Microcapsules for Enhanced Cargo Retention and Diversity

Prevention of undesired leakage of encapsulated materials prior to triggered release presents a technological challenge for the practical application of microcapsule technologies in agriculture, drug delivery, and cosmetics. A microfluidic approach is reported to fabricate perfluoropolyether (PFPE)‐based microcapsules with a high core‐shell ratio that show enhanced retention of encapsulated actives. For the PFPE capsules, less than 2% leakage of encapsulated model compounds, including Allura Red and CaCl₂, over a four week trial period is observed. In addition, PFPE capsules allow cargo diversity by the fabrication of capsules with either a water‐in‐oil emulsion or an organic solvent as core. Capsules with a toluene‐based core begin a sustained release of hydrophobic model encapsulants immediately upon immersion in an organic continuous phase. The major contribution on the release kinetics stems from the toluene in the core. Furthermore, degradable silica particles are incorporated to confer porosity and functionality to the otherwise chemically inert PFPE‐based polymer shell. These results demonstrate the capability of PFPE capsules with large core–shell ratios to retain diverse sets of cargo for extended periods and make them valuable for controlled release applications that require a low residual footprint of the shell material.     

Multi‐Drug‐Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly‐l ‐lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double‐emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray‐coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD.     

Thermoplasmonic‐Triggered Release of Loads from DNA‐Modified Hydrogel Microcapsules Functionalized with Au Nanoparticles or Au Nanorods

Microcapsules consisting of hydrogel shells cross‐linked by glucosamine–boronate ester complexes and duplex nucleic acids, loaded with dyes or drugs and functionalized with Au nanoparticles (Au NPs) or Au nanorods (Au NRs), are developed. Irradiation of Au NPs or Au NRs results in the thermoplasmonic heating of the microcapsules, and the dissociation of the nucleic acid cross‐linkers. The separation of duplex nucleic acid cross‐linkers leads to low‐stiffness hydrogel shells, allowing the release of loads. Switching off the light‐induced plasmonic heating results in the regeneration of stiff hydrogel shells protecting the microcapsules, leading to the blockage of release processes. The thermoplasmonic release of tetramethylrhodamine‐dextran, Texas Red‐dextran, doxorubicin‐dextran (DOX‐D), or camptothecin‐carboxymethylcellulose (CPT‐CMC) from the microcapsules is introduced. By loading the microcapsules with two different drugs (DOX‐D and CPT‐CMC), the light‐controlled dose release is demonstrated. Cellular experiments show efficient permeation of Au NPs/DOX‐D or Au NRs/DOX‐D microcapsules into MDA‐MB‐231 cancer cells and inefficient uptake by MCF‐10A epithelial breast cells. Cytotoxicity experiments reveal selective thermoplasmon‐induced cytotoxicity of the microcapsules toward MDA‐MB‐231 cancer cells as compared to MCF‐10A cells. Also, selective cytotoxicity towards MDA‐MB‐231 cancer cells upon irradiation of the Au NPs‐ and Au NRs‐functionalized microcapsules at λ = 532 or 910 nm is demonstrated.     

Controllable Fabrication of Inhomogeneous Microcapsules for Triggered Release by Osmotic Pressure

Inhomogeneous microcapsules that can encapsulate various cargo for controlled release triggered by osmotic shock are designed and reported. The microcapsules are fabricated using a microfluidic approach and the inhomogeneity of shell thickness in the microcapsules can be controlled by tuning the flow rate ratio of the middle phase to the inner phase. This study demonstrates the swelling of these inhomogeneous microcapsules begins at the thinnest part of shell and eventually leads to rupture at the weak spot with a low osmotic pressure. Systematic studies indicate the rupture fraction of these microcapsules increases with increasing inhomogeneity, while the rupture osmotic pressure decreases linearly with increasing inhomogeneity. The inhomogeneous microcapsules are demonstrated to be impermeable to small probe molecules, which enables long‐term storage. Thus, these microcapsules can be used for long‐term storage of enzymes, which can be controllably released through osmotic shock without impairing their biological activity. The study provides a new approach to design effective carriers to encapsulate biomolecules and release them on‐demand upon applying osmotic shock.     

