Developments in nanoscience and nanotechnology during the last three decades have provided tremendous progress in designing nanostructures of various materials, shapes, sizes, and properties [[1], [2], [3], [4], [5], [6]]. Although the term ‘nano’ was first used about 6 decades ago, the significance of nanoscience is still prevalent and growing at a fast pace. The role of nanoscience in combating the recent global pandemic caused by coronavirus disease 2019 (COVID-19) has been praiseworthy, especially for its contribution in developing detection tools and vaccine design [[7], [8], [9]]. Polymers are among the most frequently used materials used for designing such nanostructures. Polymeric nanoparticles have gained increasing attention due to their applications in countless fields such as healthcare, electronics, renewable energy, security, food science, cosmetics, pollution control, forensic science, etc. [[10], [11], [12], [13], [14]]. Due to the unique properties of polymer nanoparticles, they are utilized in almost every sector of our daily lives. Various research groups have vested their interests in designing these nanoparticles as seen through the rising number of research articles published annually (Fig. 1a). These nanoparticles are being increasingly exploited for nanocarrier design; thus, it is necessary to have a clear understanding of how such nanocarriers are designed, what interactions dictate their formation, and the fate of their therapeutic payloads.

The properties of polymer nanoparticles depend on particle size, morphology, polymer functionality, etc. [15,16]. The size and morphology of polymer nanoparticles depend not only on the experimental conditions used during their fabrication but also on the method selected to design them. In pharmaceutical industries, polymer nanoparticles are often used as polymeric nanocarriers (PNCs) and are mostly utilized for therapeutic delivery, bioimaging, and disease diagnosis [[17], [18], [19]]. To achieve a particular objective in the pharmaceutical industry, these PNCs can be tuned to exhibit specific properties, such as target specificity, loading and delivery efficacy, protection of cargo, etc. [[20], [21], [22]]. Thus, it is important to design such nanocarriers to modulate their properties according to the demand of a particular application [23]. As a result, selecting an appropriate fabrication method and optimizing the experimental parameters are crucial [24]. There are several reviews on the design of PNCs, however, they are scattered in various literature and primarily address a particular method and/or target in each review [1,[25], [26], [27]]. The majority of such individual reviews mostly focus on techniques like emulsion and precipitation, while reviews on gelation, dialysis, salting out, molecular imprinting, etc. are underrepresented [[28], [29], [30]]. Additionally, there is also a gap in reviewing the roles of various experimental conditions and the mechanistic pathways followed during the fabrication of these PNCs.

The objective of this review is to compile and assess the methods used to design PNCs for drug delivery and the influence of experimental conditions to control particle size and morphology. Additionally, PNCs must overcome numerous biological barriers, such as the blood-brain barrier [[31], [32], [33], [34]], skin [35,36], mucosa [37], etc., highlighting the need for careful and precise fabrication. This paper delineates the design strategies utilized across various fabrication techniques, scrutinizes the influence of experimental parameters on attaining targeted shapes and sizes, and explores future perspectives that could shape advancements in this field.