Controlled Drug Release from Biodegradable Polymer Matrix Loaded in Microcontainers Using Hot Punching.
ABSTRACT: Microcontainers are reservoir-based advanced drug delivery systems (DDS) that have proven to increase the bioavailibity of the small-molecule drugs, targeting of biomolecules, protection of vaccines and improved treatment of Pseudomonas aeruginosa. However, high-throughput loading of these micron-sized devices with drug has been challenging. Hot punching is a new technique that is a fast, simple and single-step process where the microdevices are themselves used as mold to punch biocompatible and biodegradable drug-polymer films, thereby loading the containers. Here, we investigate the effect of hot punching on the drug distribution as well as drug release from the loaded drug-polymer matrices. Zero-order sustained drug release is observed for the model drug Furosemide embedded in biodegradable polymer, Poly-?-caprolactone, which is attributed to the unique spatial distribution of Furosemide during the loading process.
Project description:Microfabricated devices have been introduced as a promising approach to overcome some of the challenges related to oral administration of drugs and, thereby, improve their oral bioavailability. In this study, we fabricate biodegradable microcontainers with different polymers, namely poly-?-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) 50:50 and PLGA 75:25 by hot punching. The mucoadhesion of the microcontainers is assessed with an ex vivo retention model on porcine intestinal tissue. Finally, in vitro degradation studies of the biodegradable microcontainers are completed for six weeks in simulated intestinal medium with the addition of pancreatic enzymes. Through SEM inspection, the PLGA 50:50 microcontainers show the first signs of degradation already after two weeks and complete degradation within four weeks, while the other polymers slowly degrade in the medium over several weeks.
Project description:We demonstrate mass-producible, mobile, self-loading microcontainers that can be used to encapsulate both non-living and living objects, thus forming three-dimensionally patterned, mobile microwells.
Project description:Versatile all-nanocomposite capped microcontainers are made using layer-by-layer (LBL) assembly. The microcontainers can act as inert packaging with slow/controlled release for virtually any type of encapsulating material based on clay nanocomposites 3D molded by PDMS templates and capped with another LBL film.
Project description:Significant and promising advances have been made in the polymer field for controlled and sustained bioactive delivery. Traditionally, small molecule bioactives have been physically incorporated into biodegradable polymers; however, chemical incorporation allows for higher drug loading, more controlled release, and enhanced processability. Moreover, the advent of bioactive-containing monomer polymerization and hydrolytic biodegradability allows for tunable bioactive loading without yielding a polymer residue. In this review, we highlight the chemical incorporation of different bioactive classes into novel biodegradable and biocompatible polymers. The polymer design, synthesis, and formulation are summarized in addition to the evaluation of bioactivity retention upon release via in vitro and in vivo studies.
Project description:Development of a novel filter material is urgently required for replacing the high-cost flue gas purification technology in the simultaneous removal of both fine dust and Nitrogen oxides (NOx). In this study; polyphenylene sulfide (PPS) needle-punching fibrous felts (NPFF) were employed as the filter material to remove the fine dust; and in the meanwhile; Mn and Ce oxides were loaded onto the PPS NPFF as the catalyst for selective catalytic reduction of NOx with NH3. Two different pretreatment methods; i.e., sodium alginate (SA) deposition and plasma treatment; were employed to modify the PPS NPFF before the traditional impregnation and thermal treatment processes during the catalyst loading. The results showed that these two pretreatment methods both afforded the PPS NPFF with the enhanced loading rate and stability of Mn/Ce oxides compared to those without any pretreatments; which were significantly beneficial for the denitration application. Moreover; we found that both SA deposition and plasma pre-treated samples presented excellent dust-removal properties; and the filtration efficiency could reach 100% when the particle size of the fine particulates was above 4 ?m. This study demonstrated that our Mn/Ce oxides decorated PPS NPFF have great potential to be applied in the fuel gas purification field; due to their stable structure; handling convenience; and excellent filtration efficiency; as well as high denitration performance.
