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.

After the COVID-19 pandemic, mRNA-based vaccines have emerged as a revolutionary technology in immunization and vaccination. These vaccines have shown remarkable efficacy against the virus and opened up avenues for their possible application in other diseases. This has renewed interest and investment in mRNA vaccine research and development, attracting the scientific community to explore all its other applications beyond infectious diseases. Recently, researchers have focused on the possibility of adapting this vaccination approach to cancer immunotherapy. While there is a huge potential, challenges still remain in the design and optimization of the synthetic mRNA molecules and the lipid nanoparticle delivery system required to ensure the adequate elicitation of the immune response and the successful eradication of tumors. This review points out the basic mechanisms of mRNA-LNP vaccines in cancer immunotherapy and recent approaches in mRNA vaccine design. This review displays the current mRNA modifications and lipid nanoparticle components and how these factors affect vaccine efficacy. Furthermore, this review discusses the future directions and clinical applications of mRNA-LNP vaccines in cancer treatment.

Background: The oral delivery of biopharmaceuticals remains a major challenge for researchers and the pharmaceutical industry. Therefore, extensive research is ongoing to develop a viable delivery method, hence self-emulsifying drug delivery systems (SEDDSs) are being investigated because of their ability to protect the carried macromolecules in the gastrointestinal environment and facilitate absorption through the intestinal barrier. Objectives: To systematically investigate this promising method for the oral delivery of lysozyme (LYZ) and to model oral peptide/protein administration. Methods: LYZ/sodium dodecyl sulfate (SDS) hydrophobic ion pairs (HIPs) were prepared to enhance protein solubility and stability in SEDDSs. Different surfactants (Tween^® 20 and 80) and as co-surfactants (Span^® 20 and 80) were combined for the preparation of liquid SEDDSs according to a 2² full factorial design and samples of each combination were formulated based on a three-factor-constrained mixture design. The critical quality attributes (CQAs), droplet size, polydispersity index (PDI), and zeta potential were measured by dynamic light scattering (DLS). The process design space was determined by response surface methodology (RSM) and two-dimensional ternary contour plots. An in vitro release test was performed using the sample-and-separate approach. Results: Emulsions of SEDDSs with the optimal properties of droplet size < 200 nm, PDI < 0.4 and zeta potential < −10 mV were prepared. Consequently, a HIP load of 10 mg/g was achievable, exhibiting apparent first-order kinetics, with approximately 80% of the loaded LYZ released within 6 h. Conclusions: This study may contribute to better understanding of the effects and interactions of formulating materials for SEDDSs and their possible role in the oral delivery of biopharmaceuticals.