Synthesis of polylactic acid by the solid-state polycondensation of oligomers. Effect of the nanosized boron filler on the final properties of the polymer

Ermolenko Y.V., Semyonkin A.S., Ulianova Y.V., Kovshova T.S., Maksimenko O.O., Gelperina S.E.

The present analytical survey explores different aspects of hydrolytic degradation of drug dosage forms (DF) based on polylactides, homopolymers of lactic acid (PLA) and copolymers of lactic and glycolic acids (PLGA). The study includes various scientific data from multiple sources describing the effect of the PLGA nanocarrier hydrolytic degradation rate on the profile of drug release from the DFs intended for intravenous and intramuscular administration, including micro- and nanoparticles, and implants. The following aspects are explored in the review: design of experiments aimed at studying the hydrolytic degradation kinetics of PLGA carriers; commonly employed analytical methods; interpretation of the mechanism of PLGA-based DF hydrolytic degradation; factors that influence the hydrolytic degradation rate of PLGA drug carriers as part of DFs; interrelation between the processes of polymer carrier hydrolytic degradation and drug substance release from the PLGA-based DFs.

Успенский С.А., Хаптаханова П.А., Заборонок А.А., Куркин Т.С., Волкова О.Ю., Мечетина Л.В., Таранин А.Н., Каныгин В.В., Мацумура А., Таскаев С.Ю.

Stoikov I.I., Padnya P.L., Mostovaya O.A., Vavilova A.A., Gorbachuk V.V., Shurpik D.N., Evtugin G.A.

The review considers methods for modifying oligo- and polymers of lactic acid by macrocyclic moieties (cyclodextrin, tetrapyrrole, and calixarene) and the effect of modifiers on the complexing, thermal, and aggregation properties. Analytical characteristics of oligolactide-based sensors and biosensors are discussed, with particular emphasis on the mechanism of signal generation and the contribution of modified materials to the selectivity and sensitivity of analysis.

Casalini T., Rossi F., Castrovinci A., Perale G.

Polylactic acid (PLA) – based polymers are ubiquitous in the biomedical field thanks to their combination of attractive peculiarities: biocompatibility (degradation products do not elicit critical responses and are easily metabolized by the body), hydrolytic degradation in situ, tailorable properties and well–established processing technologies. This led to the development of several applications, such as bone fixation screws, bioresorbable suture threads and stent coating, just to name a few. Nanomedicine could not be unconcerned by PLA–based materials as well, where their use for the synthesis of nanocarriers for the targeted delivery of hydrophobic drugs emerged as a new promising application. The purpose of the here presented review is twofold: on one side, it aims at providing a broad overview of PLA–based materials and their properties, which allow them gaining a leading role in the biomedical field; on the other side, it offers a specific focus on their recent use in nanomedicine, highlighting opportunities and perspectives.

Kasmi N., Papageorgiou G., Achilias D., Bikiaris D.

D’Urso L., Acocella M., Guerra G., Iozzino V., De Santis F., Pantani R.

Ali M.A., Kaneko T.

Södergård A., Stolt M.

Kumari A., Yadav S.K., Yadav S.C.

Biodegradable nanoparticles have been used frequently as drug delivery vehicles due to its grand bioavailability, better encapsulation, control release and less toxic properties. Various nanoparticulate systems, general synthesis and encapsulation process, control release and improvement of therapeutic value of nanoencapsulated drugs are covered in this review. We have highlighted the impact of nanoencapsulation of various disease related drugs on biodegradable nanoparticles such as PLGA, PLA, chitosan, gelatin, polycaprolactone and poly-alkyl-cyanoacrylates.

Achmad F., Yamane K., Quan S., Kokugan T.