Project description:Reinforced concrete flat slabs or flat plates continue to be among the most popular floor systems due to speed of construction and inherent flexibility it offers in relation to locations of partitions. However, flat slab/plate floor systems that are deficient in two-way shear strength are susceptible to brittle failure at a slab-column junction that may propagate and lead to progressive collapse of a larger segment of the structural system. Deficiency in two-way shear strength may be due to design/construction errors, material under-strength, or overload. Fiber reinforced polymer (FRP) composite laminates in the form of sheets and/or strips are used in structurally deficient flat slab systems to enhance the two-way shear capacity, flexural strength, stiffness, and ductility. Glass FRP (GFRP) has been used successfully but carbon FRP (CFRP) sheets/strips/laminates are more commonly used as a practical alternative to other expensive and/or challenging methods such column enlargement. This article reviews the literature on the methodology and effectiveness of utilizing FRP sheets/strips and laminates at the column/slab intersection to enhance punching shear strength of flat slabs.
Project description:Self-assembled polymer/porous silicon nanocomposites overcome intracellular and systemic barriers for in vivo application of peptide nucleic acid (PNA) anti-microRNA therapeutics. Porous silicon (PSi) is leveraged as a biodegradable scaffold with high drug-cargo-loading capacity. Functionalization with a diblock polymer improves PSi nanoparticle colloidal stability, in vivo pharmacokinetics, and intracellular bioavailability through endosomal escape, enabling PNA to inhibit miR-122 in vivo.
Project description:The design of drug delivery systems capable of efficiently delivering poorly soluble drugs to target sites still remains a major challenge. Such materials require several different functionalities; typically, these materials should be biodegradable and nontoxic, nonimmunogenic, responsive to their environment, and soluble in aqueous solution while retaining the ability to solubilize hydrophobic drugs. Here, a polypeptide-polymer hybrid of elastin-like polypeptides (ELPs) and poly(2-oxazoline)s (POx) is reported. This paper describes the chemical synthesis, physical characteristics, and drug loading potential of these novel hybrid macromolecules. A novel method is introduced for terminal functionalization of POx with protected maleimide moieties. Following recovery of the maleimide group via a retro Diels-Alder reaction, the consecutive Michael addition of thiol-functionalized ELPs yields the desired protein-polymer conjugate. These conjugates form nanoparticles in aqueous solution capable of solubilizing the anti-cancer drug paclitaxel with up to 8 wt% loading.
Project description:Pulsatile delivery of proteins, in which release occurs over a short time after a period of little or no release, is desirable for many applications. This paper investigates the effect of biodegradable polymer shell thickness on pulsatile protein release from biodegradable polymer microcapsules.Using precision particle fabrication (PPF) technology, monodisperse microcapsules were fabricated encapsulating bovine serum albumin (BSA) in a liquid core surrounded by a drug-free poly(lactide-co-glycolide) (PLG) shell of uniform, controlled thickness from 14 to 19 ?m.When using high molecular weight PLG (Mw 88 kDa), microparticles exhibited the desired core-shell structure with high BSA loading and encapsulation efficiency (55-65%). These particles exhibited very slow release of BSA for several weeks followed by rapid release of 80-90% of the encapsulated BSA within 7 days. Importantly, with increasing shell thickness the starting time of the pulsatile release could be controlled from 25 to 35 days.Biodegradable polymer microcapsules with precisely controlled shell thickness provide pulsatile release with enhanced control of release profiles.
Project description:Renal tubular acidosis (RTA) is a rare disease caused by a defect of urinary acidification. The ammonium chloride loading test is the gold standard method for determining the type of RTA. However, because this test has some side effects (e.g., nausea, vomiting, and stomach discomfort), applying this test for pediatric cases is difficult. Recently, a loading test with the combination of furosemide and fludrocortisone was reported to be an alternative to the ammonium chloride loading test, with 100% sensitivity and specificity in adult's cases. We report the first pediatric case of distal RTA in a patient who was successfully diagnosed by a drug loading test with the combination of furosemide and fludrocortisone without any side effects. We also performed genetic analysis and detected a known pathogenic variant in the SLC4A1 gene. The combination loading test of furosemide and fludrocortisone is a useful and safe diagnostic tool for pediatric cases of RTA.