Stimuli-responsive Nanoparticles Research Articles

Development of a manganese complex hyaluronic acid hydrogel encapsulating stimuli-responsive Gambogic acid nanoparticles for targeted Intratumoral delivery

Gambogic acid is a natural compound with anticancer properties and is effective for many tumors. But its low water solubility and dose-dependent side effects limit its clinical application. This study aims to develop a novel drug delivery system for intratumoral delivery of gambogic acid. In our experimental study, we propose a new method for encapsulating gambogic acid nanoparticles using a manganese composite hyaluronic acid hydrogel as a carrier, designed for targeted drug delivery to tumors. The hydrogel delivery system is synthesized through the coordination of hyaluronic acid-dopamine (HA-DOPA) and manganese ions. The incorporation of manganese ions serves three purposes:1.To form cross-linked hydrogels, thereby improving the mechanical properties of HA-DOPA.2.To monitor the retention of hydrogels in vivo in real-time using magnetic resonance imaging (MRI).3.To activate the body's immune response. The experimental results show that the designed hydrogel has good biosafety, in vivo sustained release effect and imaging tracking ability. In the mouse CT26 model, the hydrogel drug-loaded group can better inhibit tumor growth. Further immunological analysis shows that the drug-loaded hydrogel group can stimulate the body's immune response, thereby better achieving anti-tumor effects. These findings indicate the potential of the developed manganese composite hyaluronic acid hydrogel as an effective and safe platform for intratumoral drug delivery. The amalgamation of biocompatibility, controlled drug release, and imaging prowess positions this system as a promising candidate for tumor treatment.

Facile synthesis and polymerization of 1,4,5-oxadithiepan-2-one for disulfide-based redox-responsive drug delivery

Chemotherapeutic drugs have been shown to be promising for the treatment of tumors, however, they are associated with several disadvantages including low aqueous solubility, non-specificity, and poor plasma stability. Hence, they accumulate in the health organs and create several adverse effects. Drug encapsulated stimuli-responsive nanoparticles bearing redox-responsive disulfide linkages have emerged as promising delivery vehicle to address these limitations. A glutathione (GSH) responsive disulfide-based drug delivery system based on a polyethylene glycol methyl ether (PEGME) and a polydisulfide (PDS) diblock copolymer has been developed. The cyclic lactone containing a disulfide link, 1,4,5-oxadithiepan-2-one, was prepared using a thiol-free method utilizing the reaction of 2-bromoethyl bromoacetate with sodium disulfide. Ring-opening polymerization (ROP) of 1,4,5-oxadithiepan-2-one using 1-butanol in the presence of Sn(oct)2 generated the homopolymer PDS whereas the diblock copolymer PEGME-b-PDS was obtained when PEGME was used as a macroinitiator. In aqueous solution, PEGME-b-PDS self-assembled into spherical-shaped micelles with a hydrodynamic radius of 146 and 116 nm as measured by Field-emission Scanning Electron Microscopy (FESEM) and Dynamic Light Scattering (DLS), respectively. At pH = 7.4, a Doxorubicin (DOX) loaded PEGME-b-PDS micelle showed a cumulative release of ∼98.2, ∼9.9, and ∼1.9 % in presence of 2 mM, 2 μM DTT and in absence of DTT, respectively clearly demonstrating the redox responsiveness of the PDS block. The best fit of kinetic data using with the Korsmeyer-Peppas model suggests a Fickian diffusion as well as chain-relaxation controlled drug release process. DOX loaded micelles and free DOX displayed similar cytotoxicity towards both 4T1 and MCF-7 cells indicating that the encapsulation inside the micelle did not affect the anticancer efficacy of the drug. The drug loaded micelle showed higher cellular uptake than free DOX in both 4T1 and MCF-7 lines and lower cellular uptake than free DOX in 3T3-L1 cell lines. This polymeric micellar nanoparticle may be further exploited for encapsulation of other hydrophobic drugs.

Harnessing the Power of Stimuli-Responsive Nanoparticles as an Effective Therapeutic Drug Delivery System.