In order to reduce the production cost of polylactic acid (PLA), l -lactic acid was polymerized by direct polycondensation (DP) under vacuum without catalysts, solvents and initiators. Experiments were conducted at polymerization temperatures ( T p ) of 150–250 °C. The maximum PLA molecular weight obtained was 90 kDa at 200 °C after 89 h under vacuum. Above 200 °C, PLA is thermally degraded by specific scission. The DP activation energy ( E a ) was also investigated and was found to be larger than that required by catalyzed ring opening polymerization (ROP). Furthermore, the E a was higher than the deactivation energy ( E d ) for both DP and ROP. PLA yields were higher at lower T p , while the yield of lactide increased with T p . The total yield of PLA and lactide was approximately 52–75 wt.%. The uncatalyzed DP method may have applications in on-site cell plant production, where compactness is required, as well as safe and simple operating procedures.

Böhme F., Komber H., Jafari S.H.

Unsaturated aromatic polyesters were obtained by glycolysis of poly(trimethylene terephthalate) with cis-2-buten-1,4-diol followed by a solid-state polymerization. The glycolysis was performed in a batch mode as well as through a continuous process in a twin screw extruder. The degradation and subsequent rebuilding of the polymer chain during the course of reaction was followed by means of inherent and melt viscosity measurements, and 1H NMR terminal group analysis of the intermediates and the final products. Structural investigations revealed that this new approach resulted in melt processible unsaturated polyesters with cross-linkable sites having similar characteristics to that of the virgin saturated polyester. Although the processing temperature for the different reaction steps was sufficiently high (180−260 °C), no thermally induced cross-linking of the incorporated unsaturated bonds could be evidenced indicating that the obtained products remained stable during the production stage. For comparison purposes, a commercial unsaturated polyester (Vestodur©) was included in the investigations. UV irradiation of thin polyester films did not result in cross-linked products but in cis–trans isomerization of the incorporated bisoxybutenyl unit.

Gross S.M., Roberts G.W., Kiserow D.J., DeSimone J.M.

The solid-state polymerization (SSP) of small particles (20 μm) of poly(bisphenol A carbonate) resulted in high molecular weight material (Mw of 36 000 g/mol). Molecular weight distribution broaden...

Moon S.-., Lee C.-., Taniguchi I., Miyamoto M., Kimura Y.

A high polymer of poly( l -lactic acid)(PLLA) is successfully obtained by the melt/solid polycondensation of l -lactic acid (LA) catalyzed by a tin chloride dihydrate/p-toluenesulfonic acid binary system. In this process, a polycondensate with a molecular weight of 20,000 Da is first prepared by ordinary melt-polycondensation, crystallized by heat-treatment around 105°C, and heated at 140 or 150°C for 10–30 h for further polycondensation. A high-quality polymer of PLLA can be obtained in high yield in a relatively short reaction time and its molecular weight exceeds 500,000 Da which is comparable with that of the PLLA obtained by the lactide method but has never been attained by the simple melt-polycondensation.

Spaans C.J., de Groot J.H., Dekens F.G., Pennings A.J.

New biomedical polyurethanes and a polyurethane urea based on Ε-caprolactone and 1,4-butanediisocyanate have been developed. On degradation, only non-toxic products are produced. The polyurethane urea with poly(Ε-caprolactone) soft segments and butanediisocyanate/butanediamine hard segments shows a high tensile strength, a high modulus and a high resistance to tearing but as a result of the strong interactions between the solvent and the polymer processing is difficult. When butanediamine is replaced by butanediol in the chain extension step, a processible polyurethane is obtained but the polymer lacks the desired mechanical properties for biomedical applications. By chain extending with a longer urethane diol block, a processible polymer was obtained with mechanical properties comparable to the polyurethane urea. This polyurethane has been made porous and can be used as a meniscal prosthesis.

Anderson J.M., Shive M.S.

