Biodegradable "polylactic acid" modification and its application (2)

3.1 Application in Biomedicine

At present, there are dozens of medical polymer materials available such as polytetrafluoroethylene, silicone oil, and silicone rubber. However, from a biomedical point of view, these materials are not ideal and have some side effects during use. Polylactic acid is A new medical polymer material came into being. Aliphatic polyesters are used for tissue fixation (eg, bone screws, fixation plates and plugs), drug delivery systems (eg, diffusion control), wound dressings (eg, artificial skin), and wound closure (eg, application of sutures, surgical supplies). Bone screws, bone fixation plates, and biological organ nails made from polylactic acid and copolymers of DL2 lactic acid and glycolic acid have been used and may replace metal grafts in the near future. These bioresorbable products have several advantages over metal implants: (1) no stress shielding; (2) no need to be removed after surgery; (3) no metal corrosion products.

3.1.1 Drug controlled release system Biodegradable polymer microspheres are another novel drug carrier following liposomes, emulsions, and natural polymer microcapsules. By adjusting the copolymerization of lactic acid and other monomers, PLA copolymers with different properties such as PLGA, PELA, and the like are formed. Polylactic acid (PLA) and its copolymers are used as biodegradable polymers because of their excellent biodegradability and biocompatibility. They are used as some poor stability, susceptibility to degradation, easily digested by digestive enzymes, difficult to absorb and toxic The erodible materials of drug controlled-release preparations with large side-effects effectively broaden the route of administration, reduce the number of administrations and dosages, increase the bioavailability of drugs, and minimize the toxic side effects of drugs on the whole body, especially the liver and kidneys. Therefore, it is widely used in drug release technology. Drug-loaded microspheres made from polylactic acid and its copolymers have good effects in terms of sustained release, targeted release, and increased drug efficacy. Wuhan Liyuanheng Pharmaceutical Technology Co., Ltd. Yi Yimu developed a ursolic acid polylactide nanoparticle freeze-dried powder injection, which has a liver-targeting effect, can inhibit and kill hepatoma cells, and reduce the expression of p53, bcl22, and ToppoII. .

There are several techniques for embedding a drug in a polymer matrix to form microspheres or microparticles: agglutination, emulsion polymerization and interfacial polymerization, interfacial deposition, emulsion-solvent evaporation, and the like. Among them, the emulsion-solvent evaporation method is the most commonly used one. Most oily drug microspheres use OPW emulsifying solvent volatilization P extraction method. Hydrophilic peptides, proteins, and vaccine microspheres are prepared by phase separation and W1POPW2 double emulsion solvent evaporation.

The interfacial deposition method can also be referred to as self-emulsifying P-solvent diffusion method, which is a method for preparing uniform nano-sized microspheres. Fishbein et al. used this method to prepare PLA nanoparticles loaded with tyrosine phosphorylation inhibitors; biologically active protein drugs can also be embedded in polymer nanoparticles by this method. Kamashima et al. used PLGA as insulin. The carrier material was made into nanoparticles using a self-emulsifying P-solvent diffusion method and administered through the lungs. Animal experiments have shown that polymer nanoparticle administration has a significant hypoglycemic effect compared to direct administration with insulin solution, and has a long duration. This method has the advantages of good repeatability, large drug wrap, and uniform particles.

Kumar et al. used PLGA microspheres of a specific size and shape stabilized with a PVA2 chitosan blend to form PLGA microspheres for DNA transport by emulsion 2 solvent evaporation techniques, and characterized the microparticles by atomic force microscopy AFM, PCS, and FTIR. Zeta potential and gel electrophoresis were used to study the surface properties of the microparticles and their ability to concentrate DNA. The results show that spherical particles of uniform size can be formed and DNA can be efficiently loaded. This is the most commonly used method for preparing water-soluble peptides and protein drug microspheres. It has the advantages of high drug loading, good protein stability, porous surfaces on microspheres, and easy release of drugs.

