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Hydrogels consist of three-dimensionally crosslinked polymeric chains, are hydrophilic, have the ability to absorb other molecules in their structure and are relatively easy to obtain. However, in order to improve some of their properties, usually mechanical, or to provide them with some physical, chemical or biological characteristics, hydrogels have been synthesized combined with other synthetic or natural polymers, filled with inorganic nanoparticles, metals, and even polymeric nanoparticles, giving rise to composite hydrogels. In general, different types of hydrogels have been synthesized; however, in this review, we refer to those obtained from the thermosensitive polymer poly(N-vinylcaprolactam) (PNVCL) and we focus on the definition, properties, synthesis techniques, nanomaterials used as fillers in composites and mainly applications of PNVCL-based hydrogels in the biomedical area. This type of material has great potential in biomedical applications such as drug delivery systems, tissue engineering, as antimicrobials and in diagnostic and bioimaging.

Assuntos

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Transcutaneous immunization (TCI) provides a valuable alternative approach to conventional vaccination because of the high accessibility and the exceptional immunological characteristics of the skin, but its application is limited by the low permeability of the stratum corneum. Although nanogels (NGs) have proven to enhance skin penetration of macromolecules with minimum damage, their use in TCI remains almost unexplored. In this context, this article evaluates the performance of novel film-forming NGs (FF-NGs) as TCI. This TCI platform consists of NGs with multilobular morphology that positively combines the properties of cross-linked poly(N-vinylcaprolactam), like thermoresponsiveness and the ability to load and release a cargo, with the film-forming capacity of low Tg lobes. FF-NGs and formed films are characterized at different levels. Formed films show to be able to uniformly load an antigenic protein and release it with a profile depending on the temperature and on their FF-NGs content. In vivo studies have demonstrated that FF-NGs promote the penetration of not only an antigenic protein, but also an adjuvant until the immunocompetent area of skin, generating an adjuvant-dependent specific immune response. Finally, this study provides a successful proof of concept that FF-NGs can be a powerful tool for the transcutaneous release of complex formulations.

Assuntos

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In this study, six-arm star-shaped poly(N-vinylcaprolactam) (PNVCL) polymers prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization were subjected to aminolysis reaction using hexylamine. Chemically crosslinked gels or highly end-functionalized star polymers can be obtained depending mainly on the type of solvent used during the transformation of the RAFT functional group. An increase in the viscosity of the solution was observed when the aminolysis was carried out in THF. In contrast, when the reaction was conducted in dichloromethane, chain-end thiol (PNVCL)6 star polymers could be obtained. Moreover, when purified (PNVCL-SH)6 star polymers are in contact with THF, the gelation occurs in just a few minutes, with an obvious increase in viscosity, to form physical gels that become chemically crosslinked gels after 12 h. Interestingly, when purified (PNVCL-SH)6 star polymers were stirred in distilled water, even at high aqueous solution concentration (40 mg/mL), there was no increase in the viscosity or gelation, and no evident gels were observed. The analysis of the hydrodynamic diameter (Dh) by dynamic light scattering (DLS) did not detect quantifiable change even after 4 days of stirring in water. On the other hand, the thiol groups in the (PNVCL-SH)6 star polymers were easily transformed into trithiocarbonate groups by addition of CS2 followed by benzyl bromide as demonstrated by UV-Vis spectroscopical analysis and GPC. After the modification, the (PNVCL)6 star polymers exhibit an intense yellow color typical of the absorption band of trithiocarbonate group at 308 nm. To further demonstrate the highly effective new trithiocarbonate end-functionality, the PNVCL polymers were successfully chain extended with N-isopropylacrylamide (NIPAM) to form six-arm star-shaped PNIPAM-b-PNVCL block copolymers. Moreover, the terminal thiol end-functionality in the (PNVCL-SH)6 star polymers was linked via disulfide bond formation to l-cysteine to further demonstrate its reactivity. Zeta potential analysis shows the pH-responsive behavior of these star polymers due to l-cysteine end-functionalization. By this using methodology and properly selecting the solvent, various environment-sensitive star polymers with different end-groups could be easily accessible.

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In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

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Well-defined amphiphilic, biocompatible and partially biodegradable, thermo-responsive poly(N-vinylcaprolactam)-b-poly(ε-caprolactone) (PNVCL-b-PCL) block copolymers were synthesized by combining reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerizations (ROP). Poly(N-vinylcaprolactam) containing xanthate and hydroxyl end groups (X-PNVCL-OH) was first synthesized by RAFT/macromolecular design by the interchange of xanthates (RAFT/MADIX) polymerization of NVCL mediated by a chain transfer agent containing a hydroxyl function. The xanthate-end group was then removed from PNVCL by a radical-induced process. Finally, the hydroxyl end-capped PNVCL homopolymer was used as a macroinitiator in the ROP of ε-caprolactone (ε-CL) to obtain PNVCL-b-PCL block copolymers. These (co)polymers were characterized by Size Exclusion Chromatography (SEC), Fourier-Transform Infrared spectroscopy (FTIR), Proton Nuclear Magnetic Resonance spectroscopy (1H NMR), UV-vis and Differential Scanning Calorimetry (DSC) measurements. The critical micelle concentration (CMC) of the block copolymers in aqueous solution measured by the fluorescence probe technique decreased with increasing the length of the hydrophobic block. However, dynamic light scattering (DLS) demonstrated that the size of the micelles increased with increasing the proportion of hydrophobic segments. The morphology observed by cryo-TEM demonstrated that the micelles have a pointed-oval-shape. UV-vis and DLS analyses showed that these block copolymers have a temperature-responsive behavior with a lower critical solution temperature (LCST) that could be tuned by varying the block copolymer composition.

