Biodegradable Hydrophobic Injectable Polymers for Drug Delivery and Regenerative Medicine

Biodegradable, hydrophobic, and injectable liquid polymers are capable of achieving the minimally invasive, sustained, and local release of drugs. These hydrophobic injectable polymers also have potential in the area of regenerative medicine where the biomaterial should be stable for a certain period and then degrade to allow the growth of cells/tissues. This review presents exclusive coverage of biocompatible hydrophobic injectable pasty or liquid polymers that can be injected without the use of any solvent for drug delivery, tissue augmentation, and regenerative medicine application. The synthesis methodologies of several major types of hydrophobic pasty polymers used in the biomedical fields and their properties with the foremost criteria to serve as injectable biomaterial for localized drug delivery and regenerative medicine is described. The hydrophobic biodegradable injectable polymers discussed are aliphatic polyesters, polycarbonates and polyanhydrides, prepared from: lactic acid, glycolic acid, caprolactone, aliphatic diols and diacids, hydroxy fatty acids, and triglycerides such as castor oil.     

Compressible and Electrically Conducting Fibers for Large‐Area Sensing of Pressures

Flexible pressure sensors offer a wide application range in health monitoring and human–machine interaction. However, their implementation in functional textiles and wearable electronics is limited because existing devices are usually small, 0D elements, and pressure localization is only achieved through arrays of numerous sensors. Fiber‐based solutions are easier to integrate and electrically address, yet still suffer from limited performance and functionality. An asymmetric cross‐sectional design of compressible multimaterial fibers is demonstrated for the detection, quantification, and localization of kPa‐scale pressures over m²‐size surfaces. The scalable thermal drawing technique is employed to coprocess polymer composite electrodes within a soft thermoplastic elastomer support into long fibers with customizable architectures. Thanks to advanced mechanical analysis, the fiber microstructure can be tailored to respond in a predictable and reversible fashion to different pressure ranges and locations. The functionalization of large, flexible surfaces with the 1D sensors is demonstrated by measuring pressures on a gymnastic mat for the monitoring of body position, posture, and motion.     

MPOF的制备

微结构聚合物光纤(MPOF)是一种新型的光纤,有着良好的应用前景,为此介绍了MPOF的各种制备方法:毛细管堆叠法、铸塑法、钻孔法等;并用毛细管堆叠法和铸塑法分别制作了一种微结构双折射光纤和一种分段式包层结构光纤.还提出了一些具有创新意义的工艺手段,而这些工艺手段通过实验证明是令人满意的.     

Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery

The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA‐loaded nanogels can be internalized by HuH‐7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza‐derived fusogenic peptide (diINF‐7) can significantly improve the silencing efficiency of siRNA‐loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA.     

Fabrication and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow Fibers

Ultrathin mesoporous bioactive glass hollow fibers (MBGHFs) fabricated using an electrospinning technique and combined with a phase‐separation‐induced agent, poly(ethylene oxide) (PEO), are described. The rapid solvent evaporation during electrospinning and the PEO‐induced phase separation process demonstrated play vital roles in the formation of ultrathin bioactive glass fibers with hollow cores and mesoporous walls. Immersing the MBGHFs in simulated body fluid rapidly results in the development of a layer of enamel‐like apatite mesocrystals at the fiber surfaces and apatite nanocrystals inside the hollow cores. Drug loading and release experiments indicate that the drug loading capacity and drug release behavior of the MBGHFs strongly depends on the fiber length. MBGHFs with fiber length >50 µm can become excellent carriers for drug delivery. The shortening of the fiber length reduces drug loading amounts and accelerates drug release. The MBGHFs reported here with sophisticated structure, high bioactivity, and good drug delivery capability can be a promising scaffold for hard tissue repair and wound healing when organized into 3D macroporous membranes.     

Superhydrophobic,Reversibly Elastic,Moldable, and Electrospun (SupREME) Fibers with Multimodal Functions: From Oil Absorbents to Local Drug Delivery Adjuvants

Surface hydrophobicity has served as a core means for governing the spatial behaviors of numerous substances depending on their affinities to oil or aqueous phases. Exploiting systems that can maximize hydrophobic features contributes to the development of versatile supports capable of spatially separating, guiding, or protecting target materials in defined manners. Herein, superhydrophobic, reversibly elastic, moldable, and electrospun (SupREME) fibers, which exhibit multimodal functions for arranging spatial responses of substances with distinct affinities to oil phases, are fabricated by coaxially electrospinning polysulfone and poly(glycerol sebacate) (PGS), followed by a thermal process. The exterior PSF layers enable volumetric expansion of the fibers, further reinforcing the overall superhydrophobicity (contact angles >150°). The elastic core PGS networks confer reversibly compressible properties (>100 cycles) to the fibers, ultimately enhancing their hydrophobic performance and extending their durability. The SupREME fibers demonstrate superiorities as absorbents for selectively separating oil‐based substances, sealants for blocking the leakage of aqueous fluids, and adjuvants for temporarily enhancing the local residence of drugs by repelling ambient fluidic environments. The SupREME fibers can be versatile platforms in many applications that require the spatial regulation of specific substances with affinities to oil or water phases, ranging from environmental industries to medical fields.     

