Capsules For Drug Delivery Research Articles

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Gilded vaterite optothermal transport in a bubble

Laser beams, capable of controlling the mechanical motion of micron-scale objects, can serve as a tool, enabling investigations of numerous interaction scenarios under full control. Beyond pure electromagnetic interactions, giving rise to conventional gradient forces and radiation pressure, environment-induced thermal effects can play a role and, in certain cases, govern the dynamics. Here we explore a thermocapillary Marangoni effect, which is responsible for creating long-range few hundreds of nano-Newton forces, acting on a bubble around a ‘gilded vaterite’ nanoparticle. Decorating calcium carbonate spherulite (the vaterite) with gold nanoseeds allows tuning its optical absorption and, as a result, controlling its temperature in a solution. We demonstrate that keeping a balance between electromagnetic and thermal interactions allows creating of a stable micron-scale bubble around the particle and maintaining its size over time. The bubbles are shown to remain stable over minutes even after the light source is switched off. The bubbles were shown to swim toward a laser focus for over 400-µm distances across the sample. Optothermal effects, allowing for efficient transport, stable bubble creation, and particle–fluid interaction control, can grant nano-engineered drug delivery capsules with additional functions toward a theragnostic paradigm shift.

Effects of Internal Boundary Layers and Sensitivity on Frequency Response of Shells of Revolution

New applications introduced capsule designs with features that have not been fully analysed in the literature. In this study, thin shells of revolution are used to model drug delivery capsules both with closed and open designs including perforations. The effects of internal boundary layers and sensitivity on frequency response are discussed in the special case with symmetric concentrated load. The simulations are carried out using high-order finite element method and the frequency response is computed with a very accurate low-rank approximation. Due to the propagation of the singularities induced by the concentrated loads, the most energetic responses do not necessarily include a pinch-through at the point of action. In sensitive configurations, the presence of regions with elliptic curvature leads to strong oscillations at lower frequencies. The amplitudes of these oscillations decay as the frequencies increase. For efficient and reliable analysis of such structures, it is necessary to understand the intricate interplay of loading types and geometry, including the effects of the chosen shell models.

Development of a modified hard gelatin capsule for colon-targeted drug delivery of hydrogel-based piroxicam microparticles

Purpose: To develop modified hard gelatin capsules (MHGCs) for colon-specific delivery of hydrogel-based piroxicam microparticles.
 Methods: Solvent evaporation technique was adopted for the microencapsulation of piroxicam using liquid paraffin (PL.MPs) and soybean oil (PS.MPs) which were subsequently encapsulated in MHGCs (water-impervious). Anti-inflammatory and in vitro dissolution studies were conducted on the unencapsulated microparticles (MPs). Furthermore, in vitro colon-specific sequential drug release from impervious capsules was carried out for 2 h at pH 1.2 and 3 h in 6.8, and ≥ 5 h in 7.4, to simulate drug release in the stomach, small intestine, and colon environment, respectively. Differential scanning calorimetry (DSC) analysis was also conducted on the formulations.
 Results: Edema inhibition of PL.MPs and PS.MPs were within the range of 51.0 – 64.0 and 58.0 – 69.0 %, respectively. In vitro colon-specific drug dissolution studies revealed absence, minimal, and highest amounts of drug release from MHGCs in pH 1.2, 6.8 and 7.4 media, respectively. Decreased crystallinity of the microparticles was indicated by a broad endothermic peak.
 Conclusion: The MHGCs hold promise as a potential alternative delivery system for hydrogel-based piroxicam microparticles designed for colon-targeted drug delivery. However, clinical development studies are required.

Cisplatin-Conjugated Polyurethane Capsule for Dual Drug Delivery to a Cancer Cell.

This paper describes the synthesis of a polymer-prodrug conjugate, its aqueous self-assembly, noncovalent encapsulation of a second drug, and stimuli-responsive intracellular dual drug delivery. Condensation polymerization between a functionalized diol and a commercially available diisocyanate in the presence of poly(ethylene glycol) hydroxide (PEG-OH) as the chain stopper produces an ABA-type amphiphilic block copolymer (PU-1) in one pot, with the middle hydrophobic block being a polyurethane containing a pendant tert-butyloxycarbonyl (Boc)-protected amine in every repeating unit. Deprotection of the Boc group, followed by covalent attachment of the Pt(IV) prodrug using the pendant amine groups, produces the polymer-prodrug conjugate PU-Pt-1, which aggregates to nanocapsule-like structures in water with a hydrophilic interior. In the presence of sodium ascorbate, the Pt(IV) prodrug can be detached from the polymer backbone, producing the active Pt(II) drug. Cell culture studies show appreciable cell viability by the parent polymer. However, the polymer-prodrug conjugate nanocapsules exhibit cellular uptake and intracellular release of the active drug under a reducing environment. The capsule-like aggregates of the polymer-prodrug conjugate were used for noncovalent encapsulation of a second drug, doxorubicin (Dox), and Dox-loaded PU-Pt-1 aggregate showed a significantly superior cell killing efficiency compared to either of the individual drugs, highlighting the promising application of such a dual-drug-delivery approach.

