Bioincompatibility of Polyvinylpyrrolidone (PVP)
Polyvinylpyrrolidone (PVP) can cause significant bioincompatibility issues including complement activation, reduced transfection efficiency in drug delivery systems, and potential accumulation in tissues leading to PVP storage disease. While PVP is widely used in pharmaceutical formulations due to its water solubility and general biocompatibility, several important bioincompatibility concerns have been identified in recent research and guidelines.
Complement Activation and Immune Response
PVP has been associated with complement activation in biological systems, particularly when combined with iodine to form povidone-iodine (PVP-I) 1. This immune system activation can potentially lead to inflammatory responses in patients exposed to PVP-containing formulations.
Impact on Drug Delivery and Cellular Uptake
When used in dissolving microneedle (DMN) formulations for nucleic acid delivery, PVP demonstrates significant bioincompatibility issues:
- PVP consistently shows lower transfection efficiency compared to other polymers like PVA, with efficiency dropping to as low as 10% for high molecular weight PVP (360 kDa) versus 43% for PVA 2
- The choice of PVP as a matrix material negatively affects cellular internalization of therapeutic agents 2
- This reduced efficiency appears to be molecular weight-dependent, with higher molecular weight PVP showing worse performance 2
Pharmacokinetic Concerns and Tissue Accumulation
High-molecular-weight PVP polymers present serious bioincompatibility issues related to their retention in the body:
- These polymers cannot be excreted by the kidneys and become retained in the reticuloendothelial system 3
- This retention can lead to PVP storage disease, with clinical manifestations including:
- Bone marrow failure
- Bony destruction
- Anemia
- Pathological fractures
- Infiltration of PVP storage histiocytes in tissues 3
Impact on Blood Components
In hemodialysis applications, PVP-modified membranes show varying degrees of bioincompatibility:
- PVP elution from dialysis membranes differs between commercially available products and depends on membrane material and sterilization method 4
- Platelet loss during dialysis, a marker of biocompatibility, varies significantly with different PVP-containing dialyzers 4
- The amount of non-eluted PVP on blood-contacting surfaces appears to be an important determinant for biocompatibility 4
Nanomaterial Applications and Eryptosis
When used in nanoparticle formulations, PVP can trigger adverse biological effects:
- PVP-coated silver nanoparticles have been shown to trigger eryptosis (programmed death of red blood cells) 2
- This process occurs through calcium-dependent, reactive oxygen species (ROS)-mediated, and calpain-mediated mechanisms 2
- The eryptosis can occur even without internalization of the nanoparticles 2
Pharmaceutical Processing Considerations
In pharmaceutical manufacturing, PVP is classified as a processing aid that can function as a dispersant/surfactant (Pickering stabilizer) 2. However, its presence in final formulations may contribute to bioincompatibility issues if not properly controlled.
Clinical Implications
Healthcare providers should be aware of these bioincompatibility issues when using PVP-containing products, particularly:
- For patients undergoing repeated hemodialysis with PVP-modified membranes
- When administering PVP-containing intravenous solutions over extended periods
- When using drug delivery systems that incorporate PVP as a carrier or matrix material
- In patients with compromised immune function who might be more susceptible to complement activation
Despite these concerns, it's important to note that PVP continues to be widely used in pharmaceutical formulations due to its many beneficial properties, including water solubility, chemical stability, and general biocompatibility for most applications 5, 6, 7. The bioincompatibility issues appear to be context-specific and related to particular applications, formulations, and patient factors.