Over the recent decades, hyperbranched polymers have received much attention in both academic and industrial sphere. Due to their highly branched structure and multifunctionality, hyperbranched polymers exhibit unique chemical and physical properties. Many hyperbranched polymers have been prepared by one-step polymerization. The polymerizations can be divided into three categories: step-growth polycondensation of ABx monomers, selfcondensative vinyl polymerization of AB* monomers and branching ring-opening polymerization of hypothetical ABx monomers. This review highlights some examples of synthesis of the most important hyperbranched polymers. Special attention is paid to step-growth polycondensation of ABx-type monomers and to polycondensation of A2 and B3 monomers. Some properties of hyperbranched polymers and their potential applications are also described.
Polyester-based nanostructures are widely studied as drug-delivery systems due to their biocompatibility and biodegradability. They are already used in the clinic. In this work, we describe a new and simple biodegradable and biocompatible system as the Food and Drug Administration approved polyesters (poly-ε-caprolactone, polylactic acid, and poly(lactic- co-glycolic acid)) for the delivery of the anticancer drug paclitaxel (PTX) as a model drug. A hydrophobic polyester, poly(propylene succinate) (PPS), was prepared from a nontoxic alcohol (propylene glycol) and monomer from the Krebs's cycle (succinic acid) in two steps via esterification and melt polycondensation. Furthermore, their amphiphilic block copolyester, poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) (mPEO- b-PPS), was prepared by three steps via esterification followed by melt polycondensation and the addition of mPEO to the PPS macromolecules. Analysis of the in vitro cellular behavior of the prepared nanoparticle carriers (NPs) (enzymatic degradation, uptake, localization, and fluorescence resonance energy-transfer pair degradation studies) was performed by fluorescence studies. PTX was loaded to the NPs of variable sizes (30, 70, and 150 nm), and their in vitro release was evaluated in different cell models and compared with commercial PTX formulations. The mPEO- b-PPS copolymer analysis displays glass transition temperature < body temperature < melting temperature, lower toxicity (including the toxicity of their degradation products), drug solubilization efficacy, stability against spontaneous hydrolysis during transport in bloodstream, and simultaneous enzymatic degradability after uptake into the cells. The detailed cytotoxicity in vitro and in vivo tumor efficacy studies have shown the superior efficacy of the NPs compared with PTX and PTX commercial formulations.
- MeSH
- Micelles MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Nanoparticles adverse effects chemistry metabolism MeSH
- Paclitaxel administration & dosage pharmacokinetics MeSH
- Polyesters chemical synthesis chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polypropylenes chemistry MeSH
- Antineoplastic Agents administration & dosage pharmacokinetics MeSH
- Succinates chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Biocompatible polymers derived from ? -hydroxyacids, in particular homopolymers and copolymers of lactic and glycolic acids, are widely used in surgery, tissue engineering and drug formulation. Their polycondensation with polyhydric alcohols yields degradable low-molecularweight branched oligoesters. Polymer plasticizers improve processibility, decrease brittleness and impart mechanical endurance to the oligoesters. Out of many plasticizers used in polymers, only a few of them have been approved for pharmaceutical applications. The type and amount of plasticizers influence the degradation time of polymers and thus the drug release. Biodegradable polyesters are currently used in parenteral drug delivery as solid implants, microparticles and in-situ implants. Homopolymers and copolymers of lactic and glycolic acids are suitable drug carriers for the purpose in treatment of cancer, drug addiction, contraception and vaccination as well as for the controlled release of growth factors in tissue engineering.
Despite several shortcomings such as extreme hydrophobicity, low drug capacity, characteristic triphasic drug release pattern with a high burst effect, poly(lactic-co-glycolic acid derivatives are widely used in drug delivery. Most frequent attempts to improve their properties are blending with other polymers or synthesis of block copolymers. We introduce a new class of branched poly(lactic-co-glycolic acid) derivatives as promising biodegradable carriers for prolonged or targeted drug release systems, employed as thin adhesive films, solid dispersions, in situ forming implants or nanoparticles. A series of poly(lactic-co-glycolic acid) derivatives with lower molar mass and star or comb architecture were synthesized by a simple, catalyst free, direct melt polycondensation method not requiring purification of the obtained sterile product by precipitation. Branching monomers used were mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and polyacrylic acid. The products were characterized by molar mass averages, average branching ratio, rheological and thermal properties.
- MeSH
- Chemistry, Pharmaceutical methods MeSH
- Technology, Pharmaceutical methods MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer chemistry MeSH
- Drug Delivery Systems * MeSH
- Drug Carriers chemistry MeSH
- Rheology MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
In an attempt to prepare a library of short oligoadenylate analogues featuring both the enzyme-stable internucleotide linkage and the 5'-O-methylphosphonate moiety and thus obtain a pool of potential RNase L agonists/antagonists, we studied the spontaneous polycondensation of the adenosin-5'-O-ylmethylphosphonic acid (p(c)A), an isopolar AMP analogue, and its imidazolide derivatives employing N,N'-dicyclohexylcarbodiimide under nonaqueous conditions and uranyl ions under aqueous conditions, respectively. The RP LC-MS analyses of the reaction mixtures per se, and those obtained after the periodate treatment, along with analyses and separations by capillary zone electrophoresis, allowed us to characterize major linear and cyclic oligoadenylates obtained. The structure of selected compounds was supported, after their isolation, by NMR spectroscopy. Ab initio calculation of the model structures simulating the AMP-imidazolide and p(c)A-imidazolide offered the explanation why the latter compound exerted, in contrast to AMP-imidazolide, a very low stability in aqueous solutions.