The quest for effective and reliable methods of delivering medications, with the aim of improving delivery of therapeutic agent to the intended location, has presented a demanding yet captivating field in biomedical research. The concept of smart drug delivery systems is an evolving therapeutic approach, serving as a model for directing drugs to specific targets or sites. These systems have been developed to specifically target and regulate the administration of therapeutic substances in a diverse array of chronic conditions, including periodontitis, diabetes, cardiac diseases, inflammatory bowel diseases, rheumatoid arthritis, and different cancers. Nevertheless, numerous comprehensive clinical trials are still required to ascertain both the immediate and enduring impacts of such nanosystems on human subjects. This review delves into the benefits of different drug delivery vehicles, aiming to enhance comprehension of their applicability in addressing present medical requirements. Additionally, it touches upon the current applications of these stimuli-reactive nanosystems in biomedicine and outlines future development prospects.

Stimuli-triggered Self-Assembly of Gold Nanoparticles: Recent Advances in Fabrication and Biomedical Applications.

Gold nanoparticles have been widely used in engineering, material chemistry, and biomedical applications owing to their ease of synthesis and functionalization, localized surface plasmon resonance (LSPR), great chemical stability, excellent biocompatibility, tunable optical and electronic property. In recent years, the decoration and modification of gold nanoparticles with small molecules, ligands, surfactants, peptides, DNA/RNA, and proteins have been systematically studied. In this review, we summarize the recent approaches on stimuli-triggered self-assembly of gold nanoparticles and introduce the breakthrough of gold nanoparticles in disease diagnosis and treatment. Finally, we discuss the current challenge and future prospective of stimuli-responsive gold nanoparticles for biomedical applications.

Micelle-based nanoparticles with stimuli-responsive properties for drug delivery

Abstract Cancer treatment often causes adverse effects and toxicity, as chemotherapy drugs affect both cancerous and healthy cells. Scientists seek to target tumor cells specifically and minimize harm to normal cells. Smart nanoparticles (NPs) are a modern technique that can release drugs when triggered by internal or external stimuli, such as temperature, pH, ultrasound, etc. This review covers stimuli-responsive micelle-based nanoparticles (SRM-NPs), a promising drug delivery platform that can enhance drug efficacy and reduce toxicity. It discusses the recent developments and applications of SRM-NPs, their responsiveness to different stimuli, and their potential to overcome drug resistance and adaptive responses. It also addresses the challenges and issues related to their stability, reproducibility, biocompatibility, safety, and optimization. The study concludes that SRM-NPs have great potential for drug delivery, but more research and development are needed to improve their clinical utility.

Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting.

A dual stimuli-responsive nanocarrier was developed from smart biocompatible chitosan and soluplus graft copolymers. The copolymerization was investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier transform infrared (FTIR). The optimized chitosan-soluplus nanoparticles (CS-SP NPs) were further used for the encapsulation of a poorly water-soluble anticancer drug. Tamoxifen citrate (TC) was used as the model drug and it was loaded in CS-SP NPs. TC CS-SP NPs were characterized in terms of particle size, zeta potential, polydispersity, morphology, encapsulation efficiency, and physical stability. The nanoparticles showed homogenous spherical features with a size around 94 nm, a slightly positive zeta potential, and an encapsulation efficiency around 96.66%. Dynamic light scattering (DLS), in vitro drug release, and cytotoxicity confirmed that the created nano-system is smart and exhibits pH and temperature-responsive behavior. In vitro cellular uptake was evaluated by flow cytometry and confocal microscopy. The nanoparticles revealed a triggered increase in size upon reaching the lower critical solution temperature of SP, with 70% of drug release at acidic pH and 40 °C within the first hour and a 3.5-fold increase in cytotoxicity against MCF7 cells incubated at 40 °C. The cellular uptake study manifested that the prepared nanoparticles succeeded in delivering drug molecules to MCF7 and MDA-MB-231 cells. In summary, the distinctive characteristics provided by these novel CS-SP NPs result in a promising nano-platform for effective drug delivery in cancer treatment.

