Release Of Heparin Research Articles

Multiple Drug Delivery from Mesoporous Coating Realizing Combination Therapy for Bare Metal Stents

The simultaneous loading of multifunctional drugs has been regarded as one of the major challenges in the drug delivery system. Herein, a mesoporous silica coating was constructed on a bare metal stent surface by an evaporation-induced self-assembly method, in which both hydrophilic and hydrophobic drugs (heparin and rapamycin) were encapsulated by a one-pot method for the first time, and the release behaviors of these drugs were studied. The releasing mechanisms of these drugs were investigated in detail. Rapid release of heparin can achieve anticoagulation and endothelialization, whereas slow release of rapamycin can realize antiproliferative therapy for long term. In vitro hemocompatibility and promotion for proliferation of vein endothelial cells and the inhibition of smooth muscle cells were conducted. In vivo stent implantation results verify that the mesoporous silica coating with both heparin and rapamycin can successfully accelerate the endothelialization process and realize the antiproliferative therapy for as long as 3 months. These results indicate that this multifunctional mesoporous coating containing both hydrophilic and hydrophobic drugs might be a promising stent coating in the future.

Chitosan-heparin nanoparticle coating on anodized NiTi for improvement of blood compatibility and biocompatibility.

The aim of this study was to simultaneously improve blood compatibility and corrosion resistance of nitinol via two-step process; anodizing and consequently coating with chitosans-heparin nanoparticles. Moreover, the role of these surface modification processes on the heparin release kinetic and blood compatibility was investigated. Finally, the interaction between human umbilical vein endothelial cells (HUVECs) and surface modified samples was investigated. Electrochemical characterization revealed that while Ni ions released from the anodized sample (9 ppb), chitosan-heparin nanoparticle coatings prohibited from Ni ion release form NiTi substrate. Moreover, the controlled release of heparin was found from chitosan-heparin nanoparticle coating deposited on the nanotubes, leading to significant improvement of blood compatibility. Finally, HUVECs were attached and proliferated on the chitosan-heparin nanoparticle coated samples confirming the cell compatibility of samples. In summary, results proved that two-step anodizing process and heparin release could promote both endothelial cell compatibility and blood compatibility to nitinol surface which might be appropriate for coronary stent application.

Immunological response to bacterial infection in a pelagic tunicate: Inflammation in the salp Thalia democratica

Thaliaceans are pelagic tunicates that play a key role in trophic chains of the oceans. In the field of tunicate immunity, a notable gap is the lack of data on their inflammatory response. The common salp, Thalia democratica, possesses scant immunocytes, represented by a phagocytic line (hyaline amebocytes) and a mast cell-like line (granular cells). We aimed to provide the first investigation of defense reactions upon exposure to a large amount of bacteria (Bacillus clausii). We detected (i) bacterial phagocytosis by hyaline amebocytes, (ii) degradation of phagocytizing hyaline amebocytes in the tunic after transcellular diapedesis from the hemocoel, and (iii) release of heparin, histamine, and TNF-α by granular cells. Cell degranulation and phagocytosis occurred in epidermal cells lining the hemocoel, and an excess of mucus was observed in the post-branchial gut, causing a functional inhibition of cilia and microvilli. These findings indicate multi-step events comparable to an inflammation involving responses at both tissue and organismal levels.

Preparation and characterization of functionalized heparin-loaded poly-Ɛ-caprolactone fibrous mats to prevent infection with human papillomaviruses.

In this study, heparin-loaded poly-ɛ-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was obtained via heparin crosslinking. This was achieved by running a carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction on preformed PCL fibers. In vitro HPV16 L1 protein binding capacity studies were performed. Infectivity assays were done using HPV16 pseudoviruses (PsVs) carrying a GFP plasmid to directly test the ability of the fibrous mats to prevent internalization of HPV PsVs. The crosslinked heparin material presented a dissociation constant (Kd) value comparable to those found in the literature for different heparin-protein L1 peptide interactions. Both materials significantly reduced internalization of HPV PsVs, with a reduction of 94% of PsVs internalization when matrix encapsulated heparin-loaded material was present. Differences in performance between the two proposed structures are discussed.

