Use Of Delivery Systems Research Articles

Effect of starch molecular weight on the colon-targeting delivery and promoting GLP-1 secretion of starch-lecithin complex nanoparticles

β-lactoglobulin (β-LG) could stimulate enteroendocrine L cells which are located in the colon to secrete glucagon-like peptide-1 (GLP-1) to maintain glycemic homeostasis. In order to ensure that β-LG can intactly arrive in the colon through oral administration, colon-targeting delivery systems should be engineered. In this study, β-LG encapsulated nanoparticles were fabricated through molecular interaction and self-assembly using octenyl succinic anhydride (OSA) modified potato starch-lecithin complex (OPC) with different starch molecular weight (Mw). OPC with lower starch Mw exhibited stronger interaction with β-LG and its correspondent nanoparticles showed smaller diameter and higher structural compactness. Obtained OPC based nanoparticles were spherical, of Z-average diameter from 139.9 nm to 246.8 nm, of zeta-potential from −1.94 mV to −9.42 mV and of α value from 1.41 to 2.14. Additionally, OPC based nanoparticles with lower starch Mw exhibited excellent capacity for maintaining structure integrality in simulated upper gastrointestinal tract (GIT) environment. Optimized OPC based nanoparticles with 224.4 nm of diameter, −9.00 mV of zeta-potential and 2.14 of α value had well mucus-penetrating capacity (59.25%) and colon-targeting capacity (49.18% released in simulated colonic fluid). Moreover, the OPC based nanoparticles passed through the upper GIT signally stimulated GLP-1 secretion (improved 119.23%) primarily through β-LG targeting released in colon in the prophase and short-chain fatty acids and reducing sugar produced by colonic microbial degradation of OPC in the later phase. Altogether, OPC based nanoparticles have great potential of mucus penetrating and colon-targeting delivery systems for use in stimulating GLP-1 secretion which can support applications for maintaining glycemic homeostasis.

Modifying a mini drone for remote drug delivery for wildlife medicine

Remote drug delivery is an essential tool for administering medication to wildlife. However, the conventional method, the dart gun, has limitations in terms of injection distance, posing risks for operators. This study aimed to modify a mini drone equipped with a dart syringe and delivery system for use with large wildlife. A commercial mini drone was modified to release a syringe dart using a vertical gravity-based delivery system. The performance of the drone and delivery system was evaluated based on accuracy to the target and penetration ability through pig skin. The evaluation compared a dart with or without a plastic shell, with tests conducted both indoors and outdoors. The results indicated that the higher the drone's flight, the more the dart tended to deviate from the target. In outdoor tests, a syringe dart without a shell showed greater accuracy than a dart with a shell. Regarding penetration ability, only a dart without a shell had a 100% success rate at a maximum height of 5 metres, with an overall statistical difference (P = 0.01). In conclusion, this study represents the first scientific validation of using mini drones for remote drug injections that could be used in large wildlife medicine.

Placental Drug Delivery to Treat Pre-Eclampsia and Fetal Growth Restriction.

Pre-eclampsia and fetal growth restriction (FGR) continue to cause unacceptably high levels of morbidity and mortality, despite significant pharmaceutical and technological advances in other disease areas. The recent pandemic has also impacted obstetric care, as COVID-19 infection increases the risk of poor pregnancy outcomes. This review explores the reasons why it lacks effective drug treatments for the placental dysfunction that underlies many common obstetric conditions and describes how nanomedicines and targeted drug delivery approaches may provide the solution to the current drug drought. The ever-increasing range of biocompatible nanoparticle formulations available is now making it possible to selectively deliver drugs to uterine and placental tissues and dramatically limit fetal drug transfer. Formulations that are refractory to placental uptake offer the possibility of retaining drugs within the maternal circulation, allowing pregnant individuals to take medicines previously considered too harmful to the developing baby. Liposomes, ionizable lipid nanoparticles, polymeric nanoparticles, and adenoviral vectors have all been used to create efficacious drug delivery systems for use in pregnancy, although each approach offers distinct advantages and limitations. It is imperative that recent advances continue to be built upon and that there is an overdue investment of intellectual and financial capital in this field.

