Currently, pharmaceutical companies are working on innovative methods, processes and products. Oral mucoadhesive systems, such as tablets, gels, and polymer films, are among these possible products. Oral mucoadhesive systems possess many advantages, including the possibility to be applied in swallowing problems. The present study focused on formulating buccal mucoadhesive polymer films and investigating the physical and physical–chemical properties of films. Sodium alginate (SA) and hydroxypropyl methylcellulose (HPMC) were used as film-forming agents, glycerol (GLY) was added as a plasticizer, and cetirizine dihydrochloride (CTZ) was used as an active pharmaceutical ingredient (API). The polymer films were prepared at room temperature with the solvent casting method by mixed two-level and three-level factorial designs. The thickness, tensile strength (hardness), mucoadhesivity, surface free energy (SFE), FTIR, and Raman spectra, as well as the dissolution of the prepared films, were investigated. The investigations showed that GLY can reduce the mucoadhesivity of films, and CTZ can increase the tensile strength of films. The distribution of CTZ proved to be homogeneous in the films. The API could dissolve completely from all the films. We can conclude that polymer films with 1% and 3% GLY concentrations are appropriate to be formulated for application on the buccal mucosa as a drug delivery system.

Vaginal drug delivery systems can provide a long-term and constant liberation of the active pharmaceutical ingredient even for months. For our experiment, FDM 3D printing was used to manufacture the vaginal ring samples from thermoplastic polyurethane filament, which enables fast manufacturing of complex, personalized medications. 3D printing can be an excellent alternative instead of industrial manufacturing, which is complicated and time-consuming. In our work, the 3D printed vaginal rings were filled manually with jellified metronidazole or chloramphenicol for the treatment of bacterial vaginosis. The need for manual filling was certified by the thermogravimetric and heatflow assay results. The manufactured samples were analyzed by an Erweka USP type II Dissolution Apparatus, and the dissolution profile can be distinguished based on the applied jellifying agents and the API’s. All samples were considered non-similar based on the pairwise comparison. The biocompatibility properties were determined by prolonged MTT assay on HeLa cells, and the polymer could be considered non-toxic. Based on the microbiological assay on E. coli metronidazole and chitosan containing samples had bactericidal effects while just metronidazole or just chitosan containing samples bacteriostatic effect. None of these samples showed a fungistatic or fungicide effect against C. albicans. Based on our results, we successfully manufactured 3D printed vaginal rings filled with jellified metronidazole.

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research.