Dual stimuli-responsive upconversion nanoparticle-poly-N-isopropylacrylamide/DNA core-shell microgels.

Stimuli-responsive upconversion nanoparticle (UCNP)-poly-N-isopropylacrylamide (pNIPAM)/DNA core-shell microgels with tunable sizes and programmable functions have been prepared. Thanks to the near-infrared (NIR)-responsive UCNP cores and thermosensitive polymeric shells, functional DNA-incorporated microgels with high DNA activity and loading efficiency are obtained, and the activity of the loaded DNA structures can be smartly regulated by NIR illumination and temperature simultaneously.

Stimuli-responsive nanoparticle self-assembly at complex fluid interfaces: a new insight into dynamic surface chemistry.

The self-assembly of core/shell nanoparticles (NPs) at fluid interfaces is a rapidly evolving area with tremendous potential in various fields, including biomedicine, display devices, catalysts, and sensors. This review provides an in-depth exploration of the current state-of-the-art in the programmed design of stimuli-responsive NP assemblies, with a specific focus on inorganic core/organic shell NPs below 100 nm for their responsive adsorption properties at fluid and polymer interfaces. The interface properties, such as ligands, charge, and surface chemistry, play a significant role in dictating the forces and energies governing both NP-NP and NP-hosting matrix interactions. We highlight the fundamental principles governing the reversible surface chemistry of NPs and present detailed experimental examples in the following three key aspects of stimuli-responsive NP assembly: (i) stimuli-driven assembly of NPs at the air/liquid interface, (ii) reversible NP assembly at the liquid/liquid interface, including films and Pickering emulsions, and (iii) hybrid NP assemblies at the polymer/polymer and polymer/water interfaces that exhibit stimuli-responsive behaviors. Finally, we address current challenges in existing approaches and offer a new perspective on the advances in this field.

A highly tuneable inverse emulsion polymerization for the synthesis of stimuli-responsive nanoparticles for biomedical applications.

Polymeric nanomaterials have seen widespread use in biomedical applications as they are highly tuneable to achieve the desired stimuli-responsiveness, targeting, biocompatibility, and degradation needed for fields such as drug delivery and biosensing. However, adjustments to composition and the introduction of new monomers often necessitate reoptimization of the polymer synthesis to achieve the target parameters. In this study, we explored the use of inverse emulsion polymerization to prepare a library of polymeric nanoparticles with variations in pH and temperature response and examined the impact of overall batch volume and the volume of the aqueous phase on nanoparticle size and composition. We were able to prepare copolymeric nanoparticles using three different nonionic and three different anionic comonomers. Varying the non-ionizable comonomers, acrylamide (AAm), 2-hydroxyethyl methacrylate, and N-isopropylacrylamide (NIPAM), was found to alter the mass percentage of methacrylic acid (MAA) incorporated (from 26.7 ± 3.5 to 45.8 ± 1.8 mass%), the critical swelling pH (from 5.687 ± 0.194 to 6.637 ± 0.318), and the volume swelling ratio (from 1.389 ± 0.064 to 2.148 ± 0.037). Additionally, the use of NIPAM was found to allow for temperature-responsive behavior. Varying the ionizable comonomers, MAA, itaconic acid, and 2-acrylamido-2-methylpropane sulfonic acid (AMPSA), was found to significantly alter the critical swelling pH and, in the case of AMPSA, remove the pH-responsive behavior entirely. Finally, we found that for the base P(AAm-co-MAA) formulation, the pH-responsive swelling behavior was independent of the scale of the reaction; however, variations in the aqueous volume relative to the volume of the continuous phase significantly affected both the nanoparticle size and the critical swelling pH.