Peptide protein drugs have good water solubility. If the OPW method is used, it will cause the drug to transfer from the oil phase to the aqueous phase. The resulting microspheres have a low drug embedding rate; however, the use of the OPO method will often lead to denaturation and deactivation of the drug. The W1POPW2 double emulsion solvent evaporation method can solve this problem and is therefore widely used in the preparation of such drug microspheres. Li Xiaohong and others used the W1POPW2 method to prepare serum white eggs PELA microspheres, the spherical microspheres regular, particle size concentrated in the 015 ~ 510μm, burst release phenomenon is not obvious, the release rate is relatively constant. Meng et al. used this method to use hemoglobin as a mimic protein and PLA2PEG block copolymer as a carrier material for drug-loaded microspheres to prepare PELA microspheres.

Perez et al. used the optimized WPOPW emulsion solvent evaporation technique and a new WPO emulsion P solvent diffusion technique to prepare DNA containing free DNA or encapsulated in PVA or polyvinylpyrrolidone (PVP). Polylactide-2-polyvinyl alcohol (PLA2PEG) microparticles, the results show that plasmid DNA can be effectively encapsulated, in addition, depending on the processing conditions, these microparticles release rate can be slower or slower. Shanghai University Yin Jingbo et al used WPOPW double-emulsion solvent evaporation method to prepare 52FuPPLA and 52FuPPLA2PEG microspheres containing nano-silica, using nano-silica nano-adsorption and its surface groups on 52Fu, so that the drug loading Up to 39.9%, effectively reduce the toxic side effects of fluorouracil and improve drug utilization.

In order to minimize the destruction of proteins by organic solvents in the preparation process, in view of the stability of the protein in the solid state than in the aqueous solution, many microsphere preparation techniques using non-aqueous protein encapsulation have emerged, such as spray drying and supercritical fluid technology. , cold spray drying technology.

3.1.2 Orthopaedic Fixation and Tissue Repair Materials Tissue engineering is the cultivation of high-concentration tissue cells cultured in vitro in biological scaffolds to form a bioactive implant. When implanted in the lesion, biomaterials are degraded and absorbed. Tissues or organs are formed to reach the tissue or organ that repairs or rebuilds the defect. Its core is to construct three-dimensional composite materials for planting cells and biological materials. The fracture internal fixation material requires the implanted polymer to slowly degrade during the wound healing process, such as bone splints and bone screws. The tissue repair material requires the polymer to slowly degrade in a relatively short period of time, and the tissue cells are cultured on the material at the initial stage or for a certain period of time. It grows into tissues and organs such as cartilage, liver, blood vessels, nerves and skin. Polylactic acid is used as an orthopaedic anchor material and its initial strength and load carrying capacity can already be comparable to metal screws.

As we all know, the traditional fracture fixation material is generally made of stainless steel, titanium and its alloys, but it mainly has the following three defects. As early as 1971, Kulkarm and others first began to study the PLA as a fracture fixation material. The initial strength of the rod-shaped material they prepared was as high as 42 to 51 MPa, and a 2 mm-thick PLA sheet was used for the monkey iliac bone test. Getter et al. used PLA as a bone plate and bone nail for dog fracture fixation. The test results showed that the mechanical strength of the fracture internal fixation material manufactured by the conventional injection molding method and compression molding method could not meet the clinical requirements. In the 1990s, Bostman and Claes et al. used PLLA as the internal fixation material for fracture fixation to obtain satisfactory results. However, due to slow degradation, there was a delayed foreign body reaction leading to aseptic inflammatory complications. Better PDLLA has once again aroused people's interest. Rohman et al. made poly-DL2 lactide P polymethyl methacrylate as the substrate semi-interpenetrating network, which can be used as a precursor of the porous network with adjustable pore size.

At present, PLA material as an internal fixation material of orthopedic insufficiency has the following aspects: (1) It does not have osteoconductivity, and the rate of repairing bone defects is very slow. For larger bone defects, it is difficult to achieve complete bone repair; ( 2) The mechanical strength of the material is not enough to be used as a fracture internal fixation material for the bearing site; (3) The early biodegradation rate is so fast that it can not be guaranteed to meet the requirements of the mechanical properties before the new bone tissue grows, and the intermediate degradation is required. The speed is too slow, so that after the new bone tissue grows, there are still residues left in the body to cause complications; (4) Japanese scholars reported in 1995 that PLA has a carcinogenic effect, and its experimental rate was as high as 44%, but there are also Scholars questioned their experimental design, so this issue needs to be observed for a long time.