壳聚糖/PHB复合缓释微包囊的制备与体外释药评价

用疏水性聚酯PHB外包覆壳聚糖-三聚磷酸钠-阿斯匹林药物缓释体(CPA)制备了壳聚糖/PHB复合缓释微包囊(CPAB),以克服CPA遇酸不稳定的释药特点.用傅立叶红外分光光度计、激光粒度仪、扫描电镜表征了CPAB的组成、粒径及表面形貌.结果显示,CPAB粒径在50～100nm和载药率18.5%时,表面有不均匀的空隙.体外释药评价证实CPAB能有效解决CPA在酸性下的不稳定性,具有长效缓释作用.     

Release of furosemide from sustained release microcapsules prepared by phase separation technique

Furosemide Eudragit RL-100 sustained release microcapsules were prepared using phase separation technique. The results of the release studies, in sorensen phosphate buffer at PH 7.4, indicated good sustained release of the prepared microcapsules. Increasing drug to polymer ratio resulted in a decrease in the release, while increased release obtained by increasing the PH of the dissolution medium. Dosing of healthy human volunteers with sustained release microcapsules resulted in a reduced and sustained urine volume compared to the profuse diuresis obtained with the conventional furosemide capsules.     

Superhydrophobic Gated Polyorganosilanes/Halloysite Nanocontainers for Sustained Drug Release

Inspired by the water repellency of the lotus leaf, superhydrophobic gated nanocontainers are fabricated by using halloysite nanotubes (HNTs) as the nanocontainers and polyorganosilanes (POS) as the molecular gates for sustained release of diclofenac sodium (DS). The nanocontainers are prepared by loading DS into the lumen of HNTs, and then modified by co‐condensation of hexadecyltriethoxylsilane and tetraethoxysilane. The nanocontainers are characterized with transmission electron microscopy, energy dispersive X‐ray analysis and FTIR, etc. The wetting behaviors of the nanocontainers and release behaviors of DS are also studied. DS molecules are loaded in the lumen of HNTs and POS is covalently bonded on the surface of HNTs‐DS. Wettability of the nanocontainers is controllable simply by the POS content. The nanocontainers show excellent superhydrophobicity with a water contact angle of 156.9° and a water shedding angle of 3°. The release of DS molecules is controlled by a new way, the air cushion between the superhydrophobic nanocontainers and the phosphate buffer solution (PBS). The DS molecules could only release from the limited place where the nanocontainers contact with PBS when the PBS is in the Cassie‐Baxter state on the surface of the nanocontainers.     

Preparation and Characterization of Coacervate Microcapsules for the Delivery of Antimicrobial Oyster Peptides

Oyster peptides-loaded alginate/chitosan/starch microcapsules were prepared using external gelation method and internal emulsion gelation method. The solution of oyster peptides complexes was encapsulated into the microcapsules, which endowed the microcapsules with intestine passive targeting properties. The swelling behavior, encapsulation efficiency, and release behavior of oyster peptides from the microcapsules at different pH values were investigated. The microcapsules exhibited sustained release of the peptides in intestinal medium, and the release rate could be regulated by the pH value: in simulated gastric fluid, the release rate was greatly decreased, and in simulated body fluid and intestinal fluid, the microcapsules exhibited a sustained release in 24 h with different release rates. The microspheres were characterized by Fourier transform infrared. The results suggested that the alginate/chitosan/starch microcapsules could be a suitable copolymeric carrier system for intestinal protein or peptides delivery in the intestine.     

