology in advancing the diagnosis and treatment of neurodegenerative diseases is explored in this comprehensive literature review. The findings of these studies suggest that nanotechnology has the capacity to improve existing therapeutic approaches, create novel and safe compounds, and develop more precise imaging techniques and diagnostic methods for neurodegenerative diseases. With the emergence of the nanomedicine era, a new and innovative approach of diagnosing and treating these conditions has been introduced. Notably, the researchers' development of a nanocarrier drug delivery tool demonstrates immense potential compared to conventional therapy, as it maximizes therapeutic efficacy and minimizes undesirable as side effects.

A one-platform comparison study of brinzolamide-loaded liposomes, niosomes, transfersomes, and transniosomes for better management of glaucoma

Ocular drug delivery presents significant challenges due to various anatomical and physiological barriers. Ultradeformable vesicles have emerged as better vesicular systems for achieving deeper corneal penetration and enhanced ocular bioavailability. This research aims to develop a hybrid vesicular system with improved deformability and compare it to conventional vesicular carriers. The ultradeformable vesicle, termed “transniosomes,” is a combination of niosomes, liposomes, and transfersomes, loaded with brinzolamide as model drug. The brinzolamide-loaded transniosomes (BRZ-TN) was formulated and compared with different vesicular systems through in vitro, ex vivo, and in vivo characterizations. The optimized BRZ-TN demonstrated a vesicle size of 112.06 ± 4.13 nm and an entrapment efficiency of 93.63 ± 0.30 %. With a deformability index of 6.405, the BRZ-TN exhibited a permeability of 86.68 ± 2.51 % over 10 h, which is approximately 1.3 times higher than other conventional vesicular systems. Additionally, the BRZ-TN showed a drug flux of 0.247 ± 0.01 mg/cm2/h and an apparent permeability of 0.09 ± 1.21 cm/s. Pre-clinical experiments confirmed the superiority of the optimized BRZ-TN, achieving a 37 % reduction in intraocular pressure (IOP), post 6hr of administration, indicating its prolonged therapeutic effect and improved ocular bioavailability. The findings of this study suggest that transniosomes are superior to other carriers and hold great promise as a nanocarrier for ocular drug delivery.

Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.

Toward the Integration of Machine Learning and Molecular Modeling for Designing Drug Delivery Nanocarriers.

The pioneering work on liposomes in the 1960s and subsequent research in controlled drug release systems significantly advances the development of nanocarriers (NCs) for drug delivery. This field is evolved to include a diverse array of nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and more, each tailored to specific therapeutic applications. Despite significant achievements, the clinical translation of nanocarriers is limited, primarily due to the low efficiency of drug delivery and an incomplete understanding of nanocarrier interactions with biological systems. Addressing these challenges requires interdisciplinary collaboration and a deep understanding of the nano-bio interface. To enhance nanocarrier design, scientists employ both physics-based and data-driven models. Physics-based models provide detailed insights into chemical reactions and interactions at atomic and molecular scales, while data-driven models leverage machine learning to analyze large datasets and uncover hidden mechanisms. The integration of these models presents challenges such as harmonizing different modeling approaches and ensuring model validation and generalization across biological systems. However, this integration is crucial for developing effective and targeted nanocarrier systems. By integrating these approaches with enhanced data infrastructure, explainable AI, computational advances, and machine learning potentials, researchers can develop innovative nanomedicine solutions, ultimately improving therapeutic outcomes.

Nanotechnology-Based Drug Delivery Systems for Treating Acute Kidney Injury.

Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.

Rapamycin and Hyperoside-Co-loaded Macrophage Delivery System Enhanced Pulmonary Fibrosis Therapy by Autophagy Upregulation and Epithelial-to-Mesenchymal Transition Inhibition.

Pulmonary fibrosis is a lethal interstitial lung disease, for which current treatments are inadequate in halting its progression. A significant factor contributing to the development of fibrosis is insufficient autophagy, which leads to increased fibroblast proliferation and collagen deposition. However, treatments aimed at upregulating autophagy often cause further lung pathology due to the disruption of epithelial cell balance. In response, we have developed a novel macrophage delivery system loaded with an epithelial-to-mesenchymal transition inhibitor, hyperoside (HYP), and an autophagy inducer, rapamycin (RAP). This system targets the fibrotic areas of the lung through chemotaxis, releases liposomes via macrophage extracellular traps, and effectively inhibits fibroblast proliferation while restoring the alveolar structure through the combined effects of RAP and HYP, ultimately reducing lung pathology without causing systemic toxicity. Our findings not only highlight a promising method to enhance autophagy-based treatments for pulmonary fibrosis but also demonstrate the potential of macrophages as effective nanocarriers for drug delivery.

Recent Advances in the Use of Vitamin D Organic Nanocarriers for Drug Delivery.

Nanotechnology, now established as a transformative technology, has revolutionized medicine by enabling highly targeted drug delivery. The use of organic nanocarriers in drug delivery systems significantly enhances the bioavailability of vitamins and their analogs, thereby improving cellular delivery and therapeutic effects. Vitamin D, known for its crucial role in bone health, also influences various metabolic functions, such as cellular proliferation, differentiation, and immunomodulation, and is increasingly explored for its anticancer potential. Given its versatile properties and biocompatibility, vitamin D is an attractive candidate for encapsulation within drug delivery systems. This review provides a comprehensive overview of vitamin D synthesis, metabolism, and signaling, as well as its applications in customized drug delivery. Moreover, it examines the design and engineering of organic nanocarriers that incorporate vitamin D and discusses advances in this field, including the synergistic effects achieved through the combination of vitamin D with other therapeutic agents. By highlighting these innovations, this review provides valuable insights into the development of advanced drug delivery systems and their potential to enhance therapeutic outcomes.

Magnetized electroosmotic drug delivery of Au-SiO2 nanocarriers through blood-based jeffrey hybrid nanofluid in a microchannel: Caputo Fabrizio derivative modeling

Fractional calculus is emerging as a promising field to overcome the intricacies inherent in biological systems that prevent conventional techniques from producing optimal results. The present research emphasizes the impact of thermal radiation, chemical reactions, and radiation absorption on an electroosmotic magnetohydrodynamic (MHD) blood-based Jeffrey hybrid nanofluid flow in a microchannel, employing the novel Caputo-Fabrizio fractional calculus approach. This study is carried out on two models: ramped and constant boundary conditions with distinct zeta potentials. The graphs are drawn with the help of MATLAB software. Our results demonstrate that the fractional order significantly influences the drug dispersion, and for α=0.9 (fractional parameter), the blood flow becomes wavy. The presence of nanoparticles improves drug transport, hence enhancing the drug concentration in proximity to the target site. For α=0.1, the Jeffrey nanofluid with ramped conditions shows the highest velocity enhancement in the case of pressure-driven, natural convective flow. Electroosmotic force facilitates fluid flow and enhances drug transport efficiency. For Ha < 4, the blood velocity decreases in the vicinity of the plate y = 0, and reverse behavior is observed as it passes y = 0.5, which can aid in effective drug delivery. At y = 0, the heat transfer rate increases by a maximum of 199.18 % while skin friction decreases to 3.07 %, aiding in maintaining medications at the desired temperature and improving drug delivery efficiency. The temperature and velocity of the blood hybrid nanofluid are maximized under ramping wall settings compared to constant wall conditions.