Optimization Of Delivery System Research Articles

Advancing Cancer Therapy: The Role of KIF20A as a Target for Inhibitor Development and Immunotherapy.

The analysis begins with a detailed examination of the gene expression and protein structure of KIF20A, highlighting its interaction with critical cellular components that influence key processes such as Golgi membrane transport and mitotic spindle assembly. The primary focus is on the development of specific KIF20A inhibitors, detailing their roles and the challenges encountered in enhancing their efficacy, such as achieving specificity, overcoming tumor resistance, and optimizing delivery systems. Additionally, it delves into the prognostic value of KIF20A across multiple cancer types, emphasizing its role as a novel tumor-associated antigen, which lays the groundwork for the development of targeted peptide vaccines. The therapeutic efficacy of these vaccines as demonstrated in recent clinical trials is discussed. Future directions are proposed, including the integration of precision medicine strategies to personalize treatments and the use of combination therapies to improve outcomes. By concentrating on the significant potential of KIF20A as both a direct target for inhibitors and an antigen in cancer vaccines, this review sets a foundation for future research aimed at harnessing KIF20A for effective cancer treatment.

Investigating the impact of 2-OHOA-embedded liposomes on biophysical properties of cancer cell membranes via Laurdan two-photon microscopy imaging

2-Hydroxyoleic acid (2-OHOA) has gained attention as a membrane lipid therapy (MLT) anti-cancer drug. However, in the viewpoint of anti-cancer drug, 2-OHOA shows poor water solubility and its effectiveness still has space for improvement. Thus, this study aimed to overcome the problems by formulating 2-OHOA into liposome dosage form. Furthermore, in the context of MLT reagents, the influence of 2-OHOA on the biophysical properties of the cytoplasmic membrane remains largely unexplored. To bridge this gap, our study specifically focused the alterations in cancer cell membrane fluidity and lipid packing characteristics before and after treatment. By using a two-photon microscope and the Laurdan fluorescence probe, we noted that liposomes incorporating 2-OHOA induced a more significant reduction in cancer cell membrane fluidity, accompanied by a heightened rate of cellular apoptosis when compared to the non-formulated 2-OHOA. Importantly, the enhanced efficacy of 2-OHOA within the liposomal formulation demonstrated a correlation with its endocytic uptake mechanism. In conclusion, our findings underscore the significant influence of 2-OHOA on the biophysical properties of cancer plasma membranes, emphasizing the potential of liposomes as an optimized delivery system for 2-OHOA in anti-cancer therapy.

A redox homeostasis disruptor based on a biodegradable nanoplatform for ultrasound (US) imaging-guided high-performance ferroptosis therapy of tumors

ABSTRACT The synergistic disruption of intracellular redox homeostasis through the combination of ferroptosis/gas therapy shows promise in enhancing the antitumor efficacy. However, the development of an optimal delivery system encounters significant challenges, including effective storage, precise delivery, and controlled release of therapeutic gas. In this study, we propose the utilization of a redox homeostasis disruptor that is selectively activated by the tumor microenvironment (TME), in conjunction with our newly developed nanoplatforms (MC@HMOS@Au@RGD), for highly efficient ferroptosis therapy of tumors. The TME-triggered degradation of HMOS initiates the release of MC and AuNPs from the MC@HMOS@Au@RGD nanoplatform. The released MC subsequently reacts with endogenous hydrogen peroxide (H2O2) and H+ to enable the on-demand release of CO gas, leading to mitochondrial damage. Simultaneously, the released AuNPs exhibit GOx-like activity, catalyzing glucose to generate gluconic acid and H2O2. This process not only promotes the decomposition of MnCO to enhance CO production but also enhances the Fenton-like reaction between Mn2+ and H2O2, generating ROS through the modulation of the H+ and H2O2-enriched TME. Moreover, the generation of CO bubbles enables the monitoring of the ferroptosis treatment process through ultrasound (US) imaging. The efficacy of our prepared MC@HMOS@Au@RGD disruptors in ferroptosis therapy is validated through both in vitro and in vivo experiments.

