**7. Conclusions**

In this review, a comprehensive description of the theoretical and practical aspects behind the production of di fferent polysaccharide-based hydrogel particles (PbHPs) by prilling technology in tandem with several curing technique is given. PbHPs, depending on the designed characteristics, can be produced as drug delivery systems exerting a number of functions as to control drug release and targeting. Beads with modular inner structure and tailored texture (xerogel, aerogel, cryogel) and with di fferent configurations (mono-layered "only core" or multi-layered "core-shell") may be obtained by a proper selection of the droplet formation technique and the subsequent gelation step. However, the choice of the drying method for the hydrogel is a critical step allowing to obtain carriers with specific morphology and inner structure and hence with controlled release properties, mainly of anti-inflammatory and antibiotic drugs.

Several studies in literature highlight that prilling is a versatile technique to develop polysaccharidebased particles loaded with di fferent drugs (i.e., NSAIDs and SAIDs), both with poor and high solubility, intended for oral or topical applications and intended as fast or prolonged/sustained drug release formulations. The added value of this technique is related to its versatility and scalability. In fact, such technique is already approved for large scale by some companies. In general, the pathway for PbHP production through prilling comprises a deep knowledge of various formulation and process parameters, starting from biopolymer concentration, type of solvent, feed solution viscosity, gelling methods and properties of cation or cations for ionotropic gelation. Moreover, drying conditions play an important role in determining the characteristics of the final material.

Despite the promising pharmaceutical applications, these are some challenges correlated to the numerous critical parameters influencing size, shape, morphology and structure (i.e., homogeneity, density, strength, flexibility, pore size, permeability) of the final material and hence the release profile of the entrapped drug and its in vivo activity. The possibility to apply the Design of Experiment for the development of PbHPs and the use of artificial intelligent (AI) tools for the process optimization may reduce the time and make more e fficient the process design. Another important aspect to consider is the possibility of including safety in the design of PbHPs as useful tool to enhance the medical translation of such innovative DDS.

**Author Contributions:** All authors contributed equally to this paper. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by: -Regione Campania Italy—POR Campania FESR 2014-2020 Technology Platform for Therapeutic Strategies Against Resistant Cancer Project "Campania Oncoterapie", Combattere la Resistenza Tumorale: Piattaforma Integrata Multidisciplinare per un Approccio Tecnologico Innovativo alle Oncoterapie. -Xunta de Galicia [ED431F 2016/010], MCIUN [RTI2018-094131-A-I00], Agrupación Estratégica de Materiales [AeMAT-BIOMEDCO2, ED431E 2018/08], Agencia Estatal de Investigación [AEI] and FEDER funds.

**Acknowledgments:** C.A. García-González acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239].

**Conflicts of Interest:** The authors declare no conflict of interest.
