Background Monoclonal antibodies (mAbs) effectively treat and prevent various diseases, but their clinical application is hindered by issues related to the route of administration and pharmacokinetics (PK). Intravenous (IV) administration is cumbersome, while subcutaneous (SC) administration is hampered by lower bioavailability and potential for immunogenicity. This study evaluated the efficacy of liposomal formulations in enhancing the subcutaneous (SC) delivery and PK of broadly neutralizing antibodies (bNAbs) directed against HIV. Methods mAbs were encapsulated in liposomes with and without PEGylation. The liposomes were characterized for particle size, polydispersity index, zeta potential, and release. Thereafter, mice were injected with free mAbs or liposome-encapsulated mAbs, and PK was evaluated. Results Liposomes exhibited sizes of 85-92 nm with negative surface charges. Encapsulation efficiencies were 61% for PEGylated and 58% for non-PEGylated liposomes. Stability testing over 16 weeks revealed that formulations remained stable at 4°C but showed leakage at 37°C. Cytotoxicity assays confirmed that the liposomal formulations did not affect cell viability or induce apoptosis in HMEC-1 cells. In vivo, PK studies in humanized FcRn mice indicated that the PEGylated formulations generally had higher half-life, Cmax, AUC, and MRT, and lower CL values compared to their non-PEGylated formulations of the same injection type. Both liposomal formulations showed improvements in bioavailability and extended half-life compared to free mAbs administered via SC and IV routes. Compared to the gold standard of IV free mAb injection, SC injection of antibodies encapsulated in PEGylated liposome had up to 80% higher bioavailability and 45% extension of half-life. Compared to the SC free mAb injection, the differences were even more pronounced, with liposomal SC injection having up to 113% higher bioavailability and 81% extension of half-life. Conclusion Overall, liposomal encapsulation effectively protected SC injected mAbs from degradation, facilitated sustained release, and improved PK profiles, suggesting a promising strategy for enhancing the therapeutic potential of mAbs in conditions that need repeated injections. Future work should further optimize liposomal formulations to increase loading capacity, stability, and release kinetics. STATEMENT OF SIGNIFICANCE: This study addresses a challenge in the administration of monoclonal antibodies (mAbs). Intravenous administration requires additional resources, including nursing staff, making it time-consuming and costly. Although subcutaneous (SC) administration offers a less expensive and more patient-friendly option, it suffers from lower bioavailability and potentially shorter half-life. In this study, we encapsulated mAbs in liposomal formulations specifically designed to enhance their pharmacokinetics by promoting efficient lymphatic transport. Compared with both SC and even IV administration of free antibodies, liposomal formulations of mAbs remarkably improve bioavailability and extend the half-life. This innovative approach combines the comfort of SC administration with enhanced pharmacokinetics, addressing the limitations of current SC delivery methods. Liposomal formulations have the ability to greatly improve SC mAb administration by reducing the amount of antibody needed to be administered, reducing the frequency of injections, and potentially protecting against immunogenicity.