scholarly journals Selected Physicochemical and Pharmaceutical Properties of Poly-ε-caprolactone and Poly(d,l-lactide-co-ε-caprolactone) Conjugates of Lamivudine Synthesized via Ring-Opening Polymerization

Polymers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2124
Author(s):  
Tomasz Urbaniak ◽  
Witold Musiał
Keyword(s):  
Molecular Weight ◽  
Drug Release ◽  
Physicochemical Properties ◽  
Ring Opening ◽  
Ring Opening Polymerization ◽  
Submicron Particles ◽  
Degree Of Crystallinity ◽  
Side Reactions ◽  
Burst Release ◽  
Reaction Products

The modification of drug fate after administration may be achieved by the covalent coupling of active pharmaceutical ingredients with macromolecules. To prolong or delay the release, slowly degrading polymers such as polyesters may be applied for conjugation. The detachment of a covalently conjugated drug from the polymeric matrix relies mostly on the material degradation profile and barely on the weak interaction between the drug and macromolecules. In the present study, lamivudine was conjugated via ring-opening polymerization with poly-ε-caprolactone and poly(d,l-lactide-co-ε-caprolactone). The influence of the reaction parameters on the course of the polymerization and physicochemical properties of obtained conjugates were investigated. Subsequently, selected reaction products were formulated into submicron particles, and drug release profiles in physiological-like conditions were investigated. The course of the reaction was monitored via gel permeation chromatography. The structure and physicochemical properties of products were evaluated via spectroscopic, calorimetric, and diffractometric methods. The profile of the drug release from particles prepared by the slow evaporation of conjugate solution from o/w emulsion was monitored with high-performance liquid chromatography. Both an elevated reaction temperature and higher catalyst concentration increased the polymerization rate and simultaneously promoted the side reactions, resulting in a broad molecular weight distribution of products in the range from 1.30 to 2.15. The physicochemical properties of conjugates obtained in different conditions varied and had a direct influence on the drug release. The release curve of lamivudine from particles based on low molecular weight conjugates achieved a plateau between 18.9 and 22.2 μg per mg of conjugate within a month. Drug detachment from particles composed of high molecular weight conjugates exhibited a distinct delay period preceded by a drug burst release at a maximal level of 13.3 μg per mg of conjugate. Conjugate chemical composition and the degree of crystallinity were also found to influence the release.

scholarly journals End-Group Evaluation of HEMA Initiated Poly(ε-caprolactone) Macromonomers via Enzymatic Ring-Opening Polymerization

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
N. Ugur Kaya ◽  
Y. Avcibasi Guvenilir
Keyword(s):  
Molecular Weight ◽  
Ring Opening ◽  
Average Molecular Weight ◽  
Gel Permeation Chromatography ◽  
Ring Opening Polymerization ◽  
Enzyme Concentration ◽  
Polymer Chains ◽  
Side Reactions ◽  
Initiator Concentration ◽  
Lower Temperature

Poly(ε-caprolactone) (PCL) macromonomers comprising acrylate end-functionality were synthesized via enzymatic ring-opening polymerization (eROP) by utilizing commercially availableCandida antarcticaLipase B (CALB), Novozyme-435. 2-Hydroxyethyl methacrylate (HEMA) was purposed to be the nucleophilic initiator in eROP. The side reactions generated due to the cleavage of ester bonds in HEMA and the growing polymer chains were investigated through altering polymerization period, initiator concentration, temperature, and enzyme concentration.1H NMR evaluations showed that minimum quantities of side reactions were in lower temperatures, initiator concentration, enzyme concentration, and lower monomer conversions. Gel permeation chromatography (GPC) results revealed that lower polydispersity along with number-average molecular weight of end-functionalized PCL macromonomers was obtained depending on higher initiator/monomer ratios, lower temperature (60°C), enzyme concentration (100 mg), and/or polymerization time (2 h). Furthermore, 0.1 HEMA/ε-caprolactone (CL) ratio had higher molecular weight than 0.5 HEMA/CL ratio, while keeping a close value of methacrylate transfer, total methacrylate end-groups, and lower polyester transfer.

Catalytic Ring-Opening Polymerization of Renewable Macrolactones to High Molecular Weight Polyethylene-like Polymers

2011 ◽  
Vol 44 (11) ◽  
pp. 4301-4305 ◽  
Author(s):  
Inge van der Meulen ◽  
Erik Gubbels ◽  
Saskia Huijser ◽  
Rafaël Sablong ◽  
Cor E. Koning ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Ring Opening ◽  
Ring Opening Polymerization

The synthesis and polymerization behaviour of silicon-bridged [1]- and [2]ferrocenophanes with sterically demanding trimethylsilyl substituents attached to the cyclopentadienyl rings

1995 ◽  
Vol 73 (11) ◽  
pp. 2069-2078 ◽  
Author(s):  
Timothy J. Peckham ◽  
Daniel A. Foucher ◽  
Alan J. Lough ◽  
Ian Manners
Keyword(s):  
Molecular Weight ◽  
Ring Opening ◽  
Ring Opening Polymerization ◽  
Monoclinic Space Group ◽  
Organometallic Polymers ◽  
X Ray Diffraction ◽  
X Ray ◽  
Cyclopentadienyl Ligands ◽  
Sterically Demanding ◽  
High Molecular Weight Poly