Reduction of the in vitro toxicity of elevated concentrations of SPIONLA by its administration through PHBV/curcumin composite microspheres

Superparamagnetic iron oxide nanoparticles have been developed for various biomedical applications for decades. In this work, lauric acid-coated SPION (SPIONLA) were incorporated into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) at different ratios to produce composite microspheres, which were evaluated for their properties, including potential cytotoxicity. Additionally, a phytotherapeutic extract, curcumin, was loaded into the resulting microspheres to develop magnetic drug delivery capsules. The results show a significant improvement in the cytocompatibility after 7 days of SPIONLA administrated in cells through the composite microspheres compared to pristine SPIONLA. The composite also exhibited prolonged cumulative release of curcumin in a simulated body fluid environment. The results confirmed the efficacy of the mixture of PHBV and curcumin in attenuating potential side effects due to direct administration of high initial amounts of SPIONLA while maintaining magnetic properties in the resulting composite. The results add evidence to the potential of these composite devices for targeted drug delivery applications.

Advances in Biodegradable Soft Robots.

Biodegradable soft robots have been proposed for a variety of intelligent applications in soft robotics, flexible electronics, and bionics. Biodegradability offers an extraordinary functional advantage to soft robots for operations accompanying smart shape transformation in response to external stimuli such as heat, pH, and light. This review primarily surveyed the current advanced scientific and engineering strategies for integrating biodegradable materials within stimuli-responsive soft robots. It also focused on the fabrication methodologies of multiscale biodegradable soft robots, and highlighted the role of biodegradable soft robots in enhancing the multifunctional properties of drug delivery capsules, biopsy tools, smart actuators, and sensors. Lastly, the current challenges and perspectives on the future development of intelligent soft robots for operation in real environments were discussed.

Liquid capsules for gastrointestinal drug delivery

Recently, Margossian et al. reported pH-responsive complex coacervates formed by a polyzwitterion and a polyelectrolyte in <i>Nature Communications</i>, which remain intact under acidic conditions (<mml:math><mml:mrow>pH<mml:mo>≤</mml:mo><mml:mn>3</mml:mn></mml:mrow></mml:math>) yet dissolve with increasing pH, suggesting the potential for oral delivery to the gastrointestinal tract.

RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract.

Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap's mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery (P<0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.

A Novel Capsule-Delivered Enteric Drug-Injection Device for Delivery of Systemic Biologics: A Pilot Study in a Porcine Model.

Innovative swallowable capsule technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities to overcome challenges regarding oral delivery of biologics. Here, we report a swallowable capsule for intestinal drug delivery (SCIDD) with the potential of directly injecting biological therapeutics into the insensate small intestine wall. The design, optimization, and validation of the SCIDD's primary subsystems were performed both ex-vivo and in-vivo. The assembled capsule was further tested in vivo to validate the actuation sequence and showed a 70% (n = 17) success rate in an animal model. Additionally, a drug delivery study indicated systemic uptake of adalimumab via SCIDD compared with luminal delivery in the small intestine. The pilot study presented here establishes that the novel platform could be used to orally deliver systemic biologics.

An Overview of Robotic Capsules for Drug Delivery to the Gastrointestinal Tract.

The introduction of capsule endoscopy two decades ago marked the beginning of the “small bowel revolution”. Since then, the rapid evolution of microtechnology has allowed the development of drug delivery systems (DDS) designed to address some of the needs that are not met by standard drug delivery. To overcome the complex anatomy and physiology of the gastrointestinal (GI) tract, several DDS have been developed, including many prototypes being designed, built and eventually produced with ingenious drug-release mechanisms and anchoring systems allowing targeted therapy. This review highlights the currently available systems for drug delivery in the GI tract and discusses the needs, limitations, and future considerations of these technologies.

Abstract 280: Sub-30-nm capsules for drug delivery

Abstract Systemic treatment of cancer using long-circulating nanomedicines is promising due to their passive tumor targeting ability to achieve higher and more selective accumulation in tumors with irregular vascularization, a phenomenon known as extended permeation and retention (EPR) effect.1,2 Clinical use of nanometer-sized carriers, such as Doxil and Abraxane, to deliver chemotherapeutics to solid tumors is proven effective in highly vascularized tumors such as breast cancer, ovarian cancer, multiple myeloma, and Kaposi's sarcoma.3-5 Most nanomedicines that are being developed or approved so far have a diameter of around 100-200 nm for prolonged retention in highly angiogenic and densely vascularized tumors,6 however, they suffer from limited accumulation and poor penetration to the inner core of avascular or hypovascular tumors (such as prostate and pancreatic cancer),7-9 therefore nanomedicines small than 100 nm are more preferred for improved tumor penetration.10,11 Here we present our strategy to form cyclodextrin-based sub-30-nm nanocarriers, which allows easy drug encapsulation, and successful delivery of therapeutics to human tumor xenografts with significantly reduced tumor growth rates and improved survival rates. Citation Format: Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui. Sub-30-nm capsules for drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 280.