Evaluation of a Novel Dry Powder Surfactant Aerosol Delivery System for Use in Premature Infants Supported with Bubble CPAP.

Aerosolized lung surfactant therapy during nasal continuous positive airway pressure (CPAP) support avoids intubation but is highly complex, with reported poor nebulizer efficiency and low pulmonary deposition. The study objective was to evaluate particle size, operational compatibility, and drug delivery efficiency with various nasal CPAP interfaces and gas humidity levels of a synthetic dry powder (DP) surfactant aerosol delivered by a low-flow aerosol chamber (LFAC) inhaler combined with bubble nasal CPAP (bCPAP). A particle impactor characterized DP surfactant aerosol particle size. Lung pressures and volumes were measured in a preterm infant nasal airway and lung model using LFAC flow injection into the bCPAP system with different nasal prongs. The LFAC was combined with bCPAP and a non-heated passover humidifier. DP surfactant mass deposition within the nasal airway and lung was quantified for different interfaces. Finally, surfactant aerosol therapy was investigated using select interfaces and bCPAP gas humidification by active heating. Surfactant aerosol particle size was 3.68 µm. Lung pressures and volumes were within an acceptable range for lung protection with LFAC actuation and bCPAP. Aerosol delivery of DP surfactant resulted in variable nasal airway (0-20%) and lung (0-40%) deposition. DP lung surfactant aerosols agglomerated in the prongs and nasal airways with significant reductions in lung delivery during active humidification of bCPAP gas. Our findings show high-efficiency delivery of small, synthetic DP surfactant particles without increasing the potential risk for lung injury during concurrent aerosol delivery and bCPAP with passive humidification. Specialized prongs adapted to minimize extrapulmonary aerosol losses and nasal deposition showed the greatest lung deposition. The use of heated, humidified bCPAP gases compromised drug delivery and safety. Safety and efficacy of DP aerosol delivery in preterm infants supported with bCPAP requires more research.

Polymicellar-based drug delivery systems for use in nanodentistry

Polymicellar-based drug delivery systems for use in nanodentistry

Novel Polymeric Nanomaterial Based on Poly(Hydroxyethyl Methacrylate-Methacryloylamidophenylalanine) for Hypertension Treatment: Properties and Drug Release Characteristics.

In this study, a novel polymeric nanomaterial was synthesized and characterized, and it its potential usability in hypertension treatment was demonstrated. For these purposes, a poly(hydroxyethyl methacrylate-methacryloylamidophenylalanine)-based polymeric nanomaterial (p(HEMPA)) was synthesized using a mini-emulsion polymerization technique. The nanomaterials were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and zeta size analysis. The synthesized p(HEMPA) nanomaterial had a diameter of about 113 nm. Amlodipine-binding studies were optimized by changing the reaction conditions. Under optimum conditions, amlodipine's maximum adsorption value (Qmax) of the p(HEMPA) nanopolymer was found to be 145.8 mg/g. In vitro controlled drug release rates of amlodipine, bound to the nanopolymer at the optimum conditions, were studied with the dialysis method in a simulated gastrointestinal system with pH values of 1.2, 6.8 and 7.4. It was found that 99.5% of amlodipine loaded on the nanomaterial was released at pH 7.4 and 72 h. Even after 72 h, no difference was observed in the release of AML. It can be said that the synthesized nanomaterial is suitable for oral amlodipine release. In conclusion, the synthesized nanomaterial was studied for the first time in the literature as a drug delivery system for use in the treatment of hypertension. In addition, AML-p(HEMPA) nanomaterials may enable less frequent drug uptake, have higher bioavailability, and allow for prolonged release with minimal side effects.

Advances in Nanofabrication Technology for Nutraceuticals: New Insights and Future Trends.