The silicon-bridged [1]ferrocenophane Fe(η-C5H3SiMe3)2(SiMe2) (5) was synthesized via the reaction of Li2[Fe(η-C5H3SiMe3)2]•tmeda (tmeda = tetramethylethylenediamine) with Me2SiCl2 in hexanes. The disilane-bridged [2]ferrocenophane Fe(η-C5H3SiMe3)2(Si2Me4) (7) was prepared using a similar route from the disilane ClMe2SiSiMe2Cl. Despite the presence of sterically demanding SiMe3 substituents on the cyclopentadienyl rings, compound 5 was found to undergo thermal ring-opening polymerization at 170 °C to produce very soluble, high molecular weight poly(ferrocenylsilane) 6 with Mw = 1.4 × 105, Mn = 8.4 × 104. However, the [2]ferrocenophane 7 was found to be resistant to thermal ring-opening polymerization even at 350 °C and decomposed above 380 °C. A single-crystal X-ray diffraction study of 7 revealed that the steric interactions between the bulky SiMe3 groups are relieved by a significant twisting of the disilane bridge with respect to the plane defined by the centroids of the cyclopentadienyl ligands and the metal atom. The angle between the planes of the cyclopentadienyl rings in 7 was found to be 5.4(6)°, slightly greater than that in the non-silylated analogue Fe(η-C5H4)2(Si2Me4) (4a) (4.19(2)°), and dramatically less than the corresponding tilt angle of the strained, polymerizable, silicon-bridged [1]ferrocenophane Fe(η-C5H4)2(SiMe2) (1) (20.8(5)°). The length of the Si—Si bond in 7 (2.342(3) Å) was found to be close to the sum of the covalent radii (2.34 Å). Crystals of 7 are monoclinic, space group C2/c, with a = 23.689(3) Å, b = 11.174(1) Å, c = 31.027(3) Å, β = 109.16(1)°, V = 7758(2) Å3, and Z = 12. Keywords: ring-opening polymerization, ferrocenophane, organometallic polymers.

Biodegradable Polymers Derived from Amino Acids for Biological Applications

2010 ◽  
Vol 76 ◽  
pp. 30-35 ◽  
Author(s):  
Naomi Cohen-Arazi ◽  
Ilanit Hagag ◽  
Michal Kolitz ◽  
Abraham J. Domb ◽  
Jeoshua Katzhendler
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Ring Opening ◽  
Building Blocks ◽  
Ring Opening Polymerization ◽  
Microwave Assisted Synthesis ◽  
Hydroxy Acids ◽  
Natural Amino Acids ◽  
Direct Condensation ◽  
Positively Charged

Optically active α-hydroxy acids derived from amino acids have been synthesized and polymerized into new biodegradable polyesters. The variety of functional side chains enables the design of positively charged, negatively charged, hydrophobic and hydrophilic chiral building blocks or any combination of these constituents. Hydroxy acids of 15 natural amino acids were prepared with retention of configuration using a straightforward and reliable method of diazotization of α-amino acids. Polyesters were synthesized from these hydroxy acids by a number of methods: direct condensation in bulk, microwave assisted synthesis and ring opening polymerization. The molecular weight of the prepared polymers ranges between 2000 to 5000Da for the direct condensation and the microwave methods, whereas the ring opening polymerization results in high molecular weight polymers (20000 to 30000Da). The polymers were analyzed for their optical activity (Circular Dichroism Spectroscopy), thermal properties (DSC), solubility, molecular weight and polydispersity (GPC), and aqueous degradation. These polymers were tested for their compatibility to neuronal cells growth and differentiation.

Article

1998 ◽  
Vol 76 (4) ◽  
pp. 371-381 ◽  
Author(s):  
Ian Manners
Keyword(s):  
Molecular Weight ◽  
Transition Metal ◽  
High Molecular Weight ◽  
Ring Opening ◽  
Ring Opening Polymerization ◽  
Metal Catalysts ◽  
Transition Metal Catalysts ◽  
Organometallic Polymer ◽  
Wide Range ◽  
Initial Discovery

Ring-opening polymerization (ROP) of strained ring-tilted metallocenophanes can be achieved thermally, via anionic or cationic initiation, or by the use of transition-metal catalysts and provides access to a wide range of high molecular weight (Mw = 105-106, Mn > 105) poly(metallocenes). These materials possess a variety of interesting properties and many are very easy to prepare. This article provides an overview of our work, giving background to and an account of the initial discovery, and discusses work on the synthesis and properties of new poly(metallocenes) and related materials with particular emphasis on recent research directions.Key words: metallocene, ring-opening polymerization, ferrocenophane, organometallic polymer.

Diol glycidyl ether-bridged low molecular weight PEI as potential gene delivery vehicles

2015 ◽  
Vol 3 (13) ◽  
pp. 2660-2670 ◽  
Author(s):  
Qian Guo ◽  
Yan-Hong Liu ◽  
Miao-Miao Xun ◽  
Ji Zhang ◽  
Zheng Huang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Gene Delivery ◽  
Ring Opening ◽  
Transfection Efficiency ◽  
Glycidyl Ether ◽  
Ring Opening Polymerization ◽  
Low Molecular Weight ◽  
Delivery Vehicles ◽  
Gene Delivery Vehicles

PEI 600-based polymers were synthesized via ring-opening polymerization and exhibited much better transfection efficiency and biocompatibility than PEI 25 kDa.

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