Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections.

Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization. The unique physiology and altered airway environment provide an ideal niche for bacteria to change their phenotype often becoming resistant to current treatments. Colonization with multiple pathogens at the same time further complicate treatment algorithms, requiring drug combinations that can challenge CF patient tolerance to treatment. The goal of this research initiative was to explore the utilization of a microparticle antibiotic delivery system, which could provide localized and sustained antibiotic dosing. The outcome of this work demonstrates the feasibility of providing efficient localized delivery of antibiotics to manage infection using both preclinical in vitro and in vivo CF infection models. The studies outlined in this manuscript demonstrate the proof-of-concept and unique capacity of polymerized cyclodextrin microparticles to provide site-directed management of pulmonary infections.

Polymer Additives to Personal Protective Equipment can Inactivate Pathogens.

Face masks have been proven to be medicine's best public health tool for preventing transmission of airborne pathogens. However, in situations with continuous exposure, lower quality and "do-it-yourself" face masks cannot provide adequate protection against pathogens, especially when mishandled. In addition, the use of multiple face masks each day places a strain on personal protective equipment (PPE) supply and is not environmentally sustainable. Therefore, there is a significant clinical and commercial need for a reusable, pathogen-inactivating face mask. Herein, we propose adding quaternary poly(dimethylaminohexadecyl methacrylate), q(PDMAHDM), abbreviated to q(PDM), to existing fabric networks to generate "contact-killing" face masks-effectively turning cotton, polypropylene, and polyester into pathogen resistant materials. It was found that q(PDM)-integrated face masks were able to inactivate both Gram-positive and Gram-negative bacteria in liquid culture and aerosolized droplets. Furthermore, q(PDM) was electrospun into homogeneous polymer fibers, which makes the polymer practical for low-cost, scaled-up production.

Grafting of short elastin-like peptides using an electric field.

Surface-grafted elastin has found a wide range of uses such as sensing, tissue engineering and capture/release applications because of its ability to undergo stimuli-responsive phase transition. While various methods exist to control surface grafting in general, it is still difficult to control orientation as attachment occurs. This study investigates using an electric field as a new approach to control the surface-grafting of short elastin-like polypeptide (ELP). Characterization of ELP grafting to gold via quartz crystal microbalance with dissipation, atomic force microscopy and temperature ramping experiments revealed that the charge/hydrophobicity of the peptides, rearrangement kinetics and an applied electric field impacted the grafted morphology of ELP. Specifically, an ELP with a negative charge on the opposite end of the surface-binding moiety assembled in a more upright orientation, and a sufficient electric field pushed the charge away from the surface compared to when the same peptide was assembled in no electric field. In addition, this study demonstrated that assembling charged ELP in an applied electric field impacts transition behavior. Overall, this study reveals new strategies for achieving desirable and predictable surface properties of surface-bound ELP.

Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics.

While peptide and protein therapeutics have made tremendous advances in clinical treatments over the past few decades, they have been largely hindered by their ability to be effectively delivered to patients. While bolus parenteral injections have become standard clinical practice, they are insufficient to treat diseases that require sustained, local release of therapeutics. Cyclodextrin-based polymers (pCD) have been utilized as a platform to extend the local delivery of small-molecule hydrophobic drugs by leveraging hydrophobic-driven thermodynamic interactions between pCD and payload to extend its release, which has seen success both in vitro and in vivo. Herein, we proposed the novel synthesis of protein-polymer conjugates that are capped with a "high affinity" adamantane. Using bovine serum albumin as a model protein, and anti-interleukin 10 monoclonal antibodies as a functional example, we outline the synthesis of novel protein-polymer conjugates that, when coupled with cyclodextrin delivery platforms, can maintain a sustained release of up to 65 days without largely sacrificing protein structure/function which has significant clinical applications in local antibody-based treatments for immune diseases, cancers, and diabetes.

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi-Window Release during Bone Reconstruction.

Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft. Local recurrence remains an important and devastating problem, therefore, a system capable of locally delivering chemotherapeutics will present unique advantages. In this work, a refillable chemotherapeutic (doxorubicin, DOX) delivery platform comprised of PMMA bone cement and insoluble γ-cyclodextrin (γ-CD) polymeric microparticles is developed and explored towards application as a temporary adjuvant chemotherapeutic spacer. The system is characterized for porosity, mechanical strength, DOX filling and refilling capacity, elution kinetics, and cytotoxicity. Since residual chemotherapeutics can adversely impact bone healing, it is important that virtually all DOX be released from material. Composites containing 15 wt% γ-CD microparticles demonstrate 100% DOX release within 100 days, whereas only 6% DOX is liberated from PMMA with free DOX over same period. Refillable properties of PMMA composite system may find utility for customizing dosing regimens. Findings suggest that PMMA composites can have potential as chemotherapeutic delivery platforms to assist in bone reconstruction.

Injectable Extracellular Matrix Microparticles Promote Heart Regeneration in Mice with Post-ischemic Heart Injury.

Ischemic heart injury causes permanent cardiomyocyte loss and fibrosis impairing cardiac function. Tissue derived biomaterials have shown promise as an injectable treatment for the post-ischemic heart. Specifically, decellularized extracellular matrix (dECM) is a protein rich suspension that forms a therapeutic hydrogel once injected and improves the heart post-injury response in rodents and pig models. Current dECM-derived biomaterials are delivered to the heart as a liquid dECM hydrogel precursor or colloidal suspension, which gels over several minutes. To increase the functionality of the dECM therapy, an injectable solid dECM microparticle formulation derived from heart tissue to control sizing and extend stability in aqueous conditions is developed. When delivered into the infarcted mouse heart, these dECM microparticles protect cardiac function promote vessel density and reduce left ventricular remodeling by sustained delivery of biomolecules. Longer retention, higher stiffness, and slower protein release of dECM microparticles are noted compared to liquid dECM hydrogel precursor. In addition, the dECM microparticle can be developed as a platform for macromolecule delivery. Together, the results suggest that dECM microparticles can be developed as a modular therapy for heart injury.

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo.

While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to in vivo orthopedic implant-associated infection models, the properties (e.g., degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant in vivo models. The antimicrobial materials are then incorporated into in vivo implant models to evaluate the efficacy of using the material to prevent or treat implant-associated infections. Recent technological advances such as 3D-printing, bacterial genomic sequencing, and real-time in vivo imaging of infection and inflammation have contributed to the development of preclinical implant-associated infection models that more effectively recapitulate the clinical presentation of infections and improve the evaluation of antimicrobial materials. This Review highlights the advantages and limitations of antimicrobial materials used in conjunction with orthopedic implants for the prevention and treatment of orthopedic implant-associated infections and discusses how these materials are evaluated in preclinical in vivo models. This analysis serves as a resource for biomaterial researchers in the selection of an appropriate orthopedic implant-associated infection preclinical model to evaluate novel antimicrobial materials.

Characterization of Inflammatory and Fibrotic Encapsulation Responses of Implanted Materials with Bacterial Infection.

Medical device infections are costly, while preclinical assessment of antimicrobial properties for new materials is time intensive and imperfect at capturing the interrelated aspects of infection response and wound resolution. Herein, we developed an in vivo model for quantification of inflammatory and biocompatibility responses in the presence of a sustained implant-associated infection. The antimicrobial effectiveness of commercially available polymer materials was compared to that of thermoplastic polyurethane (TPU) materials modified with putative antimicrobial strategies as example test materials. Materials were incubated with bioluminescent Escherichia coli prior to implantation in a dorsal subcutaneous pocket in rats with an additional intraluminal bolus of bacteria. Infection kinetics were monitored with bioluminescence, and inflammatory infiltrate and fibrous capsule thickness were determined from stained histological sections. Our model resulted in a persistent infection, sensitive to antimicrobial effects, as the materials modified with a putative antimicrobial surface were able to significantly reduce the level of infection in animals at day 4 postimplantation with efficacy similar to that of commercially available antimicrobial drug-eluting polymers (positive controls). At day 30 postimplantation, the antimicrobial surface modified TPU tubing was found to promote complete elimination of intraluminal bacteria in the absence of antibiotics. Differences were also measurable in acute inflammation, as Wright-Giemsa staining demonstrated reduced inflammatory cell infiltration at day 4 postimplantation for antimicrobial TPU materials. Additionally, antimicrobial materials exhibited reduced fibrous capsule thickness coinciding with infection resolution, as compared to unmodified TPU controls. The developed model can be utilized for testing antimicrobial polymers in the context of a prolonged infection while also revealing concurrent differences in the infiltrating immune cell profiles and fibrous capsule thickness, thus improving the relevance of preclinical medical device material testing.