PH stimulus-responsive hybrid nanoparticles: A system designed for follicular delivery of brazilian plant-derived 5-alpha-reductase enzyme inhibitors

The 5-alpha-reductase enzyme, present in pilosebaceous units, plays a crucial role in the appearance of cutaneous hyperandrogenism manifestations (hirsutism, acne, and androgenetic alopecia). Its inhibition is an excellent strategy to reverse these conditions. Given the limitations of existing treatments, with transient effects and delayed therapeutic response, as well as the possibility of causing undesirable side effects, this study sought to develop new drug delivery systems to overcome these limitations. In other words, innovative stimuli-responsive hybrid nanoparticles were synthesized using silica/natural polysaccharides, encapsulating 5-alpha-reductase enzyme inhibitors derived from the plant Stryphnodendron adstringens (Mart.) Coville (commonly known as 'Barbatimão'). Silica core was synthesized by the modified Stöber method. The pH responsive polysaccharides used to coat the porous silica cores were chitosan, and sodium alginate, this coating was carried out using the Layer-by-Layer technique. The hybrid nanoparticles were characterized at molecular and physical–chemical levels. Furthermore, encapsulation efficiency, pH-dependent release behavior, and cytotoxicity were evaluated. Amorphous mesoporous structure with adequate size for follicular delivery (between 300 and 600 nm) in addition to effective phytocompound loading capacity, above 80 % was obtained. Based on the release studies, it was possible to observe pH responsiveness. The ethyl acetate fraction (EAF) obtained from “Barbatimão” bark extract was released in a controlled and more efficient manner by the alginate-coated nanoparticle (SNP_EAF_SA) at pH 7.4, which corresponds to the pH at the deepest area of hair follicles. Furthermore, SNP_EAF_SA proved to be less cytotoxic compared to EAF and chitosan-coated hybrid nanoparticles (SNP_EAF_CH). Characterization, release, and cytotoxicity results indicate that SNP_EAF_SA is a promising system for on-demand follicular delivery of antiandrogenic actives contained in EAF.

Temperature-Modulated Reversible Clustering of Gold Nanorods Driven by Small Surface Ligands.

Temperature-modulated colloidal phase of plasmonic nanoparticles is a convenient playground for resettable soft-actuators or colorimetric sensors. To render reversible clustering under temperature change, bulky ligands are required, especially if anisotropic morphologies are of interest. This study showcases thermoresponsive gold nanorods by employing small surface ligands, bis (p-sulfonatophenyl) phenyl-phosphine dihydrate dipotassium salt (BSPP) and native cationic surfactant. Temperature-dependent analysis in real-time allowed to describe the structural features (interparticle distance and cluster size) as well as thermal parameters, melting and freezing temperatures. These findings suggest that neither covalent Au-S bonds nor bulky ligands are required to obtain a robust thermoresponsive system based on anisotropic gold nanoparticles, paving the way to stimuli-responsive nanoparticles with a wide range of sizes and geometries.

Dispersion of silica nanoparticles in water/ethanol/PEG mixtures for stimuli-responsive aggregation to prepare improved fused silica glass

The preparation of bulk-fused silica glass using stimuli-responsive silica nanoparticle (SiNP) aggregation methods is a promising research topic. For instance, the use of a SiNP/polyethylene glycol (PEG)/polyvinyl butyral (PVB) system for thermoplastic nanocomposite preparation, followed by heat-treatment sintering, has emerged as a highly precise and scalable method for obtaining fused silica glass with a short processing time. In this study, transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and rheological analysis were used to investigate the dispersion of SiNPs in water, ethanol, water/ethanol, and water/ethanol/PEG mixtures. Furthermore, we investigated the effect of the different solvents on regulating external stimuli in the preparation of a SiNP slurry. Our results indicate that water/ethanol mixtures have a greater ability to obtain dispersed and thin slurries than water or ethanol alone, while the inclusion of PEG can further enhance this effect.The feedstocks obtained by this method is favorable for obtaining defect-free fused silica glass. In addition, agglomerates formed by SiNPs in a liquid environment can be rearranged and partially disassembled under the action of mechanical (shear) forces. Finally, optical profilometry tests showed that the sintered fused silica glass exhibited good surface quality replication, with a roughness Sa of only 148 nm. The finding in this study provides an idea for the preparation of commercial slurry for sintering fused silica glass.

Nanoparticle-mediated active and passive drug targeting in oral squamous cell carcinoma: current trends and advances.