Crosslinked gelatin hydrogels as carriers for controlled heparin release

The application of heparin as anticoagulant, anti-inflammatory and growth factor regulating agent is currently limited by its narrow therapeutic window. Here, we describe the use of chemically crosslinked gelatin hydrogels as delivery platform to achieve the control of heparin release over time. Different hydrogel formulations and two strategies for heparin loading were tested. The synergic electrostatic interactions between heparin and gelatin hydrogels resulted in a sustained release until 60 h, demonstrated by toluidine blue tests. Platelets adhesion was significantly reduced in heparin-loaded hydrogels, thus proving good heparin bioactivity after processing. Our heparin-loaded hydrogels represent a possible valid option to develop coating for catheters and cardiovascular devices, or skin dressings.

A Method for Preparation of an Internal Layer of Artificial Vascular Graft Co-Modified with Salvianolic Acid B and Heparin.

Studies have shown that salvianolic acid B (SAB), which is derived from Chinese salvia ( Salvia miltiorrhiza), a plant used in traditional Chinese medicine, can promote the proliferation and migration of endothelial cells. The inner layer of an artificial vascular graft was fabricated using the coaxial electrospinning method and was loaded with the anticoagulant heparin and SAB. The release of heparin and SAB was sustained for almost 30 days and without an initial burst release of SAB. Furthermore, the combined effect of SAB and heparin contributed to promoting human umbilical vein endothelial cell (HUVEC) growth and improved the blood compatibility of the graft. In addition, upregulation of GRP78 by SAB protected human endothelial cells from oxidative stress-induced cellular damage. In vivo evaluation through Masson's trichrome and H&E staining was performed after the graft was subcutaneously embedded in SD rats for 2 weeks and indicated that the graft possessed satisfactory biocompatibility and did not cause a significant immune response. Hence, the functional inner layer is promising for preventing acute thrombosis and promotes rapid endothelialization of artificial vascular grafts.

Hemocompatible and Bioactive Heparin-Loaded PCL-α-TCP Fibrous Membranes for Bone Tissue Engineering.

The combination of bioactive components such as calcium phosphates and fibrous structures are encouraging niche-mimetic keys for restoring bone defects. However, the importance of hemocompatibility of the membranes is widely ignored. Heparin-loaded nanocomposite poly(ε-caprolactone) (PCL)-α-tricalcium phosphate (α-TCP) fibrous membranes are developed to provide bioactive and hemocompatible constructs for bone tissue engineering. Nanocomposite membranes are optimized based on bioactivity, mechanical properties, and cell interaction. Consequently, various concentrations of heparin molecules are loaded within nanocomposite fibrous membranes. In vitro heparin release profiles reveal a sustained release of heparin over the period of 14 days without an initial burst. Moreover, heparin encapsulation enhances mesenchymal stem cell (MSC) attachment and proliferation, depending on the heparin content. It is concluded that the incorporation of heparin within TCP-PCL fibrous membranes provides the most effective cellular interactions through synergistic physical and chemical cues.

Preparation and Properties of Janus Heparin-Loaded Ammoniated-Hollow Mesoporous Silica Nanomotors

In this case, the development of Janus heparin-loaded ammoniated-hollow mesoporous silica (H-A-HMS) nanomotors was reported. First, A-HMS nanoparticles were prepared by combination of hard template (Fe3O4 regarded as core), soft template (cetyltrimethylammonium bromide (CTAB) regarded as mesoporous template agent) and ammoniated process. Then, the heparin was loaded into A-HMS nanoparticles by a simple soaking process, and Janus H-A-HMS nanomotors were fabricated by platinum (Pt) decorating onto the partial surface of H-A-HMS nanoparticles, which the bubble-propelled motion was obtain by the help of Pt catalytic decomposition of hydrogen peroxide (H2O2) into oxygen (gas) and water. Finally, results of a performance test indicated that the H-A-HMS nanomotors we proposed had good blood compatibility, noncytotoxicity, high load and controlled release of heparin, and autonomous motion ability. They will bring great potential for more applications of heparin in the biomedical field.

