Oral delivery is one of the facile methods for the administration of active ingredients (AIs) like nutraceuticals and drugs. However, its intrinsic disadvantages include poor absorption and bioavailability, degradation of the AI during transit through the gastrointestinal tract (GIT), and a lack of action specificity. Hence, a delivery system for targeted gastrointestinal delivery of AI using polysaccharide‐based polymers, that are generally recognized as safe and approved for use as a direct food additive, is proposed. In this regard, mucoadhesive chitosan nanoparticles that could adhere to the mucosa of the GIT are fabricated and encapsulated with AI. These particles are subsequently coated with polysaccharides that have different enzymatic susceptibilities, to allow for specific degradation in the small or large intestines. It is observed that the polysaccharide coating efficiently retarded the nonspecific release of the encapsulated agent until it is exposed to its intended environment of release. The cytotoxicity and uptake of chitosan nanoparticles is further evaluated on Caco2 cells. In conclusion, these polysaccharide‐coated nanoparticles can potentially be targeted to different organs in the GIT and to be taken up by the enterocytes for improved oral bioavailability. 相似文献
Complementary nucleobase‐functionalized polymeric micelles, a combination of adenine‐thymine (A‐U) base pairs and a blend of hydrophilic–hydrophobic polymer pairs, can be used to construct 3D supramolecular polymer networks; these micelles exhibit excellent self‐assembly ability in aqueous solution, rapid pH‐responsiveness, high drug loading capacity, and triggerable drug release. In this study, a multi‐uracil functionalized poly(ε‐caprolactone) (U‐PCL) and adenine end‐capped difunctional oligomeric poly(ethylene glycol) (BA‐PEG) are successfully developed and show high affinity and specific recognition in solution owing to dynamically reversible A‐U‐induced formation of physical cross‐links. The U‐PCL/BA‐PEG blend system produces supramolecular micelles that can be readily adjusted to provide the desired critical micellization concentration, particle size, and stability. Importantly, in vitro release studies show that doxorubicin (DOX)‐loaded micelles exhibit excellent DOX‐encapsulated stability under physiological conditions. When the pH value of the solution is reduced from 7.4 to 5.0, DOX‐loaded micelles can be rapidly triggered to release encapsulated DOX, suggesting these polymeric micelles represent promising candidate pH‐responsive nanocarriers for controlled‐release drug delivery and pharmaceutical applications.
Recently three groups of rifampicin (RIF)-loaded microparticles (MPs), consisting of chitosan (CHT), PLGA and PLGA/CHT mixtures, were assessed in terms of RIF-loading and retention during nebulisation. The CHT-coated PLGA MPs were found to exhibit high RIF-loading ability together with nebulisation ability, stability, and mucoadhesive properties. All MP types had comparable toxicity towards alveolar cells which was significantly lower than that of the free drug. Herein, we study the release of RIF from all MP-types, during incubation in buffer with pH values: 4.40 and 7.40. Results show that CHT particles exhibit a higher burst release compared to PLGA MPs; at pH 4.40, which is explained by the higher solubility of CHT in acidic media. At pH 7.40 burst release from CHT MP's is significantly lower when CHT is crosslinked with glutaraldehyde, which is consistent with their - previously observed - increased stability during nebulization. From PLGA MPs, RIF release was pH independent under the conditions applied, while the amount of PVA (stabilizer) considerably affected drug release. When PLGA MP's were coated with CHT, at pH 7.40 the retention of RIF increased further (compared to non-coated MPs), while at pH 4.40 the release was faster from the CHT-coated particles. Concluding, it is proven that when PLGA MPs are coated with CHT, in addition to increased particle mucoadhesive properties, the release kinetics of RIF are modified. 相似文献
Stimuli‐responsive microcontainers have become a major topic of interest, from fundamental aspects to applications in materials science. However, microcontainers that enable the loading of multiple species and programmable release are mostly unexplored. Herein, we describe the design and synthesis of a dual‐responsive organic/inorganic hybrid microcontainer with two payloads in separate storage spaces that is formed by the rapid UV‐initiated polymerization of Pickering emulsions. The stellate mesopore silica nanoparticles with poly(N ‐isopropylacrylamide) grafted inside the mesopores were loaded with one compound (Nile red) and used as Pickering emulsifiers to stabilize oil‐in‐water droplets. Upon UV irradiation, pH‐responsive monomers were polymerized in the presence of 5(6)‐carboxyfluorescein diacetate (CFDA) to form hybrid colloidal microcontainers. The release of Nile red and CFDA could be selectively activated by changing the temperature or pH value. 相似文献