Assembly of responsive metal-phenolic network capsules for drug delivery

Assembly of responsive metal-phenolic network capsules for drug delivery

Efficient Synthesis of Folate-Conjugated Hollow Polymeric Capsules for Accurate Drug Delivery to Cancer Cells.

This study presents an efficient and systematic approach to synthesize bioapplicable porous hollow polymeric capsules (HPCs). The hydroxyl-functionalized nanoporous polymers with hollow capsular shapes could be generated via the moderate Friedel-Crafts reaction without using any hard or soft template. The numerous primitive hydroxyl groups on these HPCs were further converted to carboxyl groups. Owing to the abundance of highly branched carboxyl groups on the surface of the HPCs, biomolecules [such as folic acid (FA)] could be covalently decorated on these organic capsules (FA-HPCs) for drug delivery applications. The intrinsic hollow porosities and specific targeting agent offered a maximum drug encapsulation efficiency of up to 86% and drug release of up to 50% in 30 h in an acidic environment. The in vitro studies against cancer cells demonstrated that FA-HPCs exhibited a more efficient cellular uptake and intracellular doxorubicin release than bare HPCs. This efficient approach to fabricate carbonyl-functionalized hollow organic capsules may open avenues for a new type of morphological-controlled nanoporous polymers for various potential bioengineering applications.

Crack self-healing of thermo-responsive shape memory polymers with application to control valves, filtration, and drug delivery capsule

Fracture behavior of Shape Memory Polymers (SMPs) and their self-healing property is one of the up-to-date subjects through the literature, where only a few researches have been conducted. Nowadays, because of the exceptional properties of SMPs and their implementation in 4D printing, they are most taken into attention. In this study, thermomechanical coupling effect on 3D fracture analysis of SMPs in large deformation regime has been investigated. Firstly, a thermo-visco-hyperelastic model is implemented to model the thermomechanical cycle of the SMP in the stress-free strain-recovery as well as the fixed-strain-stress-recovery processes. Motivated by fracture analysis and self-healing properties of SMPs, both 2D and 3D fracture analysis are conducted through various feasibility applications, such as flow control valve, pressure control valve, filtration and drug delivery capsule. Moreover, the ability of the analysis is shown through examining different parameters could affect the SMP response, such strain rate (or applied strain), temperature rate and memory recovery. Finally, the results show the ability of the numerical modeling in the aforesaid applications to design, analyze, and fabricate these applications.

Molecular recognition of isovanillin crosslinked carrageenan biocomposite for drug delivery application

This work aims to evaluate carrageenan as a potential biocomposite for hard capsule in the drug delivery application. The interaction between carrageenan and isovanillin was studied by modeling their molecule electronic surface potential and enthalpy. Simulation results showed that the physical crosslinking is established at two points: hydroxyl (isovanillin)-sulfate (carrageenan) and aldehyde (isovanillin)-hydroxyl (carrageenan) with strong hydrogen bonds (H-bond) lengths of 1.74–1.79 Å. FTIR showed that isovanillin addition increased the intermolecular H-bond up to 57% as the OH-stretching is shifted from 3376 to 3356 cm−1. At 3 wt.% isovanillin concentration, the tensile strength of the biocomposite film increased to 49% and the hard capsule developed from the formulation solution disintegrated in 9 min. Upon contact with water, the H-bonds broke and caused the carrageenan fragments to dissolve in deionized water. The disintegration and mechanical properties of the crosslinked carrageenan biocomposite film made from renewable and low price materials facilitate the application of the film as hard capsules for drug delivery.