Ultrafast Electrochemical Trigger Drug Delivery Mechanism for Nanographene Micromachines

Nano/micromachines with autonomous motion are the frontier of nanotechnology and nanomaterial research. These self‐propelled nano/micromachines convert chemical energy obtained from their surroundings to propulsion. They have shown great potential in diagnostic and therapeutic applications. This work introduces a high‐speed tubular electrically conductive micromachine based on reduced nanographene oxide (n‐rGO) as a platform for drug delivery and platinum (Pt) as the catalytic inner layer. n‐rGO/Pt micromachines are loaded with doxorubicin (DOX) by a simple physical adsorption with a very high loading efficiency, displaying single‐ or multistrand wrapping of DOX monomers on the micromachine cylinders. More importantly, it is found that electron injection into DOX@n‐rGO/Pt micromachines via electrochemistry leads to expulsion of DOX from micromachines in motion within only a few seconds. An in vitro study confirms this efficient release mechanism in the presence of cancerous cells. The unique properties of the n‐rGO/Pt micromotor enable the effective management of DOX release at the tumor site and thus enhances the therapeutic efficiency and reduces the side toxicity toward the healthy tissue. These micromachine drug carriers combine the high loading capacity of conventional carbon‐based drug carriers with a fast and efficient electrochemical drug‐release mechanism.     

Up‐Conversion Luminescent and Porous NaYF4:Yb3+, Er3+@SiO2 Nanocomposite Fibers for Anti‐Cancer Drug Delivery and Cell Imaging

Up‐conversion (UC) luminescent and porous NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers are prepared by electrospinning process. The biocompatibility test on L929 fibrolast cells reveals low cytotoxicity of the fibers. The obtained fibers can be used as anti‐cancer drug delivery host carriers for investigation of the drug storage/release properties. Doxorubicin hydrochloride (DOX), a typical anticancer drug, is introduced into NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers (denoted as DOX‐NaYF₄:Yb³⁺, Er³⁺@SiO₂). The release properties of the drug carrier system are examined and the in vitro cytotoxicity and cell uptake behavior of these NaYF₄:Yb³⁺, Er³⁺@SiO₂ for HeLa cells are evaluated. The release of DOX from NaYF₄:Yb³⁺, Er³⁺@SiO₂ exhibits sustained, pH‐sensitive release patterns and the DOX‐NaYF₄:Yb³⁺, Er³⁺@SiO₂ show similar cytotoxicity as the free DOX on HeLa cells. Confocal microscopy observations show that the composites can be effectively taken up by HeLa cells. Furthermore, the fibers show near‐infrared UC luminescence and are successfully applied in bioimaging of HeLa cells. The results indicate the promise of using NaYF₄:Yb³⁺, Er³⁺@SiO₂ nanocomposite fibers as multi‐functional drug carriers for drug delivery and cell imaging.     

Charge‐Reversal Drug Conjugate for Targeted Cancer Cell Nuclear Drug Delivery

DNA‐toxin anticancer drugs target nuclear DNA or its associated enzymes to elicit their pharmaceutical effects, but cancer cells have not only membrane‐associated but also many intracellular drug‐resistance mechanisms that limit their nuclear localization. Thus, delivering such drugs directly to the nucleus would bypass the drug‐resistance barriers. The cationic polymer poly(L ‐lysine) (PLL) is capable of nuclear localization and may be used as a drug carrier for nuclear drug delivery, but its cationic charges make it toxic and cause problems in in‐vivo applications. Herein, PLL is used to demonstrate a pH‐triggered charge‐reversal carrier to solve this problem. PLL's primary amines are amidized as acid‐labile β‐carboxylic amides (PLL/amide). The negatively charged PLL/amide has a very low toxicity and low interaction with cells and, therefore, may be used in vivo. But once in cancer cells' acidic lysosomes, the acid‐labile amides hydrolyze into primary amines. The regenerated PLL escapes from the lysosomes and traverses into the nucleus. A cancer‐cell targeted nuclear‐localization polymer–drug conjugate has, thereby, been developed by introducing folic‐acid targeting groups and an anticancer drug camptothecin (CPT) to PLL/amide (FA‐PLL/amide‐CPT). The conjugate efficiently enters folate‐receptor overexpressing cancer cells and traverses to their nuclei. The CPT conjugated to the carrier by intracellular cleavable disulfide bonds shows much improved cytotoxicity.     