Transdermal Delivery of Recombinant Human Growth Hormone by Liposomal Gel for Skin Photoaging Therapy.

Human growth hormone (hGH) has emerged as a promising therapeutic agent to prevent and treat skin photoaging. However, the success of hGH therapy largely lies in the availability of an optimal delivery system that enables the efficient delivery of hGH to the dermal layer of the skin. Here, we report a delivery system of hyaluronic acid/liposome-gel-encapsulated hGH (HA/HL-Gel) that can transdermally deliver hGH into the skin for hGH-based photoaging therapy through the upregulation of collagen type I (collagen-I). Specifically, hGH-liposomes were prepared by ethanol injection and then modified with HA to achieve specific targeting. The best formulation of HA/hGH-liposomes (HA/HL) had a high encapsulation efficiency (about 20%), with a size of 180 ± 1.2 nm. The optimized HA/HL was further incorporated into the carbomer gel to form an HA/HL-Gel. The biological activity of HA/HL on human dermal fibroblasts (HDFs) was confirmed by the elevated expression level of collagen-I through the enhanced local formation of insulin-like growth factor-1 (IGF-1) in the photoaging model. Moreover, HA/HL-Gel reduced ultraviolet (UV)-induced erythema and wrinkle formation. Meanwhile, immunohistochemical staining further showed higher levels of collagen-I in the HA/HL-Gel group compared to other groups tested. Taken together, these results demonstrate that HA/HL-Gel treatment could significantly ameliorate skin photoaging and thus may be used as a clinical potential for antiaging therapy.

A novel peptide-drug conjugate for glioma-targeted drug delivery

The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel “Y”-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.

Stability and Bioaccessibility of Quercetin-Enriched Pickering Emulsion Gels Stabilized by Cellulose Nanocrystals Extracted from Rice Bran.

To investigate the optimal delivery system of quercetin, in this paper, cellulose nanocrystals (CNCs) extracted from rice bran were used to stabilize the Pickering emulsion and Pickering emulsion gels (PEGs) with quercetin. To compare the emulsion properties, stability, antioxidation activity, encapsulation rate, and bioaccessibility of the quercetin, four emulsions of CNC Pickering emulsion (C), CNC Pickering emulsion with quercetin (CQ), CNC Pickering gel emulsion (CG), and CNC Pickering gel emulsions with quercetin (CQG) were prepared. All four emulsions exhibited elastic gel network structure and good stability. The quercetin significantly reduced the particle size, increased the stability, and improved the antioxidant capacity of CQ and CQG. Compared to C and CG, the ABTS+ radical scavenging capacities of CQ and CQG were respectively enhanced by 46.92% and 3.59%. In addition, CQG had a higher encapsulation rate at 94.57% and higher bioaccessibility (16.17) compared to CQ. This study not only indicated that CNC from rice bran could be exploited as an excellent stabilization particle for Pickering emulsions, but also provided a highly stable and bioaccessible delivery system for water-insoluble functional active factors.

A continuous approximation approach to integrated truck and drone delivery systems

Home package delivery by drones as an alternative or complement to traditional delivery by trucks is attracting considerable attention from the commercial sector as well as academia. While drone delivery may offer considerable benefits, the fundamental issues of how best to deploy drones for small package delivery are still not well understood. Unlike most studies in the literature that consider either truck-drone tandems or drone standalone delivery operations, our research provides a strategic analysis for the optimal design of an integrated drone delivery system in which customers in a service region can be served by a combination of truck-drone (TD) delivery, drone-only (DO) delivery, and truck-only (TO) delivery. We formulate and optimize continuous approximation models to identify the optimal delivery service combination that minimizes the total delivery costs including truck and drone operating and stop costs. We evaluate the impact of a wide range of operating characteristics and delivery environments on the optimal delivery system and the benefits of using drones. Our results suggest that an optimal delivery system design often uses a mix of DO and TD, but TD is the dominant delivery service in most scenarios. The magnitude of the cost savings afforded by the use of drones, relative to truck-only delivery, can be large but strongly depends on the values of key parameters.

Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy.

Cataract surgery interventions are constantly increasing, particularly among adult and elderly patients. This type of surgery can lead to inflammatory states of the ocular anterior segment (AS), usually healed via postoperative treatment with dexamethasone (DEX)-containing eye drops. The application of eye drops is challenging due to the high number of daily administrations. In this study, mucoadhesive nanoparticles (NPs) were formulated to improve the residence time of DEX on the corneal mucosa, enhancing the drug's solubility and bioavailability. The NPs were generated using an ionotropic gelation technique, exploiting the interaction between the cationic group of chitosan (CS) and the anionic group of sulfobutylether-β-cyclodextrin (SBE-β-CD). The formation of the inclusion complex and its stoichiometry were studied through phase solubility studies, Job's plot method, and Bi-directional transport studies on MDCKII-MDR1. The obtained NPs showed good chemical and physical characteristics suitable for drug loading and subsequent testing on animal mucosa. The DEX-loaded CS/SBE-β-CD NPs exhibited a prolonged residence time on animal mucosa and demonstrated enhanced drug permeability through the corneal membrane, showing a sustained release profile. The developed NPs posed no irritation or toxicity concerns upon local administration, making them an optimal and innovative drug delivery system for inflammatory AS diseases treatment.

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects.

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.

A Critical Appraisal of the Protective Activity of Polyphenolic Antioxidants against Iatrogenic Effects of Anticancer Chemotherapeutics.

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, and cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, and curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticarcinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have also been investigated for their counteraction against the adverse effects of common anticancer chemotherapeutics. This review evaluates the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in polyphenols' metabolic stability and bioavailability, through the implementation of nanotechnologies that are currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy.

Injectable thermosensitive selenium-containing hydrogel as mesenchymal stem cell carrier to improve treatment efficiency in limb ischemia

Limb ischemia is a refractory disease characterized by persistent inflammation, insufficient angiogenesis, and tissue necrosis. Although mesenchymal stem cells (MSCs) have shown potential for treating limb ischemia, their therapeutic effects are limited by low engraftment rates. Therefore, developing an optimal MSC delivery system that enhances cell viability is imperative. Selenium, known for its cytoprotective properties in various cell types, offers a potential strategy to enhance therapeutic effect of MSCs. In this study, we evaluated the cytoprotective effects of selenium on MSCs, and developed an injectable thermosensitive selenium-containing hydrogel based on PLGA-PEG-PLGA triblock copolymer, as a cell carrier to improve MSC viability after engraftment. The biocompatibility, biodegradability, and cytoprotective capabilities of selenium-containing hydrogels were assessed. Furthermore, the therapeutic potential of MSCs encapsulated within a thermosensitive selenium-containing hydrogel in limb ischemia was evaluated using cellular and animal experiments. Selenium protects MSCs from oxidative damage by upregulating GPX4 through a transcriptional mechanism. The injectable thermosensitive selenium-containing hydrogel exhibited favorable biocompatibility, biodegradability, and antioxidant properties. It can be easily injected into the target area in liquid form at room temperature and undergoes gelation at body temperature, thereby preventing the diffusion of selenium and promoting the cytoprotection of MSCs. Furthermore, MSCs encapsulated within the selenium-containing hydrogel effectively inhibited macrophage M1 polarization while promoting macrophage M2 polarization, thus accelerating angiogenesis and restoring blood perfusion in ischemic limbs. This study demonstrated the potential of an injectable thermosensitive selenium-containing hydrogel as a promising method for MSC delivery. By addressing the challenge of low retention rate, which is a major obstacle in MSC application, this strategy effectively improves limb ischemia.

DNA Vaccines: Their Formulations, Engineering and Delivery.