Preparation and characterization of coacervate microcapsules for the delivery of antimicrobial oyster peptides

Oyster peptides-loaded alginate/chitosan/starch microcapsules were prepared using external gelation method and internal emulsion gelation method. The solution of oyster peptides complexes was encapsulated into the microcapsules, which endowed the microcapsules with intestine passive targeting properties. The swelling behavior, encapsulation efficiency, and release behavior of oyster peptides from the microcapsules at different pH values were investigated. The microcapsules exhibited sustained release of the peptides in intestinal medium, and the release rate could be regulated by the pH value: in simulated gastric fluid, the release rate was greatly decreased, and in simulated body fluid and intestinal fluid, the microcapsules exhibited a sustained release in 24 h with different release rates. The microspheres were characterized by Fourier transform infrared. The results suggested that the alginate/chitosan/starch microcapsules could be a suitable copolymeric carrier system for intestinal protein or peptides delivery in the intestine.     

Concurrent Drug Unplugging and Permeabilization of Polyprodrug‐Gated Crosslinked Vesicles for Cancer Combination Chemotherapy

Combination chemotherapy with both hydrophobic and hydrophilic therapeutic drugs is clinically vital toward the treatment of persistent cancers. Though conventional liposomes and polymeric vesicles possessing hydrophobic bilayers and aqueous interiors can serve as codelivery nanocarriers, it remains a considerable challenge to achieve synchronized release of both types of drugs due to distinct encapsulation mechanisms; premature release of water‐soluble cargos from unstable liposomes and ruptured vesicles is also a major concern. Herein, the fabrication of physiologically stable polyprodrug‐gated crosslinked vesicles (GCVs) via the self‐assembly of camptothecin (CPT) polyprodrug amphiphiles and in situ bilayer crosslinking through traceless sol–gel reaction is reported. Polyprodrug‐GCVs possess high CPT loading (>30 wt%) and minimized leakage of encapsulated hydrophilic doxorubicin (DOX) hydrochloride due to the suppressed permeability of crosslinked membrane, exhibiting extended blood circulation (t _1/2 > 13 h) with caged cytotoxicity in physiological circulation. Upon cellular uptake by cancer cells, cytosolic reductive milieu‐triggered CPT unplugging from vesicle bilayers is demonstrated to generate hydrophilic mesh channels and make the membrane highly permeable. Concurrently, it will promote DOX corelease from hydrophilic lumen (≈36‐fold increase). The reduction‐activated combination chemotherapeutic potency based on polyprodrug‐GCVs is confirmed by both in vitro and in vivo explorations.     

双乳液体系在微胶囊制备中的应用研究进展

双乳液是一类多重乳状液体系,它具有保护物质并且可以控制这些物质从一个相释放到另一个相的能力。近年来这类乳液体系与传统微胶囊制备方法的结合在药物输送(如抗癌药物、激素等)、食品等领域得到了一定的应用,解决了传统微胶囊制备方法无法有效封装高度水溶性物质等问题。基于此,综述了双乳液体系与微胶囊制备方法结合延伸出的一些新方法,包括双乳液-复凝聚法、复乳溶剂挥发法以及膜乳化复乳法等;同时,评述了影响双乳液体系制备微胶囊的各种因素,展望了双乳液体系在农药微胶囊制备中的应用前景。     

Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N₂ adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m²/g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties.     

Perforated Bicontinuous Cubic Phases with pH‐Responsive Topological Channel Interconnectivity