Incorporation of ZnO nanoparticles into heparinised polyvinyl alcohol/chitosan hydrogels for wound dressing application

Available wound dressings have some major deficiencies including low water vapor transmission rate (WVTR), low absorption of wound fluids, and not providing a suitable and moist environment for wound healing. The main advantage of hydrogels is giving aid to the creation of a moist and cool environment for wound healing and providing high water vapor permeability along with preventing penetration of microbes into the wound surface. Therefore, hydrogels of heparinized polyvinyl alcohol (PVA)/chitosan (CS)/nano zinc oxide (nZnO) were prepared to be used as wound dressing. Samples were characterized via infrared spectrometry (FTIR), X-ray diffraction (XRD) and scanning electron microscope (SEM). In addition, other properties including swelling ratio, water vapor transmission rate, the size of pores, mechanical and thermal properties, cell viability, and antibacterial efficiency were investigated. Water vapor permeability, porosity, and swelling ratio showed a wide range of numerical values that facilitate the use of provided samples as ideal wound dressings. Besides, investigating mechanical and thermal properties exhibited the improvement of mentioned properties by adding nano zinc oxide. Furthermore, Heparin loading was conducted on optimum samples. Heparin release rate decreased and was more sustained by adding nanoparticles compared to hydrogel wound dressings without nZnO. Cell viability of bionanocomposite samples showed no toxicity after loading nanoparticles and this value was >70% for all samples. Antibacterial properties of hydrogel samples can effectively protect wounds especially with an increase nZnO content. Hence, these hydrogels were found applicable as robust wound dressings.

Electrolytic deposition of hydroxyapatite/calcium phosphate-heparin/gelatin-heparin tri-layer composites on NiTi alloy to enhance drug loading and prolong releasing for biomedical applications

Although the initial success of bare metal stents has significantly reduced the restenosis rate for percutaneous transluminal coronary angioplasty from 35% to 25%, the biological mechanism such as vascular smooth muscle cells (VSMCs) proliferation and neo-intimal hyperplasia still may induce in-stent restenosis (ISR). Therefore, some drug eluting stents have been introduced to reduce ISR. In this study, heparin (Hep) combined with calcium phosphate (CaP) and gelatin (Gel), without any additive or solvent, is co-deposited on hydroxyapatite (HA) coated NiTi alloy in order to enhance the drug load and the sustaining release for promoting the hemo-compatibility of NiTi substrate. Polarization tests were carried out in several solutions to investigate deposition mechanisms. Heparin contained composite coatings were characterized by X-ray diffractometry, Field emission scanning electron microscope, Fourier transform infrared spectroscopy, toluidine blue colorimetric assay, UV–visible spectrometer and kinetic clotting tests. The consequences indicate that heparin accompanied respectively with CaP, and Gel through ionic bonds can be loaded on the NiTi alloy. The porous post-HA coating can dramatically enhance the heparin content from 148 for the single layer coating (CaP-Hep) to 325 μg/cm2 for the tri-layer coating (HA/CaP-Hep/Gel-Hep), also resulting in the heparin release duration from 1 to >35 days, supposed to meet the requirement to prevent the proliferation of VSMCs. Both the drug content and releasing time are remarkable. As the result of clotting tests in vitro, drug loaded composite coatings reveal good anticoagulant property which is proportional to the cumulative content of drug release in an hour, indicating no denaturalization of heparin found during the electrochemical process.

Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures.