Ultrasound Triggered Drug Release from Affinity-Based ß-Cyclodextrin Polymers for Infection Control.

This work demonstrates a slow, sustained drug delivery system that provides on-demand delivery bursts through the application of pulsed therapeutic ultrasound (TUS). Insoluble ß-cyclodextrin-polymer (pCD) disks were loaded with a saturated antibiotic solution of rifampicin (RIF) and used for drug delivery studies. To obtain on-demand release from the implants, TUS was applied at an intensity of 1.8 W/cm2. The therapeutic efficacy of the combination treatment was assessed in bacterial culture via an in vitro Staphylococcus aureus bioluminescence assay. The results demonstrated that the application of pulsed TUS at 3 MHz and 1.8 W/cm2 to pCD implants leads to a significantly higher short-term burst in the drug release rate compared to samples not treated with TUS. The addition of TUS increased the drug release by 100% within 4 days. The pCD disk + RIF stimulated with TUS showed a comparatively higher bacterial eradication with CFU/mL of 4.277E+09, and 8.00E+08 at 1 and 24 h compared with control treated bacteria at 1.48E+10. Overall, these results suggest that the addition of pulsed TUS could be an effective technology to noninvasively expedite antibiotic release on demand at desired intervals.

Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss.

Antibiotic-loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load-bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug-filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved. However, the mechanical strengths of PMMA is reduced. In order to decrease the mechanical loss, modified CD microparticles (PMMA-CD) are synthesized that contain covalently appended PMMA chains. The compressive strengths, handling characteristics, and refilling ability of PMMA cement with PMMA-CD are evaluated. Specifically, up to a 13.7% increase in compressive strength is observed when unmodified CD is substituted with PMMA-CD in PMMA samples with 10 wt% CD microparticles. Additionally, a 13.3% increase in working time, a 7.5% decrease in maximum polymerization temperature, and up to a 32.1% increase in amount of drug refilled are observed with the addition of 10 wt% CD PMMA-CD into PMMA in comparison to plain PMMA without CD microparticles.

Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue.

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections. Previous work demonstrated efficacy of incorporating insoluble cyclodextrin (CD) microparticles into PMMA to improve antibiotic release and allow for post-implantation drug refilling to occur in a tissue-mimicking model. To simulate how antibiotic refilling may be possible in more physiologically relevant models, this work investigated development of bone and muscle refilling models. The bone refilling model involved embedding PMMA-CD into rabbit femur and administering antibiotic via intraosseous infusion. Muscle tissue refilling model involved implanting PMMA-CD beads in bovine muscle tissue and administering antibiotic via tissue injection. Duration of antimicrobial activity of refilled PMMA-CD was evaluated. PMMA-CD composite in bone and muscle tissue models was capable of being refilled with antibiotics and resulted in prolonged antimicrobial activity. PMMA-CD provided sustained and on-demand antimicrobial activity without removal of implant if infection develops. Intraosseous infusion appeared to be a viable technique to enable refilling of PMMA-CD after implantation in bone, reporting for the first time the ability to refill PMMA in bone.

Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291.

As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles-specifically, ß-CD microparticles (ß-CD MPs)-to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week.

Nonthermal plasma treatment of polymers modulates biological fouling but can cause material embrittlement.

Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is often thought to have negligible effects on the bulk properties of prosthetic substrates given that it alters the surface chemistry on only the outermost few nanometers of material. However, no studies to date have systematically explored the effects of plasma exposure on both the surface and bulk properties of a biomaterial. This work examines the time-dependent effects of a nonthermal plasma on the surface and bulk (i.e. mechanical) properties of polymeric implants, specifically polypropylene surgical meshes and sutures. Findings suggest that plasma exposure improved resistance to fibrinogen adsorption and Escherichia coli attachment, and promoted mammalian fibroblast attachment, although increased duration of exposure resulted in a state of diminishing returns. At the same time, it was observed that plasma exposure can be detrimental to the material properties of individual filaments (i.e. sutures), as well as the structural characteristics of knitted meshes, with longer exposures resulting in further embrittlement and larger changes in anisotropic behavior. Though there are few guidelines regarding appropriate mechanical properties of surgical textiles, the results from this investigation imply that there are ultimate exposure limits for plasma-based treatments of polymeric implant materials when structural properties must be preserved, and that the effects of a plasma on a given biomaterial should be examined carefully before translation to a clinical scenario.