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In this paper, chitosan was used as protective agent for dual temperature-/pH-sensitive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate)- based hydrogel nanoparticles (poly(NVCL-co-IA-co-EGDMA)) aiming avoid their undesirable colloidal destabilization at different conditions of body human tissues. Thus, poly(NVCL-co-IA-co-EGDMA) was embedded into chitosan and a new solid dispersion was prepared via spray-drying and ketoprofen was used as carrier. Two different sizes of hydrogel nanoparticles (120.6 nm and 185.9 nm) were evaluated and they exhibited a drug encapsulation efficiency of the 39.6% and 57.8%, respectively. The smaller nanoparticles showed to be faster for releasing of ketoprofen at pH 7.4 and 37 °C due to their larger surface area and higher swelling ability. Chitosan played a role of a secondary barrier for the ketoprofen diffusion, extending its release compared to hydrogel nanoparticles alone. Among two concentrations (40 wt% and 70 wt%) of hydrogel nanoparticles related to chitosan, the first one induced higher percentages of ketoprofen release: 74.2% against 64.6%. In addition, the interactions between chitosan matrix and poly(NVCL-co-IA-co-EGDMA) did not change the multi-responsive behavior of hydrogels, suggesting the chitosan was efficient for keeping integrity of nanoparticles hydrogels. Chitosan/poly(NVCL-co-IA-co-EGDMA) hybrid microparticles seems to be a promising new carrier for release of hydrophobic drugs, such as ketoprofen.

Assuntos

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A mini-library of star-shaped thermoresponsive polymers having six arms was prepared using a hexafunctional xanthate by reversible addition⁻fragmentation chain transfer (RAFT) polymerization. Star polymers with homopolymeric arms of poly(N-vinylcaprolactam) (PNVCL), copolymeric arms of poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) (PNVCL-co-PNVP) and also arms of block copolymers of PNVCL-b-PVAc, (PNVCL-co-PNVP)-b-PVAc, and combinations of them changing the order of the block was achieved exploiting the R-RAFT synthetic methodology (or R-group approach), wherein the thiocarbonyl group is transferred to the polymeric chain end. Taking advantage of the RAFT benefits, the molecular weight of the star polymers was controlled (Mn = 11,880⁻153,400 g/mol) to yield star polymers of different sizes and lower critical solution temperature (LCST) values. Removing the xanthate group of the star polymers allowed for the introduction of specific functional groups at the ends of the star arms and resulted in an increase of the LCST values. Star PNVCL-b-PVAc diblock copolymers with PVAc contents of 5⁻26 mol % were prepared; the hydrophobic segment (PVAc) is located at the end of the star arms. Interestingly, when the PVAc content was 5⁻7 mol %, the hydrodynamic diameter (Dh) value of the aggregates formed in water was almost the same sa the Dh of the corresponding PNVCL star homopolymers. It is proposed that these star block copolymers self-assemble into single flowerlike micelles, showing great stability in aqueous solution. Star block copolymers with the PVAc hydrophobic block in the core of the star, such as PVAc-b-(PNVCL-co-PNVP), form micellar aggregates in aqueous solution with Dh values in the range from ~115 to 245 nm while maintaining a thermoresponsive behavior. Micellar aggregates of selected star polymers were used to encapsulate methotrexate (MTX) showing their potential in the temperature controlled release of this antineoplasic drug. The importance of the order in which each block constituent is introduced in the arms of the star polymers for their solution/aggregation behavior is demonstrated.

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A series of thermoresponsive copolymers based on chitosan-g-poly(N-vinylcaprolactam) were synthesized by amidation reaction using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as coupling reagent. The effect of molecular architecture on the thermoresponsive properties of the graft copolymers solutions was studied by varying the chain length of the grafted poly(N-vinylcaprolactam), PVCL, (in the range from 4 to 26 kDa) and the spacing between grafted chains onto the chitosan backbone. The most interesting characteristic of these copolymers is their solubility in water at temperatures below their lower critical solution temperature (LCST). These solutions presented a LCST between 36 and 44 °C, which decreases with the spacing and length of grafted PVCL chains onto the chitosan backbone, in contrast with the limited decrease of the LCST of PVCL above a critical M¯n value around 18 kDa. This behavior offers tangible possibilities for the preparation and application of sensitive bioactive formulations and "smart" drug delivery systems.

Assuntos