The surgical connection of blood vessels, anastomosis, is a critical procedure in many reparative, transplantation, and reconstructive surgical procedures. However, effective restoration of circulation is complicated by pathological clotting (thrombosis) or progressive occlusion due to excess cell proliferation that often leads to additional surgeries and increases morbidity and mortality risk for patients. Pharmaceutical agents have been tested to prevent these complications, but many have unacceptable systemic side effects. Therefore, an alternative approach to deliver these drugs at the site of injury in a controlled manner is necessary. The objective of this study was to develop electrospun nanofibers composed of polyester poly(lactide- co-glycolide) (PLGA), poly(ethylene oxide) (PEO), and positively charged copolymer, poly(lactide- co-glycolide)- graft-polyethylenimine (PgP) for electrostatic binding and release of heparin for application as an antithrombotic microvascular suture. PgP was synthesized with different coupling ratios between PLGA and branched polyethylenimine (bPEI) to obtain PgP1 (∼1 PLGA grafted to 1 bPEI) and PgP3.7 (∼3.7 PLGA grafted to 1 bPEI). Nanofiber yarns (PLGA/PEO/PgP1 and PLGA/PEO/PgP3.7) were fabricated by electrospinning. Heparin immobilization on the positively charged nanofiber yarns was visualized using fluorescein-conjugated heparin (F-Hep), and the amount of immobilized F-Hep was higher on both PLGA/PEO/PgP3.7 and PLGA/PEO/PgP1 than yarns without PgP (PLGA/PEO). We also found that F-Hep was released from both PgP-containing yarns in a sustained manner over 20 days, while over 60% of F-Hep was released within 4 h from PLGA/PEO. Finally, we observed that heparin-eluting nanofiber yarns with both PgP1 and PgP3.7 showed significantly longer clotting times than nanofiber yarns without PgP. The clotting time of PLGA/PEO/PgP3.7 was not significantly different than that of free heparin (0.5 μg/mL). These results show that heparin-eluting electrospun nanofiber yarns may offer a basis for the development of microvascular sutures with anticoagulant activity.

Sustained heparin release actuator achieved from thermal and water activated shape memory hydrogels containing main-chain LC units

In this work, liquid crystalline (LC) monomer with two n-decenoyl terminated groups was synthesized and applied into shape memory hydrogels containing main-chain LC unit by Michael addition polymerization. The liquid crystalline textures of LC monomer and hydrogels were determined by polarized optical microscopy. Thermal and water activated shape memory properties were investigated. And the shape memory properties were improved by incorporating main chain LC unit into hydrogels. The biocompatibility was evaluated by the cytotoxicity test and all these hydrogels illustrated no cytotoxicity. The good biocompatibility and reinforced shape memory properties with shape fixity ratio higher than 96% and shape recovery ratio higher than 93%, indicating a new idea to prepare shape memory hydrogels by introducing main-chain mesogenic units into hydrogels in the safe application of smart biomedical areas. Finally, water-activated actuators were prepared and could change themselves into “C” or “S” shape in water at 25 °C with about 20 min. And through in vitro heparin release of hydrogel and actuator investigation, more sustained heparin release performance of actuator was observed in our study. This indicated that the heparin loaded actuator would have potential application in anticoagulant scaffold by combining the sustained heparin delivery character and the shape self-changing character of water-activated actuators.

Multifunctional coatings that mimic the endothelium: surface bound active heparin nanoparticles with in situ generation of nitric oxide from nitrosothiols.

Multifunctional coatings that mimic the endothelial function in terms of nitric oxide generation and membrane-bound active heparin species are prepared via the immobilization of cystamine-modified heparin/polyethyleneimine (Hep-Cys/PEI) nanoparticles. Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) were conducted to confirm the coating formation. Functions of active heparin release and nitric oxide (NO) generation are obtained on the material surface after the immobilization of Hep-Cys/PEI nanoparticles. Moreover, a nanoparticle-immobilized coating is sufficiently flexible to resist the deformation of a 316L SS stent without any destruction. With the introduction of heparin, the antithrombin III (AT-III) binding ability was significantly enhanced with prolonged APTT time. Besides, a Hep-Cys/PEI nanoparticle immobilized coating surface not only significantly suppressed the platelet adhesion and activation, but also promoted EC proliferation and inhibited SMC proliferation. Besides, a milder tissue response was observed on the NP immobilized surface. With the synergistic effect of heparin and nitric oxide generating moieties, such multifunctional coatings presented potential for the modification of vascular materials.