Bioactive components such as polyphenolics, flavonoids, bioactive peptides, pigments, and essential fatty acids were known to ward off some deadliest diseases. Nutraceuticals are those beneficial compounds that may be food or part of food that has come up with medical or health benefits. Nanoencapsulation and nanofabricated delivery systems are an imminent approach in the field of food sciences. The sustainable fabrication of nutraceuticals and biocompatible active components indisputably enhances the food grade and promotes good health. Nanofabricated delivery systems include carbohydrates-based, lipids (solid and liquid), and proteins-based delivery systems. Solid nano-delivery systems include lipid nanoparticles. Liquid nano-delivery systems include nanoliposomes and nanoemulsions. Physicochemical properties of nanoparticles such as size, charge, hydrophobicity, and targeting molecules affect the absorption, distribution, metabolism, and excretion of nano delivery systems. Advance research in toxicity studies is necessary to ensure the safety of the nanofabricated delivery systems, as the safety of nano delivery systems for use in food applications is unknown. Therefore, improved nanotechnology could play a pivotal role in developing functional foods, a contemporary concept assuring the consumers to provide programmed, high-priced, and high-quality research toward nanofabricated delivery systems.

"Guide" of muscone modification enhanced brain-targeting efficacy and anti-glioma effect of lactoferrin modified DTX liposomes.

Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over-expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a "guide" drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain-targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual-modified liposomes cross blood-brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual-modified liposomes (Lf-LP-Mu-DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf-LP-Mu-DTX increased uptake in both U87-MG cells and hCMEC/D3 cells, enhanced penetration of U87-MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti-tumor effects. In conclusion, "guide" of muscone modification enhanced brain-targeting efficacy of Lf modified liposomes, Lf and muscone dual-modified docetaxel loaded liposomes present a potential brain-targeting drug delivery system for use in the future treatment of gliomas.

Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells.

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The β-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the β-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the β-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.

A novel multifunctional NCQDs-based injectable self-crosslinking and in situ forming hydrogel as an innovative stimuli responsive smart drug delivery system for cancer therapy

In this work, we offer an easy approach to develop a novel injectable, pH sensitive and in situ smart drug delivery system for use in cancer treatments. The developed hydrogels containing nitrogen doped carbon quantum dots (NCQD), doxorubicin (Dox) and hydroxyapatite (HA) were obtained by in situ self-crosslinking. Characterization of the synthesized nanomaterials, interactions between NCQD/Dox/HA hydrogel structure were carried out by TEM, FESEM, EDS, FTIR, XPS, XRD, Zeta potential, DLS, UV–Vis, SEM, gelation time, injectability and DIST measurements. In addition, antibacterial evaluation which was performed against Staphylococcus aureus realized that HA compound significantly increased the antibacterial activity of the hybrid hydrogel. The anticancer drug release to the tumor cell microenvironment with a pH of 5.5 was found to be higher compared to the release in the normal physiological range of pH 6.5 and 7.4. MTT and live/dead assays were also performed using L929 fibroblastic cell lines to investigate the cytotoxic behavior of NCQDs, and NCQDs/Dox/HA hydrogels. Furthermore, the NCQDs/Dox/HA hydrogel could transport Dox within a MCF-7 cancerous cell at specifically acidic pH. Additionally, imaging of cell line was observed using NCQDs and their use in imaging applications and multicolor features in the living cell system were evaluated. The overall study showed that in situ formed NCQDs/Dox/HA hydrogel represented a novel and multifunctional smart injectable controlled-release drug delivery system with great potential, which may be considered as an attractive minimal invasive smart material for future intelligent delivery of chemotherapeutic drug and disease therapy applications.

Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and is associated with a very poor prognosis. The standard treatment for newly diagnosed patients involves total tumor surgical resection (if possible), plus irradiation and adjuvant chemotherapy. Despite treatment, the prognosis is still poor, and the tumor often recurs within two centimeters of the original tumor. A promising approach to improving the efficacy of GBM therapeutics is to utilize biomaterials to deliver them locally at the tumor site. Local delivery to GBM offers several advantages over systemic administration, such as bypassing the blood-brain barrier and increasing the bioavailability of the therapeutic at the tumor site without causing systemic toxicity. Local delivery may also combat tumor recurrence by maintaining sufficient drug concentrations at and surrounding the original tumor area. Herein, we critically appraised the literature on local delivery systems based within the following categories: polymer-based implantable devices, polymeric injectable systems, and hydrogel drug delivery systems. We also discussed the negative effect of hypoxia on treatment strategies and how one might utilize local implantation of oxygen-generating biomaterials as an adjuvant to enhance current therapeutic strategies.

Physicochemical Characterization of PHBV Nanoparticles Functionalized with Multiple Bioactives Designed to be Theranostics for Lung Cancer

Lung cancer is a neoplasm associated with bacterial infections, main reason, to design a combined chemotherapy and antimicrobial treatment. Due to adverse drug reactions, we designed and synthetized polymer Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles loaded with clarithromycin and paclitaxel and Superparamagnetic Iron Oxide Nanoparticles (SPION). Spherical nanoparticles with diameters ranging between 176 ± 19 and 222 ± 68 nm, hydrophilic and had a net negative surface charge were obtained. These nanoparticles can be lyophilized and resuspended in polar environments without affecting their physicochemical characteristics and maintaining their antibacterial activity. Both drugs interacted differently with the polymer, avoiding competition between them and facilitating the simultaneous encapsulation. The paclitaxel loaded in these nanoparticles remains almost completely encapsulated during the first 24 h under physiological conditions, allowing its accumulation and release in sites of high permeability and retention, such as tumors. In summary, these PHBV nanoparticles loaded with clarithromycin, paclitaxel and SPION are a promising drug delivery system for use in theranostics against lung cancer.

Development of antibacterial nanoemulsions incorporating thyme oil: Layer-by-layer self-assembly of whey protein isolate and chitosan hydrochloride

The aim of this study was to develop a thyme oil emulsion with good physicochemical properties and antibacterial activity. Initially, oil-in-water emulsions containing whey protein-coated essential oil droplets were prepared by high-pressure homogenization. The double-layer emulsions were formed around the oil droplets by electrostatic deposition of cationic chitosan hydrochloride onto the anionic protein-coated droplets. Then, the structure, physicochemical properties, and storage stability of the emulsions were determined. Emulsions formulated using 1% v/v thyme oil, 0.7 wt% whey protein, and 0.25 wt% of chitosan hydrochloride contained relatively small cationic droplets. Moreover, the emulsions containing double-layer coatings were shear-thinning fluids. Storage tests indicated that double-layer emulsions had better stability than the single-layer. Antibacterial tests indicated that the double-layer emulsions exhibited prolonged antibacterial activity against two model food pathogens: E. coli and S. aureus. These results provide a scientific basis for the rational design of antimicrobial delivery systems for use in foods.

Spray Characterization of Aerosol Delivery Systems for Use in Stored Product Facilities

HighlightsHandheld sprayers generated larger droplets and wider droplet size distributions than compressed gas sprayers.Sprayers with higher pressure and nozzles with wider spray angle produced smaller droplets.Droplet size distribution influenced spray coverage, mass concentration, deposition, and sprayer efficacy.The handheld sprayers had less spray coverage and efficiency than the compressed gas sprayers.The deposition at different locations was influenced by the volume of the space, aerosol dosage, and spray time.Abstract. Aerosol insecticides, including pyrethrins, can be used as methyl bromide replacements to control stored product insects inside flour mills and rice mills. The effectiveness of aerosol application for insect control requires knowing the spray characteristics of the equipment to be used and understanding factors that influence the effectiveness of insecticide application. The objectives of this study, as part of efforts to optimize aerosol applications, were to evaluate the characteristics of six aerosol delivery systems (two handheld sprayers and compressed gas sprayer systems fitted with two types of manifolds and two types of nozzles), estimate the dispersion and deposition of aerosol in a simulated stored product facility, and determine how the dispersion and deposition are affected by the characteristics of the sprayers. Results showed that the spray systems differed significantly in spray characteristics. The compressed gas sprayers generated significantly smaller droplets, more uniform droplet size distribution, and better spray coverage than the handheld sprayers. The ellipsoidal nozzle produced significantly smaller droplets than the circular nozzle. While the type of manifold had no significant effect on deposition, higher aerosol dosage and spray time resulted in significantly higher deposition. Results of this study will be used to improve spray techniques for stored product insect control, to validate computational fluid dynamics modeling of aerosol application, and to improve testing methods in large-scale spray testing inside commercial facilities. Keywords: APS spectrometer, Droplet size distribution, HELOS KR-Vario, Mass deposition, Spray characteristics, Spray nozzles.