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns.

ISX9 loaded thermoresponsive nanoparticles for hair follicle regrowth

There is a high demand for an optimal drug delivery system to treat androgenetic alopecia. Topical application of ISX9, which is a neurogenesis inducer, has been found to stimulate hair follicle (HF) regrowth by upregulating the Wnt/β-catenin signaling pathway, an essential pathway involved in initiating HF growth and development. In the present study, a temperature-sensitive, biopolymer-based, biocompatible, and eco-friendly drug-delivery system was synthesized. This system comprised chitosan-grafted poly(glycidyl methacrylate-co-N-isopropyl acrylamide) (Poly(GMA-co-NIPAAm)@CS-PGNCS) as the shell component and PF127 as the core polymer. The hydrophobic nature of the PF127 block copolymer efficiently dissolved the partially water-soluble drug, ISX9, and the thermos-responsive shell polymer effectively released the drug at a definite skin temperature. The optimized spherical nanoparticles demonstrated the lowest critical solution temperature (LCST) at 32 ± 2 °C with a diameter of 100–250 nm, which delivered encapsulated ISX9 with greater precision than topical ISX9. In a series of in vivo experiments, we demonstrated that ISX9-coated TBNPs upregulated the expression of β-catenin, active β-catenin, Wnt target genes, stemness marker genes, proliferating cell nuclear antigen, HF stem cell markers, and HF markers including VEGF, TGF, and IGF-1 more effectively than topical ISX9. These results suggest that TBNPs could be employed as a platform for effective transdermal delivery of various hydrophobic drugs.

A novel reverse micelle based cationic double nanoemulsion as a potential nanoplatform for enhancing the anitglucomal activity of betaxolol hydrochloride; formulation, in vitro characterization, ex vivo permeation and in vivo pharmacodynamic evaluation in glaucomatous rabbits’ eyes

Glaucoma is one of the most common causes of irreversible vision loss worldwide. The hydrophilic nature of the anti-glaucoma drug Betaxolol hydrochloride (BH) limits its ocular permeation necessitating repeated dosing. This can reduce patient compliance and increase the risk of experiencing adverse side effects. Our research is the first to encapsulate BH into reverse micelle-based cationic double W1/O/W2 nanoemulsions (RM-CDNEs) as a new platform capable of enhancing both the corneal permeability and IOP lowering efficacy of this drug. BH-loaded RM-CDNEs were prepared by a modified two-step emulsification method using sonication technique and applying 24 full factorial design to assess the impact of formulation variables and select the optimal delivery system. The in vitro drug-release, ex vivo permeation and in vivo performance of this novel nanocarrier were also assessed. The optimal delivery system (RM-CDNE 10) has mean DS, PDI, ZP and entrapment efficiency of 46.53 ± 1.30 nm, 0.217 ± 0.02, +40.9 ± 5.04 mV and 95.1 ± 2.44 %, respectively. A 90.77 % of drug was released over 7h. RM-CDNE 10 showed 2.5-fold increase in ex vivo corneal BH permeation with a prolonged IOP reduction of 58.77 % ± 1.18 % and AUC0-48 of 2537.82 ± 12.8%h. While, the marketed product (Epitaxol®) had only 33.63 ± 1.54 % IOP reduction with AUC0–48 h of 823.14 ± 3.67%h when tested in rabbits (P ≤ 0.05). Histopathological and Draize irritation studies confirmed that RM-CDNEs were non-irritant. These findings proved that the novel BH-loaded RM-CDNEs system improved the outcomes for patients suffering from glaucoma and thus decreasing the liability for disease progression into blindness.