Nanogel Encapsulated Hydrogels As Advanced Wound Dressings for the Controlled Delivery of Antibiotics

Biocompatible and degradable dual-delivery gel systems based on hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualized and accomplished via thiol-ene click chemistry. The elasticity of the hydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dry weight percentages (20, 30, 40 wt%), and are found to range from 2–14.7 kPa, comparable to human skin. The co-delivery of antibiotics is achieved, where the hydrophilic drug novobiocin sodium salt (NB) is entrapped within the hydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) is encapsulated within the dendritic nanogels (DNGs) with hydrophobic cores (DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are then physically entrapped within the hybrid hydrogels through UV curing. The hybrid hydrogels enable the quick release of NB and prolonged released of CIP. In vitro cell infection assays showed that the antibiotic-loaded hybrid hydrogels are able to treat bacterial infections with significant bacterial reduction. Hybrid hydrogel band aids are fabricated and exhibited better antibacterial activity compared with commercial antimicrobial band aids. Remarkably, most hydrogels and hybrid hydrogels show enhanced human dermal cell proliferation and could be degraded into non-toxic constituents, showing great promise as wound dressing materials.     

Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination

Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, a microneedle materials platform is demonstrated for rapid implantation of controlled‐release polymer depots into the cutaneous tissue. Arrays of microneedles composed of drug‐loaded poly(lactide‐co‐glycolide) (PLGA) microparticles or solid PLGA tips are prepared with a supporting and rapidly water‐soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforate the stratum corneum and epidermis. Penetration of the outer skin layers is followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which are retained following patch removal. These polymer depots remain in the skin for weeks following application and sustain the release of encapsulated cargos for systemic delivery. To show the utility of this approach the ability of these composite microneedle arrays to deliver a subunit vaccine formulation is demonstrated. In comparison to traditional needle‐based vaccination, microneedle delivery gives improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.     

Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino‐β‐cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β‐cyclodextrin/adamantane complexation. The non‐cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate‐receptor‐rich HeLa cancer cells through receptormmediated endocytosis, while folate‐receptor‐poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β‐cyclodextrin capping rings by cleaving the pre‐installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug‐delivery efficacy of the multifunctional nanoparticles is attributed to the co‐operative effects of folate‐mediated targeting and stimuli‐triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.     

Recent Advancements and Perspectives of Biodegradable Polymers for Supercapacitors

Supercapacitors (SCs) have demonstrated great potential for integration into future wearable and implantable electronics, yet the insufficient environmental adaption and biosafety limit their further development. To this regard, application of biodegradable polymers is considered as an ideal solution strategy for the environmentally sound disposal of SCs. The biodegradable polymers with satisfactory degradability and excellent biocompatibility demonstrate an irreplaceable role in the future development of SCs and provide an ideal solution strategy for its environmentally sound disposal. In this review, the research progress and challenges of biodegradable polymers in the field of SCs are discussed and analyzed. First, the classification of existing biodegradable polymers and their typical structure, properties, and preparation processes are elucidated. Subsequently, the main applications of biodegradable polymers in different components of SCs, including electrodes, electrolytes, substrate, and encapsulation materials, are summarized. In addition, the research progress of biodegradable polymer-based SCs in terms of preparation strategies and modification methods is summarized, and the key role of biodegradable polymers in the development process of green SCs is deeply discussed. Finally, the future perspectives and challenges faced by the biodegradable polymer-based SCs are briefly proposed.     

Self‐Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation,Release and In Vitro Delivery

The self‐assembling peptide EAK16‐II is capable of stabilizing hydrophobic compounds to form microcrystal suspensions in aqueous solution. Here, the ability of this peptide to stabilize the hydrophobic anticancer agent ellipticine is investigated. The formation of peptide‐ellipticine suspensions is monitored with time until equilibrium is reached. The equilibration time is found to be dependent on the peptide concentration. When the peptide concentration is close to its critical aggregation concentration, the equilibration time is minimal at 5 h. With different combinations of EAK16‐II and ellipticine concentrations, two molecular states (protonated or cyrstalline) of ellipticine could be stabilized. These different states of ellipticine significantly affect the release kinetics of ellipticine from the peptide‐ellipticine complex into the egg phosphatidylcholine vesicles, which are used to mimic cell membranes. The transfer rate of protonated ellipticine from the complex to the vesicles is much faster than that of crystalline ellipticine. This observation may also be related to the size of the resulting complexes as revealed from the scanning electron micrographs. In addition, the complexes with protonated ellipticine are found to have a better anticancer activity against two cancer cell lines, A549 and MCF‐7. This work forms the basis for studies of the peptide‐ellipticine suspensions in vitro and in vivo leading to future development of self‐assembling peptide‐based delivery of hydrophobic anticancer drugs.     