Preparation and characterization of self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin using hydrophobic complexation by cationic polymer of β-cyclodextrin

Objective: The aim of this study was the preparation of a self nano-emulsifying drug delivery system (SNEDDS) for oral delivery of heparin.Significance: Preparation of hydrophobic complexes between heparin as the hydrophilic macromolecule and cationic polymer of β-cyclodextrin (CPβCD) was considered for preparation of orally administered SNEDDS in which the drug incorporated in internal oil phase of O/W nano-droplets.Methods: Hydrophobic complexes of heparin-CPβCD were prepared by electrostatic interaction. The lipophilic feature of complexes was characterized by determining their partition co-efficients. SNEDDS prototypes were prepared by mixing liquid paraffin, Tween 80, propylene glycol and ethanol, diluted 1:100 in an aqueous medium. Central composite response surface methodology was applied for statistical optimization. Independent variables were the amount of liquid paraffin and the amount of Tween 80, while responses were size and poly dispersity index (PdI). Optimized SNEDDS were studied morphologically using transmission electron microscopy (TEM). In vitro release of heparin was studied in the simulated gastric and simulated intestinal media.Results: The data revealed that in molar ratio 1:3 (heparin:CPβCD), the n-octanol recovery was maximized and reached 67.6 ± 11.86%. Size, PdI, zeta potential, EE% in gastric medium and EE% in intestinal medium for optimized nano-droplets were reported as 307 ± 30.51 nm, 0.236 ± 0.02, +2.1 ± 0.66 mV, 90.2 ± 0.04 and 96.1 ± 0.73%, respectively. Microscopic images revealed spherical nano-droplets. The obtained data revealed no burst release of heparin from nano-droplets.Conclusions: The obtained results indicate that SNEDDS could be regarded as a good candidate for oral delivery of heparin as the hydrophilic macromolecule.

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration.

Adaptive release of heparin from anticoagulant hydrogels triggered by different blood coagulation factors.

Feedback-controlled anticoagulant hydrogels were formed by crosslinking the anticoagulant heparin with star-shaped poly(ethylene glycol) using peptide linkers, which are selectively cleaved by different activated blood coagulation factors acting as proteolytic enzymes. Various cleavable peptide units, differing either in their thrombin turnover rates or in their responsiveness to factors activated earlier in the course of blood coagulation, were used for the formation of the biohybrid materials. Release triggered by the early coagulation factors Xa (FXa) or FXIIa/kallikrein was shown to enhance the efficiency of the released anticoagulant. Furthermore, FXa-cleavable gels enabled a faster release of heparin, which was attributed to the lower affinity of the factor for heparin. Combining early and fast responses, FXa-cleavable gels were shown to provide anticoagulant protection of biomaterial surfaces at low levels of released heparin in human whole-blood incubation experiments. The results demonstrate the potential for employing biomolecular circuits in the design of functional biomaterials to tailor the adaptive delivery of bioactive molecules.

Heparin Contained Multilayer Composite Coatings on NiTi Alloy By Electrochemical Methods for Reducing in-Stent Restenosis

Although the initial success of bare metal stents (BMS) has significantly reduced the restenosis rate from 35% for Percutaneous transluminal coronary angioplasty (PTCA) to 25%, the biological mechanism such as smooth muscle cell proliferation and neointimal hyperplasia may still induce in-stent restenosis (ISR). Therefore, some drug eluting stents have been introduced to reduce ISR. In this study, heparin (Hep) combined with calcium phosphate (CaP) and gelatin (Gel) was co-deposited on NiTi alloy by electrochemical methods in order to fabricate the sustained heparin releasing system for promoting the hemo-compatibility of NiTi substrate. Polarization tests were carried out in several solutions to investigate deposition mechanisms. Heparin contained composite coatings are characterized by X-ray diffractometry (XRD), Field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), toluidine blue colorimetric assay, UV-visible spectrometer and kinetic clotting tests. The consequences indicate that heparin accompanied with CaP, and Gel through ionic bonds can be loaded on the NiTi alloy, respectively. The post porous HA coating can enhance the drug content from 147.06±68.66 of the single layer coating (CaP-Hep) to 191.58±11.87 of the bilayer coating (HA/CaP-Hep) and further to 324.87±4.94 μg/cm2 of the trilayer coating (HA/CaP-Hep/Gel-Hep) by adding the third layer which also results in the in vitro heparin release prolonging from 1 day burst to more than 35 days sustaining release. As the result of clotting tests, drug loaded composite coatings reveal good anticoagulant property which is proportional to the cumulative content of drug release in an hour, indicating no denaturalization of heparin found during the electrochemical process. Keywords: Ni-Ti alloy; in-stent restenosis (ISR); heparin; calcium phosphate; gelatin

