The key to successful vaccination is to administer and deliver vaccines in a way that evokes strong immune responses. Due to technological advancements and immunological perspectives, modern vaccine delivery relies on nanoparticle-based platform technologies. Nanotechnology application in vaccine drug delivery has led to significant progress in vaccine development. New vaccine delivery systems enhance immunogenicity and efficacy, overcoming the limitations of conventional vaccines.

Apart from the formulation and delivery systems, dosage and route of administration also have an impact on the safety and efficacy of the vaccines. Vaccines can be administered by multiple routes, including intramuscular, subcutaneous, transdermal, oral inhalation, and nasal mucosa. Let’s look at the various vaccine delivery systems.

Virus-like particles and virosomes

Virus-like particles (VLPs) are nanostructures with self-assembling shells consisting of one or more structural proteins derived from the virus coat or envelope. The VLP mimics the form and size of their parent virus but is devoid of genetic material, making it incapable of infection or replication. It is highly immunogenic and is able to elicit both antibody- and cell-mediated immune responses. It ranges in size from 80 to 150 nm and possesses the ability to present multiple proteins to the immune system.

The VLP membrane consists of viral phospholipids and glycoproteins; it has an empty core that transports antigens. Based on structure, VLPs are classified into enveloped and non-enveloped VLPs. Depending on the virus source, VLPs self-assemble to form a variety of shapes and structures. VLP vaccines are used to protect against the hepatitis B virus (HBV) and human papillomavirus (HPV) infections. The formulation of a vaccine consists of a vaccine vector, adjuvants, and excipients. Excipients such as buffers, stabilizers, and preservatives improve the physical and chemical stability of VLPs and prevent enzymatic degradation. Optimization of buffer pH and ionic strength are important for formulating a stable, liquid VLP vaccine. Cryoprotectants like trehalose, sucrose, and glycerol improve the formulation stability. Freeze-drying or lyophilization can enhance the shelf-life stability of VLPs. The majority of the commercial VLP vaccines are available in liquid suspension form.

Virosomes, which resemble liposomes, serve as vesicles for encapsulating DNA. Virosomes contain viral envelope proteins to fuse with target cells and subsequent DNA delivery into the cells. They act as a vaccine adjuvant, as a delivery vehicle for peptides, nucleic acids, and proteins, and as drug targeting. The virosome-mediated vaccine delivery system is used in the treatment against Ebola, hemorrhagic fever, and HIV.

Polymeric nanoparticles

Polymeric nanoparticles are solid colloidal particles within the size range of 1 to 1000 nm. They are made up of biodegradable and biocompatible polymers where active compounds can be entrapped or encapsulated in a carrier or surface-adsorbed onto the polymeric core. Based on morphology, nanoparticles are categorized into nanocapsules and nanospheres. Selection of the right polymer (either natural or synthetic) may enhance antigen stability, influence release kinetics, and elicit an immune response. Benefits of the polymerbased delivery system include its adjuvant effects, resistance to enzymatic and environmental degradation, and delayed release. Physiochemical properties, including size, shape, charge, and hydrophobicity, of polymeric nanoparticles have an effect on their delivery and uptake. Polymers are nontoxic, biocompatible, and biodegradable materials. 

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