Lipidic lyotropic liquid crystals are at the frontline of current research for release of target therapeutic molecules due to their unique structural complexity and the possibility of engineering stimuli‐triggered release of both hydrophilic and hydrophobic molecules. One of the most suitable lipidic mesophases for the encapsulation and delivery of drugs is the reversed double diamond bicontinuous cubic phase, in which two distinct and parallel networks of ～4 nm water channels percolate independently through the lipid bilayers, following a Pn3m space group symmetry. In the unperturbed Pn3m structure, the two sets of channels act as autonomous and non‐communicating 3D transport pathways. Here, a novel type of bicontinuous cubic phase is introduced, where the presence of OmpF membrane proteins at the bilayers provides unique topological interconnectivities among the two distinct sets of water channels, enabling molecular active gating among them. By a combination of small‐angle X‐ray scattering, release and ion conductivity experiments, it is shown that, without altering the Pn3m space group symmetry or the water channel diameter, the newly designed perforated bicontinuous cubic phase attains transport properties well beyond those of the standard mesophase, allowing faster, sustained release of bioactive target molecules. By further exploiting the pH‐mediated pore‐closing response mechanism of the double amino acid half‐ring architecture in the membrane protein, the pores of the perforated mesophase can be opened and closed with a pH trigger, enabling a fine modulation of the transport properties by only moderate changes in pH, which could open unexplored opportunities in the targeted delivery of bioactive compounds.     

Biocompatible Smart Microcapsules Based on Chitosan‐Poly(vinyl alcohol) Copolymers for Cultivation of Animal Cells

In this study, two novel chitosan‐graft‐poly(vinyl alcohol) copolymers are synthesized and used as water‐soluble at physiological conditions polycations for preparation of smart microcapsules. The microcapsules provide growth and proliferation of eight mammalian cell lines, including hybridoma and tumor cells, at long‐term cell cultivation in vitro. The microcapsules are stable in cell culture medium but can be dissolved by changing pH value of the medium (up to 8.0–8.2), thus making possible a simple release of the entrapped cells. Monoclonal antibody production by encapsulated hybridoma cells is demonstrated. Cultivation of tumor cells within the microcapsules allows the formation of 3D multicellular spheroids, which can be proposed as an in vitro model for anticancer drug screening.     

异噻唑啉酮微胶囊的制备表征及释放行为

以二异氰酸酯(TDI)、聚乙二醇4000(PEG)、二羟甲基丙酸(DMPA)和三乙胺(TEA)为原料,制备可水乳化的聚氨酯(WPU).以合成的WPU为囊壁、以异噻唑啉酮衍生物(Sea-nine 211)为囊芯,通过乳化自组装得到防污剂Sea-nine 211微胶囊,用红外光谱、粒径分布和扫描电镜对胶囊进行表征,并采用分...     

聚氨基酸复合微胶囊对Hb的控制释放

以生物相容性好、价格低廉的海藻酸钠(ALG)为聚阴离子芯材,通过静电液滴装置制备了平均粒径在290 μm左右、球形度好、表面光洁的海藻酸钙胶珠;再将生物可降解、具有介入治疗作用的聚精氨酸(PLA)与聚组氨酸(PLH)的混合物作为聚阳离子壁材,在海藻酸钙胶珠表面覆上一层高分子聚合膜以制备聚氨基酸复合微胶囊;并以牛血红蛋白Hb为药物模型,对微胶囊的控制释放性能进行了考察并将其初步应用于体外模拟口服给药。结果表明:聚氨基酸复合微胶囊在前0.5 h的累积释放量均低于40％,溶出结束时累积释放量均达到80%以上;ALG/(PLA-PLH)复合微胶囊和ALG/PLH微胶囊的药物释放速率均低于ALG/PLA微胶囊;于10 min成膜时间内制备的微胶囊具有较高的载药量、包封率和缓释性能;以pH 4.6 HAc-NaAc缓冲液为成膜溶媒制备的微胶囊,Hb持续释放时间和残留量均高于蒸馏水组;前2 h在模拟胃液的pH 1.2 HCl溶媒中累计释放的Hb不超过10％且绝大部分是在模拟肠液环境即pH 6.8 PBS 溶媒中释放的;壳聚糖的引入能在一定程度上延长药物释放时间。聚氨基酸复合微胶囊具备一定的缓释性、pH响应性和生理黏附性,有望成为一种口服给药系统用药物载体。      