Tissue Engineering This method has been tried in skin cells, embryonic stem cells, cartilage, vascular repair, nerve repair, retinal pigment epithelial (RPE) cells, and bone. The bottom layer porous, top-dense bilayer membrane is made of PLLA as a skin substitute substrate, the bottom layer is for adhesion to the skin and the wound, and the top layer is for cell culture, and can be used for the treatment of third-degree burns and large-scale skin defects at the transplantation site and The whole animal is free from allergic reactions. Because of their versatility and proliferative capacity, embryonic stem cells are expected to become a source of cells for tissue engineering and regeneration. Kimberley et al. found that PLGA microspheres serve as a transport system for biological activity and a scaffold for multifunctional cells. It is noteworthy that its research also proves that PLGA microspheres are expected to be used for the transplantation of multi-functional cells for tissue engineering and regeneration. Wu Yuhua and others from Wuhan University of Technology have developed composite polylactic acid sustained-release artificial nerve catheter material, which is a composite of bioabsorbable polylactic acid and nano-hydroxyapatite powder and nerve growth factor-inducing nerve growth factor (NGF). Human nerve defect, its repair effect, and autologous nerve graft similar.

3.1.3 Surgical sutures For a long time, surgical absorbable surgical sutures have been mainly gut gills and recently developed PGA surgical sutures. Although these two sutures are widely used in surgery, they are used in sutures and knots. All of them are more difficult. The gut is prone to produce antibody reactions. The strength of the gut is reduced during the process of absorption by the body. The PGA line has poor resistance to bacteria and is easily decomposed in the air. Polylactic acid and its copolymer sutures are soft and easy to dye, and sewing and knotting are more convenient. In addition, this type of polymer also has the characteristics of good biocompatibility, and can change the composition of the copolymer to control the absorption cycle. The surgical suture synthesized from glycolide and lactide has been successfully applied in clinical treatment.

Due to the mechanical strength requirements of sutures, surgical sutures are usually made by melting or solution spinning with high molecular weight PLA. A large number of studies have investigated the effect of polymerization conditions on the molecular weight of PLA and the effects of dry spinning, wet spinning, and stretching conditions on the crystallinity and tensile strength of sutures. Suesat et al. investigated the effect of spinning parameters on fiber tensile properties and structure. To increase the flexibility of the suture, a limited amount of plasticizers such as collagen, low molecular weight PLA, various inorganic salts, etc. are added to the polymer to make the suture more flexible. When PLA fibers are used as surgical sutures, local inflammation and foreign body rejection will disappear over time.

3.1.4 Ophthalmic implant material Retinal detachment is a serious blinding eye disease, usually through surgery, implantation of filler on the surface of the eye sclera, and combined with laser, frozen and other medical means to heal the hole. Currently, such fillers are usually made of silicone rubber or silicone sponge. Since these two materials are non-biodegradable materials, they often cause different levels of foreign body reactions, and polylactic acid can solve this problem. Wuhan University Zhuo Renxuan made polylactic acid into a film with a thickness of about 1 mm using a solvent evaporation method. The patch was implanted on the scleral surface of a rabbit's eye, and the height of the sclera lifted by the diaphragm was measured by a B-ultrasonic test. Observe its in vivo degradation performance. The results showed that polylactic acid film not only has certain degradability in the tissue, but also meets the requirement of retinal detachment repair surgery on the duration of the scleral bleb. It is an ideal filling material.

3.2 Application of PLA in Textile Field

The research and application development of PLA in the textile field started in the last 10 years or so. The polylactic acid can be directly made into a non-woven fabric by a spunbonding method or a melt-blown method, or can be firstly spun into a short fiber, and then a non-woven fabric can be obtained by a dry method or a wet method. Polylactic acid nonwovens are used in agriculture and horticulture. They can be used as seeds for cultivation, breeding, frost prevention and weeding. They can be used as surgical gowns, surgical coverings, masks, etc. Diapers, feminine napkins, fabrics, and other sanitary products; for daily necessities, cloth, wipes, kitchens