Poly(lactide-co-glycolide) nanoparticle assembly for highly efficient delivery of potent therapeutic agents from medical devices

Abstract

Controlled delivery of therapeutic agents from medical devices can improve their safety and effectiveness in vivo, by ameliorating the surrounding tissue responses and thus maintaining the functional integrity of the devices. Previously, we presented a new method for providing simultaneous controlled delivery from medical devices, by surface assembly of biodegradable polymer nanoparticles (NPs) encapsulating fluorescent dyes. Here, we continue our investigation with NPs loaded with therapeutic agents, dexamethasone (DEX) or plasmid DNA, and evaluated the bioactivity of the released molecules with macrophage cells associated with inflammation. Over a period of one week, NPs encapsulating DEX released 24.9 ± 0.8 ng from the probe surface and was successful at suppressing macrophage cell growth by 40 ± 10%. This percentage of suppression corresponded to ∼100% drug delivery efficiency, in comparison with the unencapsulated drug. DNA NP coatings, in contrast, released ∼1 ng of plasmid DNA and were effective at transfecting macrophage cells to express the luciferase gene at 300 ± 200 relative luminescence/mg total protein. This amount of luciferase activity corresponded to 100% gene delivery efficiency. Thus, NP coatings were capable of providing continuous release of bioactive agents in sufficient quantities to induce relevant biological effects in cell culture studies. These coatings also remained intact, even after 14 days of incubation with phosphate buffered saline. Although the maximum loading for NP coatings is inherently lower than the more established matrix coating, our study suggests that the NP coatings are a more versatile and efficient approach toward drug delivery or gene delivery from a medical device surface and are perhaps best suited for continuous release of highly potent therapeutic agents.

Immunization with Biodegradable Nanoparticles Efficiently Induces Cellular Immunity and Protects against Influenza Virus Infection

“…Synthetic or natural biomaterials have been used as drug-delivery carriers and as vaccine adjuvant agents (25)(26)(27). However, the advanced formulation of these materials for specific targeting and administration through various biological routes is still under investigation.…”

Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma

“…16 As mentioned by previous researchers, the zeta potential of polymersomes is an indicator of particle attachment to surfaces. 20 Polymersome assembly was ideal at a less negative zeta potential, since at a more negative zeta potential, the polymersome-to-polymersome repellent forces are higher, thus preventing a tight packing of polymersomes. 21 In our case, the zeta potential increased after loading with PpIX, thus achieving excellent negatively charged stable polymersomes.…”

Nanoparticles and their potential for application in bone

“…9,10 The following paragraph focuses on the use of nanoparticles as an effective protein or drug delivery system to support bone tissue regeneration. For this purpose, several nondegradable particles, such as silica, lipid, dendrimer, hydroxyapatite, or gold nanoparticles, [43][44][45][46][47][48][49][50] as well as degradable particles made of poly(L-lactide) 51,52 or poly(L-lactideco-glycolide) (PLGA), 11,42,[52][53][54][55][56] have been used. Frequently, nanoparticles were combined with scaffolds such as proteinaceous hydrogels or degradable polymeric matrixes to facilitate application in bone.…”

“…Frequently, nanoparticles were combined with scaffolds such as proteinaceous hydrogels or degradable polymeric matrixes to facilitate application in bone. 47,48,53,55,56 As bone contains bone-forming cells, the osteoblasts, and bone-resorbing cells, the osteoclasts, which act in concert to guarantee bone homeostasis, 57,58 different strategies can be envisioned that could promote the regeneration of bone tissue. On the one hand, osteoblasts could be supported by nanoparticle-based growth factor delivery.…”

“…The released dexamethasone did in fact lead to a local growth inhibition of such progenitors. 55 General excessive osteoclast activity, which eventually leads to bone loss or insufficient regeneration in the case of bone defects, is often treated with bisphosphonates, a class of osteoporosis-antagonizing drugs. However, orally administered bisphosphonates display poor bioavailability (only up to 3% of the ingested amount).…”