Recognition Sites for Cancer-targeting Drug Delivery Systems.

Target-homing drug delivery systems are now gaining significant attention for use as novel therapeutic approaches in antitumor targeting for cancer therapy. Numerous targeted drug delivery systems have been designed to improve the targeting effects because these systems can display a range of favorable properties, thus, providing suitable characteristics for clinical applicability of anticancer drugs, such as increasing the solubility, and improving the drug distribution at target sites. The majority of these targeting systems are designed with respect to differences between cancerous and normal tissues, for instance, the low pH of tumor tissues or overexpressed receptors on tumor cell membranes. Due to the growing number of targeting possibilities, it is important to know the tumor-specific recognition strategies for designing novel, targeted, drug delivery systems. Herein, we identify and summarize literature pertaining to various recognition sites for optimizing the design of targeted drug delivery systems to augment current chemotherapeutic approaches. This review focuses on the identification of the recognition sites for developing targeted drug delivery systems for use in cancer therapeutics. We have reviewed and compiled cancer-specific recognition sites and their abnormal characteristics within tumor tissues (low pH, high glutathione, targetable receptors, etc.), tumor cells (receptor overexpression or tumor cell membrane changes) and tumor cell organelles (nuclear and endoplasmic reticular dysregulation) utilizing existing scientific literature. Moreover, we have highlighted the design of some targeted drug delivery systems that can be used as homing tools for these recognition sites. Targeted drug delivery systems are a promising therapeutic approach for tumor chemotherapy. Additional research focused on finding novel recognition sites, and subsequent development of targeting moieties for use with drug delivery systems will aid in the evaluation and clinical application of new and improved chemotherapeutics.

Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus.

Highly active antiretroviral therapy (HAART) can turn human immunodeficiency virus-1 (HIV-1) infection into a controllable chronic disease, but because of the presence of an HIV reservoir, it cannot completely eliminate the virus in HIV-infected patients. The activation of latent reservoirs is the key to the successful treatment of acquired immune deficiency syndrome (AIDS). As a class of latency-reversing agents (LRAs), histone deacetylase inhibitors (HDACis), such as panobinostat, have been the most widely investigated, but most of them have resulted in only a modest and transient activation of HIV latency. To improve the potency of latency activation, an injectable peptide self-assembly nanoparticle loaded with panobinostat (PNP-P) was designed with the ability to efficiently penetrate the cell to achieve better drug delivery and activation of latent HIV. The results confirmed that these nanoparticles could activate latently infected cells in vitro and in vivo and activate peripheral blood mononuclear cells (PBMCs) from latently infected patients ex vivo. Increased cellular drug uptake made the PNP-P more effective than panobinostat alone. Therefore, this strategy demonstrates that nanotechnology can help improve the activation of latent HIV, and this study lays a foundation for further development of LRA delivery systems for use against an HIV reservoir.

Architectures and Mechanical Properties of Drugs and Complexes of Surface-Active Compounds at Air-Water and Oil-Water Interfaces.

