Evaluating the Efficacy of Two Osmosis-based Strategies in Red Blood Cell Drug Delivery Systems

Celia Vizan^*
*Correspondence: Celia Vizan, Department of Pharmaceutical Sciences, University of Salamanca, Salamanca, Spain, Email:

Keywords

Red blood cell • Drug delivery systems • Biocompatibility • Drugs

Introduction

One of the most well-established osmosis-based strategies for loading drugs into RBCs is the osmotic lysis and reconstitution method. This approach relies on the principle of creating an osmotic gradient to induce RBC swelling and subsequent lysis, followed by the reconstitution of the cell with the drug of interest. RBCs are suspended in a hypotonic solution, which has a lower osmolarity than the intracellular fluid of the cells. This leads to the influx of water into the RBCs, causing them to swell. The desired drug is introduced into the hypotonic solution. The drug molecules are then taken up by the resealing membrane ghosts, resulting in drug-loaded. The osmolarity of the solution is adjusted to become isotonic with the RBCs, promoting resealing and the formation of drug-loaded RBCs. Osmotic lysis and reconstitution can achieve high drug loading efficiencies, as the drug is encapsulated within the RBCs during the resealing step. Properly executed osmotic lysis and reconstitution processes have minimal impact on RBC viability, ensuring that the carrier cells remain functional in circulation. This method involves multiple steps and can be technically challenging to perform, requiring precise control of osmotic conditions [1].

Literature Review

The duration of exposure to the hypotonic solution is another critical factor. Extended exposure can lead to excessive RBC swelling, which may result in cell lysis and the release of encapsulated drugs prematurely. On the other hand, inadequate exposure may not allow for sufficient drug loading. Optimization of exposure time is essential to achieve the desired drug encapsulation efficiency. The compatibility of drugs with the hypotonic swelling process is an important consideration. Some drugs may be sensitive to the osmotic stress and the structural changes that RBCs undergo during hypotonic swelling. Therefore, thorough compatibility studies are necessary to ensure the stability and efficacy of the encapsulated drugs. Isotonic shrinkage is a less explored but equally promising osmosis-based strategy for RBC drug delivery. This method offers several advantages, including reduced cell stress and improved drug encapsulation efficiency [2].

Compared to hypotonic swelling, isotonic shrinkage imposes less stress on RBCs. By maintaining osmotic balance, RBCs experience minimal changes in shape and size during the process. This reduced stress can lead to improved cell viability and longer circulation times, making it an attractive option for drug delivery. Isotonic shrinkage allows for the formation of vesicles within the RBC membrane, providing a stable environment for drug encapsulation. These vesicles can accommodate a wide range of therapeutic agents, including hydrophobic drugs, proteins, and nanoparticles. Additionally, the controlled release of drugs from these vesicles can be achieved with precise triggers, such as changes in pH or temperature [3].

Discussion

Drug delivery systems have come a long way in improving the effectiveness and specificity of drug treatments while minimizing side effects. One promising avenue of drug delivery is harnessing the unique properties of Red Blood Cells (RBCs) as carriers for therapeutic agents. RBCs have a natural ability to traverse the circulatory system and reach distant tissues, making them an ideal choice for targeted drug delivery. Among the various approaches to enhancing RBC-based drug delivery, osmosis-based strategies have gained significant attention. In this article, we will explore and evaluate two osmosisbased strategies used in RBC drug delivery systems: hypotonic swelling and hypertonic shrinkage. These strategies exploit osmotic forces to load and release therapeutic agents within RBCs, with the aim of achieving precise drug delivery while avoiding toxicity and immune responses [4].

Hypotonic swelling is a strategy that involves exposing RBCs to a solution with a lower osmolarity than the intracellular environment. This difference in osmolarity causes water to flow into the RBCs, leading to their swelling and subsequent loading with therapeutic agents. One of the primary advantages of hypotonic swelling is its efficiency in loading therapeutic agents into RBCs. The influx of water into the cells creates temporary pores in the cell membrane, allowing for the easy entry of drugs. Hypotonic swelling typically does not cause significant damage to RBCs. The process is reversible, and RBCs can return to their normal state once exposed to an isotonic environment. Hypotonic swelling can be used to load a wide range of therapeutic agents, including small molecules, proteins, and nanoparticles. While hypotonic swelling efficiently loads therapeutic agents, it may also result in some leakage of the loaded cargo during circulation. This can reduce the overall efficacy of the drug delivery system [5].

Prolonged exposure to hypotonic conditions can stress RBCs, potentially leading to hemolysis (RBC rupture) and compromising the delivery system's safety. In contrast to hypotonic swelling, hypertonic shrinkage involves exposing RBCs to a solution with a higher osmolarity than their intracellular environment. This causes water to exit the cells, leading to their shrinkage and the encapsulation of therapeutic agents. Hypertonic shrinkage tends to retain loaded cargo more effectively compared to hypotonic swelling. The reduced volume of the RBCs minimizes the chances of cargo leakage. RBCs that have undergone hypertonic shrinkage are often more stable during circulation, reducing the risk of hemolysis and cargo release. The release of therapeutic agents from RBCs can be controlled more precisely in hypertonic shrinkagebased systems, allowing for on-demand drug delivery.

Hypertonic shrinkage requires a more intricate loading process compared to hypotonic swelling, which can make it challenging to achieve consistent results [6]. Loading efficiency in hypertonic shrinkage may be lower compared to hypotonic swelling, as the process relies on the encapsulation of drugs during cell shrinkage. Hypotonic swelling is generally more efficient in loading therapeutic agents into RBCs due to the temporary membrane pores created by osmotic influx. Hypertonic shrinkage, on the other hand, requires more controlled conditions for loading, which may result in reduced efficiency. Hypertonic shrinkage outperforms hypotonic swelling in cargo retention. The reduced cell volume in hypertonic conditions helps prevent cargo leakage during circulation. Hypertonic shrinkage provides better control over drug release, allowing for on-demand delivery. Hypotonic swelling may release cargo more readily, potentially leading to premature or erratic drug release.

Conclusion

In the quest for efficient and precise drug delivery systems, osmosisbased strategies in RBC drug delivery systems have shown promise. Hypotonic swelling offers efficient loading but may suffer from cargo leakage and potential RBC damage. Hypertonic shrinkage, on the other hand, excels in cargo retention, controlled release, and RBC stability but can be more complex to implement. The choice between these two strategies should depend on the specific requirements of the drug being delivered and the desired control over drug release. Moreover, it is essential to conduct comprehensive in vitro and in vivo studies to assess the safety, efficacy, and biocompatibility of these approaches before they can be considered for clinical applications. In the future, researchers may explore hybrid approaches that combine the strengths of both hypotonic swelling and hypertonic shrinkage to optimize drug delivery systems further. By addressing the challenges associated with each strategy, we can move closer to developing advanced RBC-based drug delivery systems that offer targeted and controlled therapeutic interventions with minimal side effects.

Acknowledgement

None.

Conflict of Interest

None.

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