A fundamental understanding of the in vivo biodegradation phenomenon as well as an appreciation of cellular and tissue responses which determine the biocompatibility of biodegradable PLA and PLGA microspheres are important components in the design and development of biodegradable microspheres containing bioactive agents for therapeutic application. This chapter is a critical review of biodegradation, biocompatibility and tissue/material interactions, and selected examples of PLA and PLGA microsphere controlled release systems. Emphasis is placed on polymer and microsphere characteristics which modulate the degradation behaviour and the foreign body reaction to the microspheres. Selected examples presented in the chapter include microspheres incorporating bone morphogenetic protein (BMP) and leuprorelin acetate as well as applications or interactions with the eye, central nervous system, and lymphoid tissue and their relevance to vaccine development. A subsection on nanoparticles and nanospheres is also included. The chapter emphasizes biodegradation and biocompatibility; bioactive agent release characteristics of various systems have not been included except where significant biodegradation and biocompatibility information have been provided.

Khaptakhanova P., Uspenskii S., Aleksandrov A., Ryzhykau Y., Okhrimenko I.

AbstractIn this study presents a new strategy for the preparation of amphiphilic copolymers of ε‐polylysine (PL) and poly‐L‐lactic acid (PLA) using one‐step pulsed mechanochemical approach. Correlation between the synthesis parameters (ratio of homopolymers) and the structure of the resulting copolymers has been studied. The interaction products were characterized by nuclear magnetic resonance, Infrared spectroscopy, size‐exclusion chromatography, by varying the mass ratio of the initial homopolymers (PL:PLA = 10:90; 50:50; 90:10). It is shown that the largest number of product yield is formed in a ratio of homopolymers of 50:50, according to the reaction of aminolysis of polyesters. The dynamic light scattering method, transmission electron microscopy, and small‐angle x‐ray scattering were used to characterize nanoscale structures of copolymer macromolecules in aqueous solvent. As a result of pulsed mechanochemical action at all three ratios of homopolymers (PL:PLA = 10:90; 50:50; 90:10 w/w), the aminolysis reaction of the ester group occurs and branched macromolecules of copolymers are formed, which consist of chemically related sequences of homopolymers—main chain—PL, side branches—PLA. However, the maximum yield of the amphiphilic copolymer was 90 wt% with a PL:PLA ratio of 50:50. This study can serve as the development of important areas: deepen knowledge in the field of mechanochemical synthesis of amphiphilic copolymers.

Ferreira P.S., Ribeiro S.M., Pontes R., Nunes J.

AbstractBioplastics appear as an alternative to fossil fuel-derived plastics because bioplastics are carbon neutral and often biodegradable, thus potentially solving the issues of plastic pollution and climate change. In particular, polylactic acid is a substitute for traditional petrochemical-based polymers. Here, we review polylactic acid production with focus on surface modification and integration of bioactive compounds. Surface can be modified by chemical treatment, photografting, surface entrapment, plasma treatment, and coating. Bioactive compounds can be incorporated by encapsulation, impregnation, melt blending, solvent casting, electrospinning, and in situ polymerization. Biomedical and packaging applications are discussed.

Uspenskii S.A., Khaptakhanova P.A.

Boron neutron capture therapy (BNCT) is a radiotherapy method for cancer treatment based on the nuclear reaction of the stable 10B isotope with epithermal neutrons that produces high-energy particles affecting the localization site of the isotope. Currently, only two low molecular weight boron-containing compounds (boronophenylalanine and sodium mercaptododecaborate) have been approved for clinical use as targeting agents for BNCT. In spite of positive effects of these substances, certain drawbacks including the low 10B atom content per molecule and low tumor tropism make them of limited use. This review focuses on new-generation targeting agents for BNCT, such as elemental boron, boron carbide, and boron nitride nanoparticles (NPs). Their main advantage is the high content of 10B atoms, e.g., a 3-nm elemental boron NP contains 12000 atoms (cf. 20000 atoms for a 50-nm NP). This allows one to reach the concentration range necessary for successful implementation of BNCT. Information is analyzed and summarized on methods for the synthesis and biological applications of the title targeting agents for BNCT and combined chemotherapy, where NPs can also simultaneously act as drug carriers.