Drugs can represent a multitude of compounds from proteins and peptides, such as growth hormones and insulin and on to simple organic molecules such as flurbiprofen, ibuprofen and lidocaine. Given the chemical nature of these compounds two features are always present. A portion or portions of the molecule that has little affinity for apolar surfaces and media and on the contrary a series of part or one large part that has considerable affinity for hydrophilic, polar or charged media and surfaces. A series of techniques are routinely used to probe the molecular interactions that can arise between components, such as the drug, a range of surface- active excipients and flavor compounds, for example terpenoids and the solvent or dispersion medium. Fifty-eight papers were included in the review, a large number (16) being of theoretical nature and an equally large number (14) directly pertaining to medicine and pharmacy; alongside experimental data and phenomenological modelling. The review therefore simultaneously represents an amalgam of review article and research paper with routinely used or established (10) and well-reported methodologies (also included in the citations within the review). Experimental data included from various sources as diverse as foam micro-conductivity, interferometric measurements of surface adsorbates and laser fluorescence spectroscopy (FRAP) are used to indicate the complexity and utility of foams and surface soft matter structures for a range of purposes but specifically, here for encapsulation and incorporation of therapeutics actives (pharmaceutical molecules, vaccines and excipients used in medicaments). Techniques such as interfacial tensiometry, interfacial rheology (viscosity, elasticity and visco-elasticity) and nanoparticle particle size (hydrodynamic diameter) and charge measurements (zeta potential), in addition to atomic force and scanning electron microscopy have proven to be very useful in understanding how such elemental components combine, link or replace one another (competitive displacement). They have also proven to be both beneficial and worthwhile in the sense of quantifying the unseen actions and interplay of adsorbed molecules and the macroscopic effects, such as froth formation, creaming or sedimentation that can occur as a result of these interactions. The disclosures and evaluations presented in this review confirm the importance of a theoretical understanding of a complex model of the molecular interactions, network and present a framework for the understanding of really very complex physical forms. Future therapeutic developers rely on an understanding of such complexity to garner a route to a more successful administration and formulation of a new generation of therapeutic delivery systems for use in medicine.

Opportunities and challenges for intranasal oxytocin treatment studies in nonhuman primates.

Nonhuman primates provide a human-relevant experimental model system to explore the mechanisms by which oxytocin (OT) regulates social processing and inform its clinical applications. Here, we highlight contributions of the nonhuman primate model to our understanding of OT treatment and address unique challenges in administering OT to awake behaving primates. Prior preclinical research utilizing macaque monkeys has demonstrated that OT can modulate perception of other individuals and their expressions, attention to others, imitation, vigilance to social threats, and prosocial decisions. We further describe ongoing efforts to develop an OT delivery system for use in experimentally naïve juvenile macaque monkeys compatible with naturalistic social behavior outcomes. Finally, we discuss future directions to further develop the rhesus monkey as a preclinical test bed to evaluate the effects of OT exposure and advance efforts to translate basic science OT research into safe and effective OT therapies.

Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles.

Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.

Reducible disulfide poly(beta-amino ester) hydrogels for antioxidant delivery

Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses. Upon introduction into a reducing environment, these disulfide-containing hydrogels cleave to present bound-thiol groups, yet remain in the bulk form at up to 66 mol% cystamine of the total amines. By controlling the molar fraction of cystamine, it was apparent that the thiol content varied human umbilical vein endothelial cell (HUVEC) viability IC50 values across an order of magnitude. Further, upon introduction of an enzymatic oxidative stress generator to the cell culture (HX/XO), pre-incubated thiolated hydrogel degradation products conferred cellular and mitochondrial protection from acute oxidative stress, whereas non-reduced disulfide-containing degradation products offered no protection. This polymer may be an advantageous implantable drug delivery system for use in acute oxidative stress prophylaxis and/or chronic oxidative stress cell therapies due to its solid/liquid reversibility in a redox environment, controlled thiolation, high loading capacity through covalent drug-addition, and simple post-synthesis modification which bound-thiols introduce. Statement of SignificanceIn this work, we demonstrate a unique property of disulfide containing degradable biomaterials. By changing the redox state of the degradation products (from oxidized to reduced), it is possible to increase the IC50 of the material by an order of magnitude. This dramatic shift is linked directly to the oxidative stress response of the cells and suggests a possible mechanism by which one can tune the cellular response to degradable biomaterials.