- MeSH
- Adenine Nucleotides chemistry metabolism MeSH
- Adenosine Monophosphate analogs & derivatives MeSH
- Models, Molecular MeSH
- Molecular Structure MeSH
- Nuclear Magnetic Resonance, Biomolecular MeSH
- Oligoribonucleotides chemistry metabolism MeSH
- Oxidation-Reduction MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The high interest in polymers from natural resources prompted us to investigate the use of enzymatically synthesized polyglobalide (PGL) in the preparation of polymer networks with potential applications as biomaterials for drug delivery devices. Polymer networks were obtained under mild conditions by photoinitiated thiol-ene coupling between PGL and a poly(ethylene glycol- co-thiomalate) (PEG-SH) copolymer obtained by polycondensation. The obtained polymer networks were thoroughly characterized by Raman spectroscopy, scanning electron microscopy, titration of thiol groups and elemental analysis. Our study took into consideration the synthesis parameters for the polymer networks, such as the total polymer concentration and the SH/C=C functionality molar ratio. Swelling in both THF and water was assessed, and the potential of the materials for drug delivery was determined. The scanning electron microscopy images showed that the prepared polymer networks may have different morphologies ranging from homogeneous polymer materials to macroporous structures. Additionally, the prepared materials were found to be suitable from a cytotoxicity point of view, enabling their application as biomaterials for drug delivery devices.
- MeSH
- 3T3 Cells MeSH
- Esters chemistry MeSH
- Hydrogels adverse effects chemical synthesis chemistry MeSH
- Lactones chemistry MeSH
- Mice MeSH
- Polyethylene Glycols chemistry MeSH
- Sulfur Compounds chemistry MeSH
- Ultraviolet Rays MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aim of this work was to investigate the potential of an amphiphilic system comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide acid as a carrier for the controlled release and co-release of two DNA alkylating drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized polylactide acid were obtained through direct melt polycondensation reaction, using methanesulfonic acid as a non-toxic initiator, and subsequently these were grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and conductometric titration confirmed that a reaction between CS and PLA, PLACA2% and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid nanoparticles were prepared via the polyelectrolyte complex technique, applying dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide. The diameter of particles, ζ-potential and their relationship to temperature and pH were analysed in all formulations. Encapsulation, co-encapsulation efficiency and release studies were conducted in different physiological simulated environments and human serum. Results showed the continuous release of drugs without an initial burst in different physiological media.
- MeSH
- Chitosan administration & dosage chemistry MeSH
- Dacarbazine administration & dosage analogs & derivatives chemistry therapeutic use MeSH
- Doxorubicin administration & dosage chemistry therapeutic use MeSH
- Lactic Acid administration & dosage chemical synthesis chemistry MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Molecular Structure MeSH
- Nanoparticles administration & dosage chemistry MeSH
- Polymers administration & dosage chemical synthesis chemistry MeSH
- Surface-Active Agents administration & dosage chemistry MeSH
- Surface Properties MeSH
- Temperature MeSH
- Particle Size MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Chitosan and chitosan-grafted polylactic acid as a matrix for BSA encapsulation in a nanoparticle structure were prepared through a polyelectrolyte complexation method with dextran sulfate. Polylactic acid was synthetized via a polycondensation reaction using the non-metal-based initiator methanesulfonic acid and grafted to the chitosan backbone by a coupling reaction, with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as the condensing agent. The effect of concentration of the polymer matrix utilized herein on particle diameter, ζ-potential, encapsulation efficiency, and the release kinetic of the model protein bovine serum albumin at differing pH levels was investigated. The influence of pH and ionic strength on the behavior of the nanoparticles prepared was also researched. Results showed that grafting polylactic acid to chitosan chains reduced the initial burst effect in the kinetics of BSA release from the structure of the nanoparticles. Furthermore, a rise in encapsulation efficiency of the bovine serum albumin and diminishment in nanoparticle diameter were observed due to chitosan modification. The results suggest that both polymers actually show appreciable encapsulation efficiency; and release rate of BSA. CS-g-PLA is more suitable than unmodified CS as a carrier for controlled protein delivery.
- MeSH
- Chitosan chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Lactic Acid chemistry MeSH
- Delayed-Action Preparations MeSH
- Molecular Weight MeSH
- Nanoparticles chemistry MeSH
- Polymers chemistry MeSH
- Solubility MeSH
- Serum Albumin, Bovine chemistry MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