A Polymeric Delivery System Enables Controlled Release of Genipin for Spatially-Confined In Situ Crosslinking of Injured Connective Tissues.

An emerging approach toward repair of connective tissues applies exogenous crosslinkers to mechanically augment injured structures in vivo. One crosslinker that has been explored for this purpose is the plant-derived small molecule genipin. However, genipin's high reactivity to primary amines in proteins, small size, and high diffusion coefficient necessitate localizing and controlling its delivery to avoid off-target or adverse effects. In this study, genipin-loaded polymers were evaluated for sustained local administration. Insoluble polymers comprising subunits of α-, ß-, or γ-cyclodextrin, cyclic oligosaccharides possessing increasing cavity sizes, were compared to polymers comprising subunits of the non-cyclic polysaccharide dextran. Polymers made from ß-cyclodextrin showed prolonged genipin release for over ten times longer than polymers made from α- or γ-cyclodextrins or dextran, indicating that genipin possesses molecular affinity for the ß-cyclodextrin cavity. Modeling of complexation between genipin and cyclodextrin hosts supported this finding. Genipin released from all polymers was confirmed to be functional by exogenous collagen crosslinking through fluorometric and mechanical readouts. Co-incubation of genipin-loaded polymers with bovine tendon explants showed genipin crosslink-mediated coloration that was confined to the sites of exposure. Altogether, results indicate that host-guest interactions within a polymeric delivery vehicle can help to control and confine genipin release.

Affinity-Based Polymers Provide Long-Term Immunotherapeutic Drug Delivery Across Particle Size Ranges Optimal for Macrophage Targeting.

Drug delivery to specific arms of the immune system can be technically challenging to provide prolonged drug release while limiting off-target toxicity given the limitations of current drug delivery systems. In this work, we test the design of a cyclodextrin (CD) polymer platform to extend immunomodulatory drug delivery via affinity interactions for sustained release at multiple size scales. The parameter space of synthesis variables influencing particle nucleation and growth (pre-incubation time and stirring speed) and post-synthesis grinding effects on resulting particle diameter were characterized. We demonstrate that polymerized CD forms exhibit size-independent release profiles of the small molecule drug lenalidomide (LND) and can provide improved drug delivery profiles versus macro-scale CD polymer disks in part due to increased loading efficiency. CD polymer microparticles and smaller, ground particles demonstrated no significant cytotoxicity as compared to the base CD monomer when co-incubated with fibroblasts. Uptake of ground CD particles was significantly higher following incubation with RAW 264.7 macrophages in culture over standard CD microparticles. Thus, the affinity/structure properties afforded by polymerized CD allow particle size to be modified to affect cellular uptake profiles independently of drug release rate for applications in cell-targeted drug delivery.

Periadventitial Delivery of Simvastatin-Loaded Microparticles Attenuate Venous Neointimal Hyperplasia Associated With Arteriovenous Fistula.

Background Venous neointimal hyperplasia and venous stenosis (VS) formation can result in a decrease in arteriovenous fistula (AVF) patency in patients with end-stage renal disease. There are limited therapies that prevent VNH/VS. Systemic delivery of simvastatin has been shown to reduce VNH/VS but local delivery may help decrease the side effects associated with statin use. We determined if microparticles (MP) composed of cyclodextrins loaded with simvastatin (MP-SV) could reduce VS/VNH using a murine arteriovenous fistula model with chronic kidney disease. Methods and Results Male C57BL/6J mice underwent nephrectomy to induce chronic kidney disease. Four weeks later, an arteriovenous fistula was placed and animals were randomized to 3 groups: 20 µL of PBS or 20 µL of PBS with 16.6 mg/mL of either MP or MP-SV. Animals were euthanized 3 days later and the outflow veins were harvested for quantitative reverse transcriptase-polymerase chain reaction analysis and 28 days later for immunohistochemistical staining with morphometric analysis. Doppler ultrasound was performed weekly. Gene expression of vascular endothelial growth factor-A (Vegf-A), matrix metalloproteinase-9 (Mmp-9), transforming growth factor beta 1 (Tgf-ß1), and monocyte chemoattractant protein-1 (Mcp-1) were significantly decreased in MP-SV treated vessels compared with controls. There was a significant decrease in the neointimal area, cell proliferation, inflammation, and fibrosis, with an increase in apoptosis and peak velocity in MP-SV treated outflow veins. MP-SV treated fibroblasts when exposed to hypoxic injury had decreased gene expression of Vegf-A and Mmp-9. Conclusions In experimental arteriovenous fistulas, periadventitial delivery of MP-SV decreased gene expression of Vegf-A, Mmp-9, Tgf-ß1 and Mcp-1, VNH/VS, inflammation, and fibrosis.