疏水改性海藻酸钠衍生物包埋丁香油的释放性

目的通过化学方法将月桂醇与海藻酸钠接枝共聚形成两亲共聚物,对丁香油进行包埋形成微胶囊,使其具有一定的缓释性和良好的抗菌效果。方法利用两亲共聚物包埋丁香油形成包合物,采用单因素实验法,以包埋率为指标,评价月桂醇与海藻酸的接枝率对包埋率的影响,并在此基础上评价接枝率对缓释性以及不同环境下的稳定性和抗菌性能。结果在一定范围内包埋率随着接枝率的增大而升高;丁香油微胶囊的挥发率为14.11%,远低于丁香油的挥发率61.25%;释放试验中,丁香油微胶囊的缓释性明显优于未改性海藻酸纳,丁香油微胶囊能稳定缓慢地释放抗菌成分,控制大肠杆菌的生长。结论月桂醇改性海藻酸钠包埋丁香油形成的微胶囊具有一定的缓释和抗菌性能,突破了丁香油因挥发性强而存在的应用限制。     

Bioinspired Viscoelastic Capsules: Delivery Vehicles and Beyond

Microcapsules are often used as individually dispersed carriers of active ingredients to prolong their shelf life or to protect premature reactions with substances contained in the surrounding. This study goes beyond this application and employs microcapsules as principal building blocks of macroscopic 3D materials with well‐defined granular structures. To achieve this goal and inspired by nature, capsules are fabricated from block‐copolymer surfactants that are functionalized with catechols, a metal‐coordinating motive. These surfactants self‐assemble at the surface of emulsion drops where they are ionically cross‐linked to form viscoelastic capsules that display a low permeability even toward small encapsulants. It is demonstrated that the combination of the mechanical strength, flexibility, and stickiness of the capsules enables their additive manufacturing into macroscopic granular structures. Thereby, they open up new opportunities for 3D printing of soft, self‐healing materials composed of individual compartments that can be functionalized with different types of spatially separated reagents.     

Release of Theophylline from Ethyl Cellulose Mecrocapsues Alone and in Conjuction with Fat Embedded (Precirol®) Granules and Hydroxypropyl Methycellulose

Abstract

Microcapsules of theophylline with ethyl cellulose were prepared by coacervation technique using cabosil® (silicon dioxide) as separant. Tablets were prepared from microcapsules, microcapsules + theophylline fat embedded granules, and microcapsules and hydroxypropyl methylcellulose 4000 (HPMC). Release was studied in vitro by the rotating basket method. Prolonged release of theophylline was observed from microcapsules with no drug dumping. The release from microcapsules was of first-order whereas that from all the tablet formulation was diffusion controlled according to the Higuchi model. Good correlation was found between release rate and core:wall ratio for all the systems. Decrease in hardness of tablets made from microcapsules alone decreased the release rate, indicating damage of microcapsules during compression. The tablets compressed from fat embedded granules, microcapsules with fat embedded granules, and microcapsules with HPMC gave a desired release for a 74 hour sustained release preparation.     

Polymersomes Containing a Hydrogel Network for High Stability and Controlled Release

Capillary microfluidic devices are used to prepare monodisperse polymersomes consisting of a hydrogel core and a bilayer membrane of amphiphilic diblock‐copolymers. To make polymersomes, water‐in‐oil‐in‐water double‐emulsion drops are prepared as templates through single‐step emulsification in a capillary microfluidic device. The amphiphile‐laden middle oil phase of the double‐emulsion drop dewets from the surface of the innermost water drop, which contains hydrogel prepolymers; this dewetting leads to the formation of a bilayer membrane. Subsequently, the oil phase completely separates from the innermost water drop, leaving a polymersome. Upon UV illumination of the polymersome, the prepolymers encapsulated within the interior are crosslinked, forming a hydrogel core. The hydrogel network within the polymersomes facilitates sustained release of the encapsulated materials and increases the stability of the polymersomes through the formation of a scaffold to support the bilayer. In addition, this approach provides a facile method to make monodisperse hydrogel particles directly dispersed in water.