Doxorubicin(DOX) loaded poly(lactic-co-glycolic acid)(PLGA) microparticles with internal pores(MP-D) were developed for long-acting release in pulmonary inhalation treatment. The PLGA microparticles exhibited favorable aerodynamic properties for pulmonary delivery. In vitro drug release profile suggested that MP-D have the advantage of long-term maintenance of drug concentrations. MTT assay demonstrated the in vitro anti-tumor efficiency of the DOX loaded PLGA microparticles. Furthermore, melanoma lung metastasis model was established to determine the in vivo antitumor efficiency. The mice treated with MP-D showed significantly fewer lesions than the untreated ones. The survival analysis indicated that MP-D prolonged the survival time of tumor-bearing mice. These results suggested that DOX loaded PLGA microparticles with internal pores have the potential to be used as long-acting release carriers in clinical lung cancer treatment. 相似文献
The development of thermo‐responsive and reduction‐sensitive polymeric micelles based on an amphiphilic block copolymer poly[(PEG‐MEMA)‐co‐(Boc‐Cyst‐MMAm)]‐block‐PEG (denoted PEG‐P‐SS‐HP) for the intracellular delivery of anticancer drugs is reported. PTX, as model drug, was loaded into the PEG‐P‐SS‐HP micelles with an encapsulation efficiency >90%, resulting in a high drug loading content (up to 35 wt%). The PTX‐loaded PEG‐P‐SS‐HP micelles show slow drug release in PBS and rapid release after incubation with DTT. The PTX‐loaded micelles display a better cytotoxic effect than the free drug, whereas empty micelles are found to be non‐toxic. The thermo‐responsive and reduction‐sensitive polymeric micelles described may serve as promising carriers for cytostatic drugs.
New mucoadhesive formulations were designed and studied in order to improve local vaginal therapy by increasing formulation retention prolonging thus drug-mucosa contact time. Some gels were prepared using hydroxyethylcellulose (HEC) alone or mixed with chitosan (CS) or its derivative 5-methyl-pyrrolidinone-chitosan (MPCS) and were loaded with the antibacterial metronidazole (MET) (0.75%). All formulations showed pseudoplastic flow and viscosity increase was observed proportionally to chitosan content (CS>MPCS). Prepared gels showed better extrusion properties (yield stress) than market formulation Zidoval. Mucoadhesion force studies permitted to point out that: (i) CS decreases mucoadhesion force; (ii) MPCS addition increases the mucoadhesion force at high percentage; (iii) all gels containing chitosan showed better mucoadhesive performances than Zidoval. Gels containing MPCS showed higher and faster drug release than those containing CS. All the preparations were able to release higher drug amounts if compared to market formulation. In conclusion MPCS improved gel characteristics in terms of mucoadhesion force, rheological behaviour and drug release pointing out that this modified chitosan is very suitable to obtain manageable and more acceptable vaginal formulation. 相似文献
Colon-targeted delivery devices based on methacrylic functionalized Tween monomer networks, useful for 5-FU or Ferulic acid site-specific release, were synthesized. The basic design consists of methacrylic functionalized Tween monomer-based networks prepared with or without acrylic acid as co-monomer. The swelling behaviour and loaded drugs release from these gels was studied as a function of pH. The devices showed a strong pH-dependent swelling behaviour, allowing a maximum release at pH 7.4. The acrylic acid introduction increased the polymeric gels pores size, as evidenced by the loading efficiency increase, but also reduced the amount of released drug in basic media compared to analogous network not containing the co-monomer. This behaviour, already found in the matrix swelling, could be attributed to a slower hydrolysis kinetics of the ester bond in functionalized Tween monomers, which implies a reduced ability to absorb water from a basic medium, resulting in a lower capacity to release the loaded drug.Since our device possesses a maximum drug release in the media at pH 7.4, it could be used for colon-targeted drug delivery of both 5-FU and Ferulic acid. 相似文献
