Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study

Abstract

Nanoparticles are increasingly utilized as drug delivery agents. Previously, we have developed a drug delivery system based on amphiphilic derivatives of poly-N-vinylpyrrolidone (PVP-OD4000) with excellent biocompatibility. In the current study, we assessed the pharmacokinetics, anti-inflammatory profile, and ulcerogenic potential of indomethacin (IMC)-loaded PVP-OD4000 nanoparticles compared to the free drug. Wistar male rats were utilized for a pharmacokinetics study and an anti-inflammatory study. Loaded IMC exhibited a slower elimination rate (p < 0.05) and a higher blood plasma concentration at 8 and 24 h after intraperitoneal injection compared with free IMC. In addition, decreased uptake of loaded IMC in the liver and kidney compared to free IMC (p < 0.05) was detected. Furthermore, PVP-OD4000 nanoparticles loaded with IMC showed an enhanced anti-inflammatory effect compared to free IMC (p < 0.05) in carrageenan-induced and complete Freund’s adjuvant-induced–(CFA) sub-chronic and chronic paw edema treatment (p < 0.01; p < 0.01). Notably, upon oral administration of loaded IMC, animals had a significantly lower ulcer score and Paul’s Index (3.9) compared to the free drug (p < 0.05). The obtained results suggest that IMC loaded to PVP nanoparticles exhibit superior anti-inflammatory activity in vivo and a safe gastrointestinal profile and pose a therapeutic alternative for the currently available NSAIDs’ administration.

Experimental Methods for the Biological Evaluation of Nanoparticle-Based Drug Delivery Risks

“…Extensive research on new types of nanocarriers has shown that specific materials may improve the release performance. For instance, the self-assembled Amph-PVP nanoparticle was shown to successfully entrap indomethacin and deliver it to inflammatory sites, allowing for its prolonged release [ 107 ]. Similarly, 5-fluorouracil-loaded nanoparticles have shown promise as a delivery system in anticancer therapy [ 108 ], while N-vinylpyrrolidone polymer nanoparticles have been shown to be a promising drug delivery system since they are safe to use on both basal and activated endothelium [ 109 ].…”

Amphiphilic Micelles as Superior Nanocarriers in Drug Delivery: from Current Preclinical Surveys to Structural Frameworks

“…Since the overall process is driven by hydrophobic effect and is not confined to surfactant head group and the development of haphazardly mixed micellar self-associates will be likely to be favored. [34] They can be viewed as the "ideal" mixing of component in the aggregates. Moreover, in mixtures, electrostatic forces of attractions between "head" groups occur with dissimilar surfactant types and offer the foundation for the non-ideal mixing in the aggregates.…”

“…At this concentration i. e., CMC a cooperative self‐association undergoes between the surfactant molecules to form aggregates (micelles) in which the hydrophobic part of the molecules staying in the inside of the aggregates while the hydrophilic head groups are in contact to the surface with the aqueous solution (Figure 2). Since the overall process is driven by hydrophobic effect and is not confined to surfactant head group and the development of haphazardly mixed micellar self‐associates will be likely to be favored [34] . They can be viewed as the “ideal” mixing of component in the aggregates.…”

Toxicity Evaluation and Controlled-Release of Curcumin-Loaded Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles: In Vitro and In Vivo Models

“…Parameters such as the copolymer molecular weight, morphology and size of the micelles are easily controlled during the synthesis process. They can capture various therapeutic agents, such as non-steroidal anti-inflammatory drugs [ 19 , 20 , 21 ], antitumor drugs [ 22 ], antifungal antibiotics [ 23 ], cytokines [ 24 , 25 ] and plasmid DNA [ 26 ] in micelles. Depending on the average hydrodynamic radius, nanoparticles can be absorbed by cell cultures through various mechanisms, including endocytosis and membrane fusion, which allows selective delivery of the active substance to both the cell’s endosomes and its nucleus [ 27 ].…”