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes.

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

Elucidating the Structure-Function Relationship of Solvent and Cross-Linker on Affinity-Based Release from Cyclodextrin Hydrogels.

Minocycline (MNC) is a tetracycline antibiotic capable of associating with cyclodextrin (CD), and it is a frontline drug for many instances of implant infection. Due to its broad-spectrum activity and long half-life, MNC represents an ideal drug for localized delivery; however, classic polymer formulations, particularly hydrogels, result in biphasic release less suitable for sustained anti-microbial action. A polymer delivery system capable of sustained, steady drug delivery rates poses an attractive target to maximize the antimicrobial activity of MNC. Here, we formed insoluble hydrogels of polymerized CD (pCD) with a range of crosslinking densities, and then assessed loading, release, and antimicrobial activity of MNC. MNC loads between 5-12 wt % and releases from pCD hydrogels for >14 days. pCD loaded with MNC shows extended antimicrobial activity against S. aureus for >40 days and E. coli for >70 days. We evaluated a range of water/ethanol blends to test our hypothesis that solvent polarity will impact drug-CD association as a function of hydrogel swelling and crosslinking. Increased polymer crosslinking and decreased solvent polarity both reduced MNC loading, but solvent polarity showed a dramatic reduction independent of hydrogel swelling. Due to its high solubility and excellent delivery profile, MNC represents a unique drug to probe the structure-function relationship between drug, affinity group, and polymer crosslinking ratio.

Affinity Effects on the Release of Non-Conventional Antifibrotics from Polymer Depots.

For many chronic fibrotic conditions, there is a need for local, sustained antifibrotic drug delivery. A recent trend in the pharmaceutical industry is the repurposing of approved drugs. This paper investigates drugs that are classically used for anthelmintic activity (pyrvinium pamoate (PYR)), inhibition of adrenal steroidgenesis (metyrapone (MTP)), bactericidal effect (rifampicin (RIF), and treating iron/aluminum toxicity (deferoxamine mesylate (DFOA)), but are also under investigation for their potential positive effect in wound healing. In this role, they have not previously been tested in a localized delivery system suitable for obtaining the release for the weeks-to-months timecourse needed for wound resolution. Herein, two cyclodextrin-based polymer systems, disks and microparticles, are demonstrated to provide the long-term release of all four tested non-conventional wound-healing drugs for up to 30 days. Higher drug affinity binding, as determined from PyRx binding simulations and surface plasmon resonance in vitro, corresponded with extended release amounts, while drug molecular weight and solubility correlated with the improved drug loading efficiency of cyclodextrin polymers. These results, combined, demonstrate that leveraging affinity interactions, in combination with drug choice, can extend the sustained release of drugs with an alternative, complimentary action to resolve wound-healing and reduce fibrotic processes.

Repurposing biodegradable tissue engineering scaffolds for localized chemotherapeutic delivery.

While highly porous biodegradable sponges have typically been used as tissue engineering scaffolds, they could be applicable in settings requiring drug delivery. Since most drug delivery devices are intentionally solid, nonporous polymers, a detailed structure-function relationship of delivery from a porous degradable sponges would allow researchers to develop such devices for either delivery alone, or in conjunction with tissue engineering. Two fabrication techniques (salt-leaching and solvent-quenching) were used to prepare several different variations of poly(DL-lactide-glycolide) and poly(caprolactone)-co-poly(lactide) porous sponges. Upon fabrication, an in-depth structure-function analysis was carried out where the functions of loading capacity and release profile of cisplatin, as a model drug, were evaluated in terms of the swelling, porosity, and degradation properties of the sponges. Swelling, pore volume fraction, and the number of pores per volume were all found to be positively correlated with both the loading capacity and amount of cisplatin released after 2 hr. Knowledge of these relationships can be used to assist in the design of other porous delivery systems.