Functional polymers for nanomedicine

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Nanoscale Functional Polymers for Health and Social Welfare

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We may ship the books from Asian regions for inventory purpose. Available From More Booksellers. About the Book. We're sorry; this specific copy is no longer available. New Nanosfun member — Yolanda Sabater Algarra. Solid materials with tunable reverse photochromism. In our group we work both with commercial FDA-approved polymers, as well as with novel biopolymers specifically designed for improved performance, as described next: I.

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Catechol-based Polymers Catechol derivatives are widely found in nature taking part in a variety of biological functions, ranging from the aqueous adhesion of marine organisms to the storage of transition metal ions. In this regard, the main scientific objectives of Nanosfun are: Understand the formation mechanism of polymeric NPs, to tune their structure and composition or to facilitate the conversion into novel multifunctional nanostructures.

Having control over their surface functionality or to master their properties and morphologies with enhanced properties at the nanoscale. One of the main objectives is to obtain nanostructures able to cross physiological barriers, especially BBB. The group is also exploring the boundaries of the metal-organic polymeric materials by exploring the synthesis and multifunctional properties of these new nanoplatforms, and their application in drug delivery or bioimaging field.

Design of multifunctional nanoparticles for an specific disease though direct collaboration with hospitals, medical centers and research institutes.

Introduction: Encapsulation of biologically active molecules into nanoparticles NPs , for site-specific delivery, is a fast growing area. These NPs must be biocompatible, non-toxic, and able to release their load in a controlled way. A lipophilic radiotracer has then been encapsulated into these NPs.

Functional Polymers for Nanomedicine

Methods: Monomers were synthesized from dl -aspartic acid. NPs were prepared by nanoprecipitation. Size, polydispersity, and zeta potential were measured by dynamic light scattering DLS and zetametry. Encapsulation efficacy was assessed by varying different parameters, such as encapsulation with preformed NPs or during their formation, influence of the solvent, and of the method to prepare the NPs.

Results: 99m Tc-SSS was added during nanoprecipitation, using two different methods, to ensure good encapsulation. Radiolabeled NPs present increased diameters, with identical low polydispersity indexes and negative zeta potentials in comparison to non-radiolabeled NPs. Conclusion: A radiotracer was successfully encapsulated, but some further optimization is still needed.

The next step will be to modify these radiolabeled NPs with a hepatotrope peptide, and to replace 99m Tc with Re for therapy. Nanomedicine, the use of nanoparticles NPs in medicine, is an ever-growing research field as illustrated by the huge amount of scientific publications and the important number of formulations registered for clinical trials, especially for cancer therapies 1.

From Polymers to Functional Biomaterials

Such a growing interest results from the urgent need for highly efficient anti-cancer drug delivery systems allowing an increased efficacy of the drugs together with a decrease of their non-specific distribution and toxicity 2 — 4. Indeed, despite better knowledge and understanding of cancer biology, significant improvements in cancer treatments are still needed, specifically to address a large amount of drugs at the site of action, to decrease their toxic side effects and to simplify the administration protocols. In this context, nanoparticulate systems liposomes, micelles, polymer-based NPs, etc.

However, the prepared NPs have to answer to very strict specifications: i they have to be non-toxic and biocompatible at any stage of their life, until their complete excretion from the body; ii they need to have stealth properties and reduced immunogenicity together with ability to carry large amount of drug and to deliver it at a specific site in a sustainable way.

Even if undeniable progresses have been achieved in the design of the ideal drug carriers as evidenced by the Food and Drug Administration FDA approval obtained by some nanovectors and by the number of NPs in preclinical or clinical phases 1 , 5 , 6 , several properties, such as biocompatibility, drug loading capacity and site-specificity of drug release, need to be further improved. Among the nanoplatforms designed to address these objectives, polymer-based NPs have attracted much interest mainly because of the versatile characteristics of polymers allowing adjustment of the physico-chemical and biological properties of the corresponding nanocarriers.

Consequently, several families of polymers have been developed to formulate multifunctional drug carriers with properties adjusted to the considered application 2. However, when designing a polymer family, one must keep in mind that the resulting materials are prepared to be used in vivo and that they have to respect the very strict specifications defined above. Another property which can be of importance is the bio degradability of the polymers constituting the drug delivery systems, allowing their elimination thanks to the bio degradation of the copolymers constituting the NPs, thus avoiding NPs accumulation in the body.

