The treatment of human diseases relies on the therapeutic effect achieved by the pharmaceutical compound administered within the body as a drug. These drug delivery systems (DDS) ensure that the drug reaches its targeted site and perform its function by causing no side effects or progression in the neighboring organs. The system formulates the drug molecules in forms which work in accordance to the patient and provide better bioavailability. Oral formulations like pills and syrup, topical such as gels and creams for the skin, parenteral routes of injections, nasal sprays, ocular drops and transdermal patches that release drugs through the skin, are various forms of administration that come under DDS. But as advances in scientific research happen every day, a mere shift from these conventional to the novel methods of drug delivery might not only provide enhanced techniques for drug stability but also intricate methods that meet the challenges of the former one with their increased automation. Advances in understanding the pharmacokinetics and pharmacodynamic parameters resulted in designing better drug delivery systems demonstrating the impact of drug release in influencing the effectiveness of treatment (Vargason et al., 2021). Tablets, the most widely used delivery system, though effective, poses a challenge in the form of asphyxiation, hepatic first-pass metabolism and altered rate of drug release due to its formulation methods. Moreover, it is not possible to achieve a targeted delivery of the drugs through the conventional formulations such as peroral and parenteral. Nanoparticles came to the rescue for issues such as targeting the drug, increasing the bioavailability, or reducing the drug-induced toxicities. Liposomes were the first nanoparticle to be developed in the 1960s which paved the way for novel drug delivery system or NDDS (Ezike et al., 2023). They have the advantage of providing expanded efficacy, solubility, permeability and specific targeting of the drug molecules over the traditional forms. Liposomes and other lipid nanoparticles such as solid lipid nanoparticles are being used for efficient, targeted, and sustained release systems ensuring the maintenance of effective therapeutic drug concentration (Bummer, 2004, Tiwari et al., 2012). In liposome-based formulation, a drug is encapsulated within a phospholipid bilayer structure to improve its therapeutic efficacy and bioavailability. Liposomes are further coated with hydrophilic polymers, such as Poly-Ethylene Glycol or PEG, to minimise the phagocytic clearance of the particles inside the human body. Such liposomes are known as stealth liposomes. Further, tissue-specific or cell-specific ligands are attached on to the liposomal surface for a targeted delivery of the therapeutic drug to the site (Bummer, 2004). The ligand could be a monoclonal antibody or antibody fragment facilitating the transition of liposome to particular targets that enhances the receptor mediated endocytosis. Such liposomes, known as immunoliposomes, carry the drug to cells that express a particular antigen. For example, anti-HER2 antibodies or antibody fragments can be used over the lipid nanoparticle’s surface to deliver the anti-cancer drug targeted to the tissue overexpressing HER-2 (Bummer, 2004, Pande, 2023). Liposomes and solid lipid nanoparticles have been clinically used to deliver small molecule drugs and nucleic acid-based drugs/antigenic segments. Thermoplastic aliphatic polyesters like poly-lactic acid (PLA) and poly-L-lactic-co-glycolic acid (PLGA) are two widely used polymers that received approval from the US Food and Drug Administration (FDA) for biomedical applications. They have attracted a lot of attention among various classes of biodegradable polymers due to their simple construction into different formulations that transport therapeutic drugs, including macromolecules such as proteins, peptides, and vaccines (Patra et al., 2018, Saroja et al., 2011). The delivery of drugs via exosomes is a novel and promising method of targeted therapy that utilizes their natural biological properties. They are ideal for delivering drugs like small molecules, RNA and proteins due to their biocompatibility, low immunogenicity and ability to cross biological barriers, including the blood-brain barrier. Exosomes can also be customised with surface ligands to enhance their targeting of diseased organs, thereby improving therapeutic efficacy while reducing off-target toxicities. Currently, research is focused on optimizing methods for isolating exosomes, loading cargo into them, and decorating their surfaces to enhance their clinical application potential (Kim et al., 2024).

Oral and parenteral routes are the most widely used routes of drug administration, employing delivery systems such as tablets, capsules, and injections. These delivery systems, while effective and widely used, are often hindered by reduced bioavailability (in case of oral route) and lack of specific targeting (in case of parenteral routes). These limitations lead to fluctuations in drug levels, the risk of sub-therapeutic or toxic effects, and necessitate frequent dosing, which may compromise patient compliance and safety. Additionally, indiscriminate distribution can cause undesirable side effects and potential toxicity in off-target tissues, restricting the therapeutic accuracy of treatment. These persistent challenges drive the ongoing evolution and innovation of advanced drug delivery technologies (Vargason et al., 2021; Vllasaliu, 2025). Vaccines, on the other hand, are primarily administered intra-muscularly. Though the intra-muscular (IM) route has various benefits both in terms of easily accessible site and immunological competency, the most widely reported adverse effect of IM delivery is peripheral nerve injury (Desai et al., 2019). With the advancements in biotechnology, novel vaccines and vaccine platforms such as subunit vaccines, conjugated vaccines, virus-like particles etc., have a further restriction for parenteral administration as oral administration may degrade the antigenic candidates through proteolytic system of the gut (Vllasaliu, 2025).