Thermally sensitive polymeric nanocarriers were developed to optimize the release profile of encapsulated compounds to improve treatment efficiency. However, when referring to thermally sensitive polymeric nanocarriers, this usually means systems fabricated from lower critical solution temperature (LCST) polymers, which have been intensively studied. To extend the field of thermally sensitive polymeric nanocarriers, we for the first time fabricated a polymeric drug delivery system having an upper critical solution temperature (UCST) of 43 °C based on an amphiphilic polymer poly(AAm‐co‐AN)‐g‐PEG. The resulting polymeric micelles could effectively encapsulate doxorubicin and exhibited thermally sensitive drug release both in vitro and in vivo. A drastically improved anticancer efficiency (IC50 decreased from 4.6 to 1.6 μg mL?1, tumor inhibition rate increased from 55.6 % to 92.8 %) was observed. These results suggest that UCST‐based drug delivery can be an alternative to thermally sensitive LCST‐based drug delivery systems for an enhanced antitumor efficiency. 相似文献
Recent work regarding the Layer by Layer (LbL) engineering of poly(lactide-co-glycolide) nanoparticles (PLGA NPs) is reviewed here.The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition,protection,cargo and release properties.LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells.LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation.The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoL-serine (DOPS) increases NP uptake and directs the NPs towards the endoplasmic reticulum.The antibody anti-TNF-α is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs.The antibody is released in cell culture following first order kinetics.The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes.The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging. 相似文献
Nanoparticles‐based drug delivery strategies have been widely researched for cancer therapy. However, most of them are expected to accumulate in tumor sites via the enhanced permeability and retention (EPR) effect, which is insufficient to deliver the loaded drug into tumors. Cell membrane–camouflaged nanoparticles have obtained much attention for their excellent stability and long blood circulation and reduced the macrophage cells uptake in drug delivery. Herein, bone marrow–derived mesenchymal stem cell membrane vesicle (SCV)–coated paclitaxel (PTX)–loaded poly (lactide‐co‐glycolide) (PLGA) nanoparticles (SCV/PLGA/PTX) were fabricated as the efficient orthotopic breast cancer–targeted drug delivery system. The SCV/PLGA/PTX showed excellent stability, more controlled PTX release, and more effective antitumor effect in vitro. After administration in vivo, SCV/PLGA/PTX exhibited the long‐term retention and enhanced accumulation at tumor sites due to the immune escape and mesenchymal stem cell–mimicking cancer‐targeting capacity. As expected, the SCV/PLGA/PTX could significantly suppress the primary tumor growth by increased apoptosis and necrosis areas within tumor tissues and attenuated the toxic side effects of PTX in 4T1 orthotopic breast cancer model. The study indicated the mesenchymal stem cell membrane coating strategy was highly efficient for targeted drug delivery, which provided a new insight for precise and effective breast cancer treatment. 相似文献
Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered‐in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water‐soluble, cytocompatible polymers are prepared via an anionic ring‐opening polymerization of a bicyclic β‐lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well‐defined polymers are mucoadhesive as documented in single‐molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers. 相似文献
The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly‐textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate‐co‐caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain‐dependent delivery of the anticancer agents cisplatin and 7‐ethyl‐10‐hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus. 相似文献
We report that human mesenchymal stem cells (hMSCs) were successfully labeled with poly(lactide‐co‐glycolide) nanoparticles (PLGA NPs) surface‐conjugated quantum dots (QDs) (PLGA‐QD NPs) via endocytosis pathway. These NPs were not toxicity even treated with PLGA‐QD NPs at high concentrations for at least four weeks. Besides, PLGA‐QD NPs‐labeled hMSCs did not change their proliferation and differentiation capability toward the cell fates of adipocytes, osteocytes, and chrondrocytes. It's known that PLGA has been widely employed to act as delivery carrier which encapsulates drugs and releases them under a controlled way. Currently, we have also demonstrated that FITC‐loaded PLGA‐QD NPs degraded in hMSCs to achieve intracellular release of FITC. The aim of this research is to investigate viability, proliferation and differentiation capability and the potential for gene delivery of MSCs labeled with PLGA‐QD NPs. In addition to PLGA‐QD NPs, QDs alone were used to serve as a control set for comparison. 相似文献