In this context, several bio degradable polymers have been developed and formulated under various nanoplatforms with more or less success 7 , 8. Therefore, the design of bio degradable polymers, whose physico-chemical and biological properties can be adjusted either by copolymerization, chemical modifications, or both, is of great importance 9 , These block copolymers are able to self-assemble in aqueous media, leading to well-defined NPs designed for site-specific sustainable drug release in the frame of hepatocellular carcinoma HCC.

We showed that an anti-cancer drug model, the Doxorubicin Dox , can be encapsulated into both stealth and targeted NPs with quite high encapsulation efficiency 14 , 15 and that both kind of empty NPs have no significant toxicity against normal and cancer cell lines even at high concentrations 14 — Among molecules of interest to be encapsulated, one can include radioisotopes, either for imaging diagnostic or therapy, or even both theranostics.

There is an abundant, and ever-growing literature on the subject 17 — All types of NPs have been radiolabeled 24 , from micelles 25 , polymeric NPs 26 , liposomes 27 , nanocapsules 28 , or dendrimers 29 , to inorganic ones Radiolabeling NPs enables the following of the NPs in vivo 33 , particularly as an image-guided system for targeted delivery 34 , 35 , or for the controlled delivery of a therapeutic radionuclide Due to its favorable physical and chemical properties, such as its 6-h half-life, its low energy gamma emission of keV, and relatively low isotope cost, generator-produced technetiumm 99m Tc has been the most used radionuclide in routine nuclear medicine and is still the subject of numerous investigations, in the search for new radiopharmaceuticals.

Logically, attempts to label NPs with 99m Tc have been done 26 , 30 , Rhenium Re , which is also conveniently generator-produced, like 99m Tc, has great potential for radionuclide therapy 38 , Several methods were used to encapsulate 99m Tc-SSS with more or less success. The corresponding radiolabeled NPs were characterized in terms of encapsulation efficiency, diameters, polydispersities, zeta potentials, and morphology.

Polymers in Nanomedicine

Data are reported as follows: chemical shift multiplicity, number of hydrogen. Abbreviations are as follows: s singlet , d doublet , t triplet , q quartet , dd doublet of doublet , m multiplet. All elution curves were calibrated with poly styrene standards. All chemicals were used as received. The monomer, benzyl malolactonate MLABe , was synthesized from dl -aspartic acid according to the previously reported synthesis Nanoparticles were prepared by the nanoprecipitation technique described previously Briefly, a solution of 5 mg of copolymer in acetone was rapidly added to 2 mL of water under vigorous stirring.

After 10 min of stirring at room temperature, acetone was eliminated under vacuum. The DMF or acetone solution was rapidly added into 1 mL of water under vigorous stirring. Nanoparticles were observed by TEM.

Laboratoire MAPIEM (EA 4323)

After 6 min of deposition at room temperature, non-adherent NPs were eliminated and the sample was stained by phosphotungstic acid 0. TEM imaging was performed under 80 kV accelerating voltage. Briefly, kits containing sodium gluconate and tin II chloride were first prepared as described thereafter: mg of sodium gluconate were dissolved in 9. This solution 0. In parallel, 8. Then, 0. The flasks were lyophilized and crimped. The mixture was shaken at room temperature for 15 min. Sodium dithiobenzoate 10 mg dissolved into 0. Acetone or ethanol 0. The mixture was nanoprecipitated into 2 mL of 0.

The supernatant was discarded and the pellet containing the radiolabeled NPs was resuspended into 2 mL of physiological serum. The radioactivity of the flask before and after centrifugation and resuspension was measured and the encapsulation efficiency was calculated as the ratio of the resuspended pellet activity on total activity before centrifugation. DMF or acetone 0. This organic solution was then rapidly added into 1 mL of water. The mixture was stirred at room temperature for 15 min, passed through a PD Sephadex G Medium column and eluted with 1.

After total decrease of the radioactivity, 99m Tc-radiolabeled NPs were analyzed by DLS to determine their diameter, polydispersity index, and zeta potential. The radiolabeled NPs were also observed by TEM after complete radioactive decay following the procedure described just above. MLABe was synthesized in four steps, starting from aspartic acid, following a well-described and reproducible synthetic route Figure 1 14 — 16 , After purification by precipitation, allowing the elimination of unreacted initiator and low molecular weight oligomers, block copolymers were characterized by 1 H NMR structure and molecular weight of the PMLABe block and by SEC average molecular weight and polymolecularity.

Figure 1. However, we still have to further characterize the block copolymers, especially to determine their thermal properties Tg, Tm by differential scanning calorimetry DSC , which gives an insight on the copolymer state rubber or glassy state. However, the values stayed acceptable.