Oral squamous cell carcinoma (OSCC) is an invasive and highly malignant cancer with significant morbidity and mortality. Existing treatments including surgery, chemotherapy and radiation have poor overall survival rates and prognosis. The intended therapeutic effects of chemotherapy are limited by drug resistance, systemic toxicity and adverse effects. This review explores advances in OSCC treatment, with a focus on lipid-based platforms (solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrids, cubosomes), polymeric nanoparticles, self-assembling nucleoside nanoparticles, dendrimers, magnetic nanovectors, graphene oxide nanostructures, stimuli-responsive nanoparticles, gene therapy, folic acid receptor targeting, gastrin-releasing peptide receptor targeting, fibroblast activation protein targeting, urokinase-type plasminogen activator receptor targeting, biotin receptor targeting and transferrin receptor targeting. This review also highlights oncolytic viruses as OSCC therapy candidates.

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS.

Depression is one of the most common mental diseases, which seriously affects patients' physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. STATEMENT OF SIGNIFICANCE: ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

Fabrication of stimuli-responsive nanoparticles for high-efficiency chlorantraniliprole delivery and smart control of Spodoptera frugiperda

A novel stimuli-responsive delivery system consisting of silicon-based material and environmental-friendly carboxymethyl chitosan (CMCS) coating was designed to enhance the distribution of chlorantraniliprole (Cap) in maize plants (Zea mays L.) against fall armyworm (Spodoptera frugiperda). Herein, Cap was loaded into mesoporous silica nanoparticles and coated with CMCS as a delivery system. The synthesized Cap-loaded nanoparticles had a particle size of about 35 nm with good Cap loading efficiency and sustained-release properties. On the other hand, the delivery system could expand the distribution and duration of Cap in maize. Due to the difference in pH sensitivity of the nanocarrier, it improved the insecticidal activity of Cap against S. frugiperda and showed good biocompatibility for zebrafish (Danio rerio). Briefly, this new strategy for protecting maize plants not only meets the needs of the pest management markets, but also facilitates the utilization of agrochemical.

A Dual Protective Drug Delivery System Based on Lipid Coated Core-Shell Mesoporous Silica for Efficient Delivery of Cabazitaxel to Prostate Cancer Cells

Abstract Many advancements are happening in drug delivery to develop an excellent nanocarrier to deliver drugs to target sites bypassing clinical barriers, thereby improving cellular uptake. Lipid coating on mesoporous silica nanoparticles (MSNs) has significantly reduced the drawbacks of many MSNs and increased their compatibility. This study reports a dual protective acid stimuli-responsive lipid-coated core-shell mesoporous silica nanoparticle (CSMS) conjugated with cabazitaxel showing better drug release, cell uptake, and cytotoxicity, and suitability in the prostate cancer (PC-3) cell line. Initially, monodispersed CSMS were conjugated with cabazitaxel (CBZ) through a hydrazone linker (CBZ@Hy-CSMS), proving its appropriate use in designing a stimuli-responsive system. In the second part, CBZ-conjugated CSMS was coated with a lipid layer (L-CBZ@Hy-CSMS) by the liposome fusion method. The presented dual protective CSMS system showed a significant increase in drug delivery at pH 5.4 compared to 7.4, with a drastic decrease in premature drug release when exposed to pH 7.4. The lipid-coated CSMS showed excellent biocompatibility and better cellular uptake with enhanced cell cytotoxicity in PC-3 cancer cells as compared to the uncoated CSMS. CSMS with a lipid coating combined with a stimuli-responsive system could improve the therapeutic delivery and treatment difficulties in many other cell lines and diseases.