Microfabricated Drug Delivery Devices: Design,Fabrication, and Applications

Microfabrication technology has enabled the development of novel controlled‐release devices that possess an integration of structural, mechanical, and perhaps electronic features, which may address challenges associated with conventional delivery systems. In this feature article, microfabricated devices are described in terms of materials, mechanical design, working principles, and fabrication methods, all of which are key features for production of multifunctional, highly effective drug delivery systems. In addition, the current status and future prospects of different types of microfabricated devices for controlled drug delivery are summarized and analyzed with an emphasis on various routes of administration including ocular, oral, transdermal, and implantable systems. It is likely that microfabrication technology will continue to offer new, alternative solutions to design advanced and sophisticated drug delivery devices that promise to significantly improve medical care.     

Tumor Acidity and Near-Infrared Light Responsive Dual Drug Delivery Polydopamine-Based Nanoparticles for Chemo-Photothermal Therapy

Photothermal therapy (PTT) combined with chemotherapy, a promising strategy for breast cancer treatment, has a high potential to control drug release, reduce multidrug resistance, and improve therapeutic efficacy. The challenge is how to realize tumor ablation in deeper tissue and NIR-controlled drug delivery. Herein, tumor acidity and near-infrared light (NIR) responsive folic acid (FA) functionalized polydopamine (DPA) nanoparticles (NPs) are developed for doxorubicin (DOX) and epigallocatechin-3-gallate (EGCG) dual delivery. With the assistance of NIR, the cellular uptake of DOX-EGCG/DPA-FA NPs is about three- to sixfold higher when compared with the free DOX group and the control group without NIR irradiation. Moreover, biodistribution study in vivo indicates that DPA-FA NPs can enhance tumoral accumulation, penetration, retention of drugs, and display a ≈ 4- and 19-fold higher intra-tumoral distribution than that of the DPA NPs and free drug groups at 24 h postinjection. Furthermore, 60% of breast cancer-bearing mice survive over 70 days in the DOX-EGCG/DPA-FA NPs group. Additionally, DOX-EGCG/DPA-FA NPs can effectively boost therapeutic efficacy by inducing significant suppression of tumor growth and angiogenesis, and enhancement of apoptosis and necrosis of breast cancer cells. Taken together, DOX-EGCG/DPA-FA NPs may have potential applications as a useful nanoscale vector for enhanced cancer therapy.     

用于药物释放系统的柔性微针研制

提出了一种基于MEMS技术在柔性基底上制造微针的工艺技术,这是一种高效、安全和无痛的全新给药方式-微针阵列.该微针阵列能够适用于平面或非平面物体表面,对大分子药剂、蛋白质或者疫苗合成药剂也能够使用.     

Synthesis and Characterization of Positive‐Charge Functionalized Mesoporous Silica Nanoparticles for Oral Drug Delivery of an Anti‐Inflammatory Drug

We synthesized mesoporous silica nanoparticles (MSN) with different densities of surface positive charges. The positive surface charge was generated by incorporating trimethylammonium (TA) functional groups into the framework of MSN (MSN–TA) via direct co‐condensation of a TA‐silane and tetraethoxysilane (TEOS) in the presence of a base as a catalyst. These MSN–TA samples have well‐defined hexagonal structures with an average particle diameter of 100 nm, pore size of 2.7 nm, and surface area of about 1000 m² g^?1. Anionic drug molecules, Orange II (a fluorescent tracing molecule), and sulfasalazine (an anti‐inflammatory prodrug used for bowel disease), were effectively loaded into these MSN–TA samples and remained inside of the MSN–TA under acidic environment (pH 2–5). The amounts of loading of both Orange II and sulfasalazine were increased with increasing positive charge densities resulting from the increasing number of TA groups. When these drug‐loaded MSN–TA nanoparticles were placed in physiological buffer solution (pH 7.4), a partial negative surface charge on the MSN–TA was generated due to the deprotonation of silanol groups, and the strong electrostatic repulsion triggered a sustained release of the loaded molecules. MSN–TA as a nanovehicle for pH‐dependent loading and controllable release of anionic drug molecules can be used as an oral delivery drug systems targeting at intestine. These drugs can be remained trapped in the nanovehicle when passing through the stomach's acidic environment and be released in intestine where the environmental pH is close to neutral.