A targeted drug delivery system based on E. coli ghost for inhibiting non-Hodgkin’s lymphoma

Doxorubicin (DOX) is extensively utilized in the treatment of aggressive lymphomas, while its significant toxic side effects hamper its clinical application. Hence, there is an urgent need for a safe and effective antilymphoma drug delivery system at this stage. This study successfully developed an optimal drug delivery system (R-PEG@BGs-DOX) to safe and efficient delivery of DOX to non-Hodgkin's lymphoma site. The R-PEG@BGs-DOX was prepared by modifying polyethylene glycol (PEG) and Rituximab (R) onto the surface of bacterial ghosts (BGs), which were obtained through NaOH treatment of E. coli BL21 with modulation to achieve target structures. The prepared R-PEG@BGs exhibited efficient loading of DOX, demonstrating excellent targeting properties. The R-PEG@BGs-DOX can significantly inhibit the growth of non-Hodgkin's lymphoma cells while showing minimal toxic side effects on normal tissues. These results strongly suggest that R-PEG@BGs-DOX holds great promise as an intelligent, safe, and effective drug delivery system for anti-lymphoma treatment.

Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy.

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.

Defining Personas of People Living with Chronic Pain: An Ethnographic Research Study.

Pain is the leading reason for which people seek medical care in the United States, and chronic pain (CP) affects approximately 50 million people in the US Pain perception is deeply personal, is highly correlated with behavioral and emotional disorders, and is greatly influenced by physiological and environmental factors. The patient-provider relationship can have profound implications for clinical outcomes within the context of treating CP. However, limited access to pain specialists, the complex nature of many CP-causing conditions, the absence of instruments for objective pain measurement, and the need to foster a trust-based patient-provider relationship throughout treatment pose unique challenges. To support a more optimal CP care delivery system that leverages a healthy therapeutic patient-provider relationship, we systematically gathered deeper knowledge of the behaviors, interpersonal dynamics, home environment, values, and mindsets of people who experience CP. We employed ethnographic research methods to collect and analyze data on views, habits, strategies, attitudes, and life circumstances of a range of participants living with CP. We aggregated, analyzed, and summarized participant data to identify trends and similarities. Our findings suggest that patients can be broadly categorized into five predominant pain typologies, or "personas", which are characterized by respective symptom durations, care management preferences, values, communication styles, and behaviors. Identifying CP personas may enhance the ability to personalize CP care and help foster more robust therapeutic relationships, which may lead to greater trust, improved patient satisfaction, and better clinical outcomes.

A dispersion-corrected DFT calculation on encapsulation of favipiravir drug used as antiviral against COVID-19 into carbon-, boron-, and aluminum-nitride nanotubes for optimal drug delivery systems combined with molecular docking simulations.

The online version contains supplementary material available at 10.1007/s11224-023-02182-4.

Shear-Triggered Release of Lipid Nanoparticles from Tissue-Mimetic Hydrogels.

Shear forces are involved in many cellular processes and increase remarkably in the case of cardiovascular diseases in the human body. While various stimuli, such as temperature, pH, light, and electromagnetic fields, have been considered for on-demand release, developing drug delivery systems that are responsive to physiological-level shear stresses remains as a challenge. For this purpose, liposomes embedded in hydrogel matrices are promising as they can dynamically engage with their environment due to their soft and deformable structure. However, for optimal drug delivery systems, the interaction between liposomes and the surrounding hydrogel matrix, and their response to the shear should be unraveled. Here, we used unilamellar DMPG liposomes as drug nanocarriers and polyethylene (glycol) diacrylate (PEGDA) hydrogels having different elasticities, from 1Pa to 180Pa, as extracellular matrix (ECM)-mimetic matrices to understand shear-triggered liposome discharge from hydrogels. The presence of liposomes provides hydrogels with temperature-controlled water uptake which is sensitive to membrane microviscosity. By systematically applying shear deformation from linear to nonlinear deformation regimes, we modulate the liposome release under transient and cyclic stimuli. Considering that shear force is commonly encountered in biofluid flow, these results will provide fundamental basis for rational design of shear-controlled liposomal drug delivery systems. This article is protected by copyright. All rights reserved.

Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies.

Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Ab─a broadly neutralizing Ab against HIV-1─maintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.