Over the past few decades, with the development of science and technology, the field of biomedicine has rapidly developed, especially with respect to biomedical materials. Low toxicity and good biocompatibility have always been key targets in the development and application of biomedical materials. As a degradable and environmentally friendly polymer, polylactic acid, also known as polylactide, is favored by researchers and has been used as a commercial material in various studies. Lactic acid, as a synthetic raw material of polylactic acid, can only be obtained by sugar fermentation. Good biocompatibility and biodegradability have led it to be approved by the U.S. Food and Drug Administration (FDA) as a biomedical material. Polylactic acid has good physical properties, and its modification can optimize its properties to a certain extent. Polylactic acid blocks and blends play significant roles in drug delivery, implants, and tissue engineering to great effect. This article describes the synthesis of polylactic acid (PLA) and its raw materials, physical properties, degradation, modification, and applications in the field of biomedicine. It aims to contribute to the important knowledge and development of PLA in biomedical applications.

Purpose: Age-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases. Methods: We prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications. Results: The eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model. Conclusion: The eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.

Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of −2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

Docetaxel (DTX) is commonly used for breast cancer treatment. Tween 80 used for DTX dissolution in its clinical formulation causes severe hypersensitivity and other adverse reactions. In this study, trastuzumab (Tmab)-coated lipid-polymer hybrid nanoparticles (PLNs) were prepared, composed of poly (d, l-lactide-co-glycolide), PLGA; polyethylenimine (PEI); and lipids. The PLGA/PEI/lipid formed a hydrophobic core, while Tmab was electrostatically adsorbed on the surface of the PLNs as a ligand that targets human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. The resulting PLNs, electrostatically adsorbed Tmab-bearing PLGA/PEI/lipid nanoparticles (eTmab-PPLNs), had a mean particle size of 217.4 ± 13.36 nm, a ζ potential of 0.056 ± 0.315 mV, and good stability. In vitro, the eTmab-PPLNs showed increased cytotoxicity in HER2-postive BT474 cells but not in HER2-negative MCF7 cells. Studies of the ability of eTmab-PPLNs to target HER2 were performed. The uptake of eTmab-PPLNs was shown to be dependent on HER2 expression level. Therefore, eTmab-PPLNs provide a promising therapeutic for the treatment of breast cancer.

Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic for age-related macular degeneration (AMD). To reduce the monthly administration frequency, this study investigated microspheres comprising a poly(d, l-lactide-co-glycolide)/poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PLGA/PCADK) blend that could be loaded with bevacizumab-dextran particles using solid-in-oil-in-water (S/O/W) emulsification. Control microspheres were also prepared through water-in-oil-in-water (W/O/W) emulsification. The structural stability of bevacizumab in the polymer monomers was analyzed using dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Subsequently, microspheres were prepared and evaluated in terms of their morphology, encapsulation efficiency and release behavior. PLGA/PCADK microspheres prepared by the S/O/W method with <20% PCADK showed a smooth spherical structure with a uniform distribution of bevacizumab. The microspheres exhibited a release behavior comprising a slight initial burst and an increasing total release over 50 days both in vitro and in vivo. Additionally, the microspheres were well tolerated by ocular tissue. Finally, a chorioallantoic membrane (CAM) assay revealed that the bioactivity of bevacizumab was retained by PCADK. In conclusion, these results suggest the potential for bevacizumab-loaded PLGA/PCADK microspheres prepared by the S/O/W method as a means of intravitreal therapy for ocular diseases.