Controlled release of sulfasalazine loaded amidated pectin microparticles through Eudragit S 100 coated capsule for management of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a common colonic disorder affecting most of the world population. In order to overcome the IBD, present study was aimed to fabricate the sulfasalazine loaded amidated pectin microparticles by ionic gelation technique. The microparticles were filled in Eudragit S 100 coated hard gelatin capsules for pH and time dependent drug delivery to the colon especially for the treatment of IBD. The effects of variables such as concentration of crosslinking agent (calcium chloride) and amidated pectin-sulfasalazine ratio were optimized through the particle size, zeta potential, % yield, encapsulation efficiency (% EE), swelling index and in vitro drug release. The optimized formulation, F4 exhibited average particle size (463.33 ± 6.72 μm), zeta potential (−32.10 ± 0.80 mV), yield (91.62 ± 1.97%) and EE (95.62 ± 1.21%). The significant swelling index, 0.88 ± 0.02 θ and 0.98 ± 0.03 θ was achieved with F4 at pH 6.8 and pH 7.4 respectively. The F4 showed maximum drug release (91.12 ± 5.11%) in simulated colonic fluid (SCF, pH 7.4) and 98.07 ± 3.92% (P < 0.05) in rat cecal content (RCC, pH 7.4) for 24 h in a sustained manner. It may be due to the drug released through polymer by diffusion-matrix erosion and bacterial degradation of the microparticles. The F4 formulation displayed non-Fickian pattern of drug release. In vivo study in rabbits confirmed that the enteric polymer coated capsule dissolve at colonic pH 7.4 to release the drug from microparticles. The F4 exhibited remarkable stability at room temperature and shelf-life was found to be 3.3 years. Thus, the sulfasalazine loaded amidated pectin microparticles filled in Eudragit S 100 coated hard gelatin capsule was found to be a potential delivery system for management of IBD.

Medical Microrobot — A Drug Delivery Capsule Endoscope with Active Locomotion and Drug Release Mechanism: Proof of Concept

This paper presents a robotic capsule endoscope integrated a targeted drug delivery module (DDM) for digestive diseases treatments. The capsule with a big permanent magnet inside is wirelessly controlled and actively moves to target region in gastrointestinal tract by an electromagnetic actuation system (EMA). DDM is a separated body composed of a drug container and a non-power drug-releasing mechanism. The force to expel drug is generated by carbon dioxide gas pressure coming from a chemical reaction inside a propellant reservoir. Where the chemical reaction is activated by a mechanical mechanism that allows dry chemical powders contacting with water at the target point. A small permanent magnet is utilized to separate reagents and wet paper before drug injection. It is designed to be stable during locomotion by virtue of the attractive force of a big permanent magnet. To trigger releasing mechanism, gradient magnetic field from EMA system is created to push small magnet slide down, which allows reagents drop and contact with water in wet paper. The designed DDM has length of 11 mm and diameter of 11 mm. The proposed robotic capsule could show high potentials to be utilized for therapeutic treatment of digestive diseases in practical clinical sites through simulation and ex-vivo experiments.

Mechanical Properties of Particle Films on Curved Interfaces Probed through Electric Field-Induced Wrinkling of Particle Shells.

Similar to the human skin, a monolayer of packed particles capillary bound to a liquid interface wrinkles when subjected to compressive stress. The induced wrinkles absorb the applied stress and do not disappear unless the stress is removed. Experimental and theoretical investigations of wrinkle formation typically concern flat particle monolayers subjected to uniaxial stress. In this work, we extend the results on wrinkling of particle-covered interfaces to the investigation of mechanical properties of particle films on a curved interface, that is, we study particle shells formed on droplets and subjected to hoop stress. Opposed to flat particle layers where liquid buoyancy alone acts as the effective stiffness, the mechanical properties of particle layers on small droplets are also affected by the surface curvature. We show here that this leads to formation of wrinkles with different characteristic wavelengths compared to those found at flat interfaces. Our experimental results also reveal that the wrinkle wavelength of particle shells is proportional to the square root of particle size and the size of the droplets on which the shells are formed. Wrinkling of particle layers composed of microparticles with diameters ranging from around 1-100 μm was induced using a novel approach combining electrodeformation and electrohydrodynamic flows. We demonstrate that our contactless approach for studying the mechanical properties of particle shells enables estimation of elasticity, particle film thickness, and bending stiffness of particle shells. The proposed approach is insensitive to both particle coverage and electric field strength. In addition, it enables manipulation of particle packing that is intimately linked with formation of wrinkling patterns. With a wide range of applications depending on accurate mechanical properties (e.g., drug-delivery capsules to self-healing materials), this work provides a valuable method to characterize the mechanical properties of shells and tailor their surface properties (i.e., permeability and roughness).

Review on Synthesis of Colloidal Hollow Particles and Their Applications

Hollow latex (HL) particles of polymers or hybrid polymer/inorganic materials have advantages in efficient encapsulation of active ingredients, ability to improve opacity or hiding power, and low density. Due to the flexible design for achieving the desired functionality, polymeric HL particles serve as stimuli-responsive capsules for drug delivery and cosmetics, white pigment for coatings, as well as nanoreactors for the confined reactions. Among numerous studies on the synthesis of HL particles for specific applications, this review article summarizes the recent works on the HL particles prepared from both synthetic and natural polymers. The template-based methods using sacrificial hard or soft template, self-templating, and nonsacrificial techniques are described. Various factors affecting morphologies and properties of HL particles are discussed in detail. Their applications in coatings, cosmetics, biomedicines, electronics, and others are also presented.