Actively targeted delivery of tamoxifen through stimuli-responsive polymeric nanoparticles for cancer chemotherapy

Actively targeted delivery of tamoxifen through stimuli-responsive polymeric nanoparticles for cancer chemotherapy

Effect of nanoparticle size on their distribution and retention in chronic inflammation sites

Nanomedicines are increasingly researched and used for the treatment of chronic inflammatory diseases. Herein, the effect of the size of nanoparticles on their distribution and retention in chronic inflammatory sites, as compared to healthy tissues, was studied in a mouse model with chronic inflammation in one of the hind footpads. Using PEGylated gold nanoparticles of 2, 10, 100, and 200 nm, we found that although the smaller nanoparticles of 2 and 10 nm showed greater distribution and slower clearance in the inflamed footpad than the relatively larger nanoparticles of 100 and 200 nm, the larger nanoparticles of 100 and 200 nm were more selectively distributed in the inflamed hind footpad than in the healthy hind footpad in the same mouse. Based on these findings, we prepared protein nanoparticles of 100–200 nm with albumin, IgG antibody, or anti-TNF-α monoclonal antibody (mAb). The nanoparticles can release proteins in response to high redox activity and/or low pH, conditions seen in chronic inflammation sites. We then showed that upon intravenous injection, those stimuli-responsive protein nanoparticles distributed more selectively in the inflamed footpad than free proteins and remained longer in the inflamed footpad than similar protein nanoparticles that are not sensitive to high redox activity or low pH. These findings support the feasibility of increasing the selectivity of nanomedicines and protein therapeutics to chronic inflammation sites and prolonging their retention at the sites by innovative nanoparticle engineering.Graphical

Enhanced fungicidal activity and mechanism of pyraclostrobin nanoparticle with reactive oxygen species responsiveness against Rhizoctonia solani

The frequent application of pesticides has caused adverse effects on humans and the environment. Stimuli-responsive nanoparticles can enhance the control efficacy of pesticides to pest insects or fungus and reduce impacts on non-target organisms. In the present work, 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) groups were conjugated onto β-cyclodextrin (β-CD) to form a H2O2-eliminating material (Ox-bCD), and then the nanoparticiles (PYR@OxbCD) loaded pyraclostrobin (PYR) were successfully fabricated by a nanoprecipitation. The prepared PYR@OxbCD had excellent reactive oxygen species (ROS) release dependency, and significantly enhanced fungicidal activity against Rhizoctonia solani in vitro. PYR@OxbCD could accurately release PYR at infected rice plants, providing a better control efficacy than PYR suspension concentrate (SC). The contact angle of PYR@OxbCD on leaves was reduced, and the spreading and antiphotolysis properties were increased, which may lead to an increase of deposition and a lower dissipation rate. Furthermore, the released PYR from PYR@OxbCD enhanced the activity of peroxidase (POD) and catalase (CAT), and up-regulated the expression of defense genes including PAL, PR10, CHI, CAT, GluPOD and AsPOD. PYR@OxbCD exhibited a much weaker effect on microbial abundance in rice cropping systems. The study provides an idea for smart delivery of fungicides to prevent plant pathogens and offers a more comprehensive view about the resistance of R. solani-infected rice triggered by PYR@OxbCD in levels of phenotype, enzymatic activity, gene expression, and microbiome.

Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies

Currently, commercially available antibody therapies must be delivered via parenteral administration. Oral delivery of antibodies could increase patient compliance and improve quality of life, however there is currently no viable system for delivering antibodies orally. In this work, a self-assembled, pH-responsive nanoparticle delivery system was developed to load and deliver antibodies via the oral route. The nanoparticles were synthesized via nanoprecipitation using the pH-responsive copolymers based on poly(methacrylic acid-co-methyl methacrylate)-block-poly(ethylene glycol). The reversibly hydrophobic nature of this polymer allowed it to function as an antibody delivery system via self-assembly. Characteristics of the polymer, including monomer ratios and molecular weight, as well as parameters of the nanoprecipitation process were optimized using Design of Experiments to achieve nanoparticles with desired size, polydispersity, loading efficiency, and release characteristics. Ultimately, the synthesized and optimized nanoparticles exhibited a hydrodynamic size within a range that avoids premature clearance, a low polydispersity index, and high IgG loading efficiency. In in vitro antibody release studies at physiologically relevant pH values, the nanoparticles exhibit promising release profiles. The nanoparticles presented in this work show potential as oral delivery vehicles for therapeutic antibodies.