Coaxial electrospinning multicomponent functional controlled-release vascular graft: Optimization of graft properties

Small diameter vascular grafts possessing desirable biocompatibility and suitable mechanical properties have become an urgent clinic demand. Herein, heparin loaded fibrous grafts of collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) (PLCL) were successfully fabricated via coaxial electrospinning. By controlling the concentration of heparin and the ratio of collagen/chitosan/PLCL, most grafts had the heparin encapsulation efficiency higher than 70%, and the heparin presented sustained release for more than 45 days. Particularly, such multicomponent grafts had relative low initial burst release, and after heparin releasing for 3 weeks, the grafts still showed good anti-platelet adhesion ability. In addition, along with the excellent cell biocompatibility, the fabricated grafts possessed suitable mechanical properties including good tensile strength, suture retention strength, burst pressure and compliance which could well match the native blood vessels. Thus, the optimized graft properties could be properly addressed for vascular tissue application via coaxial electrospinning.

Bi-layered electrospun nanofibrous polyurethane-gelatin scaffold with targeted heparin release profiles for tissue engineering applications

Abstract Tissue engineering is a biotechnology that is used to develop biological substitutes to restore, maintain, or improve functions. Thus, the porous scaffolds are used to accommodate cells in tissue engineering. In this research, three dimensional (3D) bi-layered polyurethane (PU)-gelatin nanofibrous scaffolds were prepared by the electrospinning method, after which the capability of the released heparin as an anti-coagulation factor was evaluated. Electrospinning has been extensively investigated for the preparation of fibers that exhibit a high surface area to volume ratio. Results showed that scanning electron microscopy (SEM) micrographs exhibited a smooth surface as well as a highly porous and bead-free structure, in which fibers were distributed in the range of 100–600 nm. The modulus and ultimate tensile strength (UTS) decreased and increased, respectively, after crosslinking the reaction of polymers. This process also reduced swelling ratio, the hydrolytic biodegradation rate, and the release rate as a function of time. Moreover, an in vitro assay demonstrated that 3D nanofibrous scaffolds supported L929 fibroblast cell viability and that cells adhered and spread on the fibers. Based on the obtained results, the heparin-loaded electrospinning nanofibrous scaffolds have initial physicochemical and mechanical properties to protect neo-tissue formation.

Multi-component hybrid hydrogels - understanding the extent of orthogonal assembly and its impact on controlled release.

This paper reports self-assembled multi-component hybrid hydrogels including a range of nanoscale systems and characterizes the extent to which each component maintains its own unique functionality, demonstrating that multi-functionality can be achieved by simply mixing carefully-chosen constituents. Specifically, the individual components are: (i) pH-activated low-molecular-weight gelator (LMWG) 1,3;2,4-dibenzylidenesorbitol-4',4''-dicarboxylic acid (DBS-COOH), (ii) thermally-activated polymer gelator (PG) agarose, (iii) anionic biopolymer heparin, and (iv) cationic self-assembled multivalent (SAMul) micelles capable of binding heparin. The LMWG still self-assembles in the presence of PG agarose, is slightly modified on the nanoscale by heparin, but is totally disrupted by the micelles. However, if the SAMul micelles are bound to heparin, DBS-COOH self-assembly is largely unaffected. The LMWG endows hybrid materials with pH-responsive behavior, while the PG provides mechanical robustness. The rate of heparin release can be controlled through network density and composition, with the LMWG and PG behaving differently in this regard, while the presence of the heparin binder completely inhibits heparin release through complexation. This study demonstrates that a multi-component approach can yield exquisite control over self-assembled materials. We reason that controlling orthogonality in such systems will underpin further development of controlled release systems with biomedical applications.