Due to their unique properties, such as controlled drug release and improved bioavailability, polymeric microparticles and nanoparticles (MPs and NPs) have gained considerable interest in the pharmaceutical industry. Nevertheless, the high costs associated with biodegradable polymers and the active pharmaceutical ingredients (APIs) used for treating serious diseases, coupled with the vast number of API-polymer combinations, make the search for effective API-polymer MPs and NPs a costly and time-consuming process. In this work, the correlation between the compatibility of selected model APIs (i.e., ibuprofen, naproxen, paracetamol, and indomethacin) with poly(lactide-co-glycolide) (PLGA) derived from respective binary phase diagrams and characteristics of prepared MPs and NPs, such as the drug loading and solid-state properties, was investigated to probe the possibility of implementing the modeling of API-polymer thermodynamic and kinetic phase behavior as part of rational design of drug delivery systems based on MPs and NPs. API-PLGA-based MPs and NPs were formulated using an emulsion-solvent evaporation technique and were characterized for morphology, mean size, zeta potential, drug loading, and encapsulation efficiency. The solid-state properties of the encapsulated APIs were assessed using differential scanning calorimetry and X-ray powder diffraction. The evaluated compatibility was poor for all considered API-PLGA pairs, which is in alignment with the experimental results showing low drug loading in terms of amorphous API content. At the same time, drug loading of the studied APIs in terms of amorphous content was found to follow the same trend as their solubility in PLGA, indicating a clear correlation between API solubility in PLGA and achievable drug loading. These findings suggest that API-polymer phase behavior modeling and compatibility screening can be employed as an effective preformulation tool to estimate optimum initial API concentration for MP and NP preparation or, from a broader perspective, to tune or select polymeric carriers offering desired drug loading.
Poly-(lactide-co-glycolide) (PLGA) is an FDA-approved biodegradable polymer which has been widely used as a scaffold for tissue engineering applications. Collagen has been used as a coating material for bone contact materials, but relatively little interest has focused on biomimetic coating of PLGA with extracellular matrix components such as collagen and the glycosaminoglycan chondroitin sulfate (CS). In this study, PLGA films were coated with collagen type I or collagen I with CS (collagen I/CS) to investigate the effect of CS on the behaviour of the osteoblastic cell line MG 63. Collagen I/CS coatings promoted a significant increase in cell number after 3 days (in comparison to PLGA) and after 7 days (in comparison to PLGA and collagencoated PLGA). No influence of collagen I or collagen I/CS coatings on the spreading area after 1 day of culture was observed. However, the cells on collagen I/CS formed numerous filopodia and displayed well developed vinculin-containing focal adhesion plaques. Moreover, these cells contained a significantly higher concentration of osteocalcin, measured per mg of protein, than the cells on the pure collagen coating. Thus, it can be concluded that collagen I/CS coatings promote MG 63 cell proliferation, improve cell adhesion and enhance osteogenic cell differentiation.
- MeSH
- Coated Materials, Biocompatible pharmacology chemistry MeSH
- Cell Engineering methods MeSH
- Cell Line MeSH
- Chondroitin Sulfates pharmacology chemistry MeSH
- Collagen Type I pharmacology chemistry MeSH
- Cells, Cultured MeSH
- Lactic Acid chemistry MeSH
- Polyglycolic Acid chemistry MeSH
- Humans MeSH
- Osteoblasts cytology physiology drug effects MeSH
- Osteogenesis physiology drug effects MeSH
- Cell Proliferation drug effects MeSH
- Materials Testing MeSH
- Tissue Scaffolds MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of -10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.
- Publication type
- Journal Article MeSH
Poly(lactic-co-glycolic acid) (PLGA) is a US Food and Drug Administration (FDA)-approved polymer used in humans in the forms of resorbable sutures, drug carriers, and bone regeneration materials. Recently, PLGA-based conjugates have been extensively investigated for cancer, which is the second leading cause of death globally. This article presents an account of the literature on PLGA-based conjugates, focusing on their chemistries, biological activity, and functions as targeted drug carriers or sustained drug controllers for common cancers (e.g., breast, prostate, and lung cancers). The preparation and drug encapsulation of PLGA nanoparticles and folate-decorated poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) conjugates are discussed, along with several representative examples. Particularly, the reactions used for preparing drug-conjugated PLGA and FA-PEG-PLGA are emphasized, with the associated chemistries involved in the formation of structures and their biocompatibility with internal organs. This review provides a deeper understanding of the constituents and interactions of PLGA-conjugated materials to ensure successful conjugation in PLGA material design and the subsequent biomedical applications.
- MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer MeSH
- Folic Acid chemistry MeSH
- Humans MeSH
- Neoplasms * MeSH
- Nanoparticles * chemistry MeSH
- Drug Carriers chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Geographicals
- United States MeSH
BACKGROUND: Nanofibrous scaffolds loaded with bioactive nanoparticles are promising materials for bone tissue engineering. METHODS: In this study, composite nanofibrous membranes containing a copolymer of L-lactide and glycolide (PLGA) and diamond nanoparticles were fabricated by an electrospinning technique. PLGA was dissolved in a mixture of methylene chloride and dimethyl formamide (2:3) at a concentration of 2.3 wt%, and nanodiamond (ND) powder was added at a concentration of 0.7 wt% (about 23 wt% in dry PLGA). RESULTS: In the composite scaffolds, the ND particles were either arranged like beads in the central part of the fibers or formed clusters protruding from the fibers. In the PLGA-ND membranes, the fibers were thicker (diameter 270 ± 9 nm) than in pure PLGA meshes (diameter 218 ± 4 nm), but the areas of pores among these fibers were smaller than in pure PLGA samples (0.46 ± 0.02 μm(2) versus 1.28 ± 0.09 μm(2) in pure PLGA samples). The PLGA-ND membranes showed higher mechanical resistance, as demonstrated by rupture tests of load and deflection of rupture probe at failure. Both types of membranes enabled the attachment, spreading, and subsequent proliferation of human osteoblast-like MG-63 cells to a similar extent, although these values were usually lower than on polystyrene dishes. Nevertheless, the cells on both types of membranes were polygonal or spindle-like in shape, and were distributed homogeneously on the samples. From days 1-7 after seeding, their number rose continuously, and at the end of the experiment, these cells were able to create a confluent layer. At the same time, the cell viability, evaluated by a LIVE/DEAD viability/cytotoxicity kit, ranged from 92% to 97% on both types of membranes. In addition, on PLGA-ND membranes, the cells formed well developed talin-containing focal adhesion plaques. As estimated by the determination of tumor necrosis factor-alpha levels in the culture medium and concentration of intercellular adhesion molecule-1, MG-63 cells, and RAW 264.7 macrophages on these membranes did not show considerable inflammatory activity. CONCLUSION: This study shows that nanofibrous PLGA membranes loaded with diamond nanoparticles have interesting potential for use in bone tissue engineering.
- MeSH
- Cell Adhesion MeSH
- Cell Line MeSH
- Diamond chemistry MeSH
- Bone Substitutes chemistry MeSH
- Lactic Acid chemistry MeSH
- Polyglycolic Acid chemistry MeSH
- Humans MeSH
- Actin Cytoskeleton metabolism MeSH
- Microscopy, Electron, Scanning MeSH
- Mice MeSH
- Nanoparticles chemistry ultrastructure MeSH
- Nanomedicine MeSH
- Nanofibers chemistry ultrastructure MeSH
- Osteoblasts cytology immunology physiology MeSH
- Cell Proliferation MeSH
- Materials Testing MeSH
- Tissue Engineering methods MeSH
- Tissue Scaffolds chemistry MeSH
- Microscopy, Electron, Transmission MeSH
- Cell Survival MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.
- MeSH
- AC133 Antigen immunology MeSH
- Immunoconjugates pharmacology MeSH
- Colorectal Neoplasms drug therapy immunology pathology MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer chemistry MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Antibodies, Monoclonal chemistry MeSH
- Nanoparticles administration & dosage chemistry MeSH
- Drug Carriers chemistry MeSH
- Oxaliplatin chemistry MeSH
- Antineoplastic Agents chemistry MeSH
- Drug Liberation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Improving the anticancer efficacy of chemotherapeutic drugs and photosensitizers requires innovative multifunctional nanoplatforms. This study introduces a chemo- and phototherapeutic drug delivery system (DDS) based on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), both PEGylated and non-PEGylated, with a mean size of 200 ± 75 nm. Colchicine (Colch) and purpurin18 (P18) were co-encapsulated into these NPs, and their in vitro drug release profiles were investigated. The anticancer potential of these systems was evaluated across various cell lines (i.e., CaCo-2, PC-3, MCF-7, and MRC-5 cells), demonstrating enhanced NP uptake by cancer cells compared to free drugs. Co-administration of Colch and P18 in 2D and 3D cell line models exhibited a synergistic effect, harnessing both chemotherapeutic and photodynamic effects, leading to higher cancer cell elimination efficacy. This newly developed multifunctional DDS presents a promising platform for combined chemo- and photodynamic therapy in cancer treatment.
- MeSH
- Spheroids, Cellular drug effects MeSH
- Photochemotherapy methods MeSH
- Photosensitizing Agents administration & dosage chemistry pharmacology MeSH
- Colchicine * administration & dosage MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer * chemistry MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasms drug therapy MeSH
- Nanoparticles administration & dosage MeSH
- Drug Carriers * chemistry MeSH
- Antineoplastic Agents administration & dosage chemistry pharmacology MeSH
- Drug Liberation * MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
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
Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80-90%. The presence of a foreign body in the human body causes disturbances in its proper functioning. It can lead to biofilm formation on the stent surface, which may favor the development of urinary tract infections or the formation of encrustation, as well as stent fragmentation, complicating its subsequent removal. In this work, the effect of the polymeric coating containing the active substance-papaverine hydrochloride on the functional properties of ureteral stents significant for clinical practice were assessed. Methods: The most commonly clinically used polyurethane ureteral Double-J stent was selected for the study. Using the dip-coating method, the surface of the stent was coated with a poly(D,L-lactide-glycolide) (PLGA) coating containing the papaverine hydrochloride (PAP). In particular, strength properties, retention strength of the stent ends, dynamic frictional force, and the fluoroscopic visibility of the stent during X-ray imaging were determined. Results: The analysis of the test results indicates the usefulness of a biodegradable polymer coating containing the active substance for the modification of the surface of polyurethane ureteral stents. The stents coated with PLGA+PAP coating compared to polyurethane stents are characterized by more favorable strength properties, the smaller value of the dynamic frictional force, without reducing the fluoroscopic visibility.
- MeSH
- Biocompatible Materials pharmacology MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer pharmacology MeSH
- Humans MeSH
- Ureteral Obstruction metabolism surgery therapy MeSH
- Papaverine metabolism pharmacology MeSH
- Polyurethanes chemistry MeSH
- Drug-Eluting Stents * MeSH
- Absorbable Implants MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
