Drug Delivery via Liposomes for Oral Diseases: Mechanisms, Applications, and Challenges

by drbyos

Introduction

Oral diseases pose a significant global health challenge, affecting millions worldwide. Traditional treatments often fall short due to poor retention, high side effects, and inefficacy. However, a novel approach using liposomes as drug delivery vehicles is revolutionizing this field. These tiny lipid vesicles, ranging from 50 to 500 nm in diameter, offer a promising solution by encapsulating therapeutic compounds and enhancing their efficacy and delivery.

Drug Delivery via Liposomes

Liposomes consist of a bilayer composed of natural or synthetic lipids, forming spherical vesicles that can encapsulate both hydrophobic and hydrophilic drugs. This dual encapsulation capability increases their therapeutic index. Various methods, including thin-film hydration, solvent injection, and microfluidic channels, are used to prepare liposomes. They reduce drug toxicity and enhance delivery to target tissues by modifying pharmacokinetics and biodistribution.

Figure 1 Liposome Structure. Created in BioRender. Suliman, K. (2024) BioRender.com/z34c794.

Sterically stabilized liposomes, incorporating hydrophilic polymers like polyethylene glycol (PEG), improve circulation time and stability, making them ideal for targeted delivery.

Figure 2 Liposome as Drug Delivery Carrier (A); Mechanism Action of Liposome (B). Created in BioRender. Suliman, K. (2024) https://BioRender.com/ x84r388.

Liposome Internalization Mechanisms

Liposomes can be internalized through endocytosis or direct membrane fusion. Endocytosis involves engulfing the liposome by the cell membrane, forming vesicles. This pathway includes several routes: clathrin-mediated, caveolin-mediated, micropinocytosis, and intracellular inflammatory pathways. Direct membrane fusion bypasses the endo-lysosomal pathway, delivering drugs directly into the cytosol.

Various factors influence these mechanisms, such as cell surface receptors and liposome characteristics. Environmental acidity and lipid composition significantly impact fusion rates.

Advancements in Liposomes for Oral Disease Therapy

Research on liposomes for oral diseases has progressed, evolving from conventional formulations to advanced designs like polymer-grafted and polymer-coated liposomes.

Figure 3 Advancement of Liposome. Created in BioRender. Suliman, K. (2024) BioRender.com/x30d074.

Conventional Liposomes

Conventional liposomes consist of zwitterionic phospholipids and cholesterol, providing essential structure and stability. They improve drug retention and efficacy in the oral cavity.

Studies by Yamakami et al and Saadat et al demonstrated the effectiveness of conventional liposomes in suppressing bacterial biofilms and enhancing drug delivery.

Polymer-Coated Liposomes

Polymer coatings enhance liposome stability by reducing vesicle fusion and leakage. Common coating methods include one-layer polymer coating, layer-by-layer (LBL) coating, and cross-linked polymer coating.

One-Layer Polymers

Chitosan, a mucoadhesive polymer, enhances liposome stability and retention time in the oral cavity, providing sustained drug delivery.

Layer-By-Layer Polymers

LBL coating techniques use charged polymers like chitosan and alginate to layer liposomes, creating stable liposomal systems with enhanced protection.

Cross-Linked Polymers

Cross-linking polymer-coated liposomes, such as those in a chitosan-based buccal film containing atorvastatin, enhance structural integrity and stability.

Polymer-Grafted Liposomes

These liposomes incorporate polymers directly into their bilayer, improving stability and drug-loading capacity. PEGylation is a common modification, extending circulation time and reducing mononuclear phagocyte system uptake.

PEGylated Liposomes

PEGylation enhances liposome penetration through the oral mucosa, improving drug delivery and bioavailability.

Targeted Liposomes

Targeted liposomes, modified with specific ligands, enhance drug accumulation in target cells, reducing side effects and improving efficacy.

Studies by Yang et al and Wijetunge et al demonstrated the targeted delivery of drugs like ursolic acid and quranoliposomes for oral conditions.

Stimuli-Responsive Liposomes

These liposomes respond to external stimuli, such as changes in pH, releasing drugs precisely when and where needed, enhancing therapeutic outcomes.

Role of Liposomes in Oral Disease Therapy

Liposomes have been studied extensively for treating various oral diseases, including candidiasis, oral cancer, infections, lesions, dental caries, and periodontitis.

Figure 4 Role of Liposome in Oral Diseases Therapy. Created in BioRender. Suliman, K. (2024) BioRender.com/a09n546.

Treatment of Fungal Infections

Studies demonstrate that liposomes encapsulating antifungal agents like amphotericin B, nystatin, and trans-caryophyllene provide superior antifungal efficacy compared to free drugs.

Treatment of Bacterial Infections

Liposomes containing nisin can inhibit glucan biofilm synthesis by cariogenic bacteria, reducing dental caries risk.

Treatment of Oral Lesions

Liposomes loaded with bioadhesive polymers and drugs like amoxicillin provide targeted and sustained drug delivery for oral ulcers, reducing tissue damage.

Treatment of Oral Cancer

RNA-coated liposomes and targeted formulations reduce tumor volume effectively, minimizing side effects on healthy tissues.

Clinical Applications

Commercial liposome-based drugs like Ambisome® and Nyotran® demonstrate the effectiveness and market potential of liposomal formulations for fungal infections in immunocompromised patients.

Challenges in Liposome Development

Despite their potential, liposomes face challenges in stability, large-scale manufacturing, and regulatory approval. Research focuses on overcoming these hurdles to enhance clinical application.

Future Directions

Future advancements aim to improve liposome stability and bioavailability, targeting specific cell types, and overcoming current limitations.

Conclusion

Liposomes represent a promising approach to treating oral diseases, offering enhanced drug efficacy, stability, and targeted delivery. Ongoing research will likely expand their clinical applications, improving patient quality of life.

Do you have any questions about liposomes and their role in oral disease therapy? Let us know in the comments below!

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