Efficacy of Liposome-Encapsulated Doxycycline Against Methicillin-Resistant Staphylococcus aureus

Introduction: Antibiotic-resistant bacterial infections pose a growing global health threat and are projected to become the leading cause of mortality by 2050. Staphylococcus aureus (S. aureus), a common antibiotic-resistant pathogen, colonizes approximately two billion people, with 53 million carrying methicillin-resistant S. aureus (MRSA). The increasing prevalence of MRSA presents treatment challenges, particularly in resource-limited settings. In Mongolia, antibiotic consumption reached 40.48 defined daily doses (DDDs) per 1000 inhabitants per day in 2020, underscoring the need for alternative therapies. This study aimed to encapsulate doxycycline in liposomes and evaluate its antibacterial efficacy against S. aureus and MRSA.

Methods: Phospholipids were extracted from egg yolk and analyzed by thin-layer chromatography (TLC). Liposomes were prepared using the thin-film hydration technique with freeze–thaw cycles. Atomic force microscopy (AFM) characterized liposome morphology and size, while high-performance liquid chromatography (HPLC) quantified doxycycline content. The minimum inhibitory concentration (MIC) of liposome-encapsulated doxycycline was determined via broth microdilution assays against S. aureus and MRSA.

Results: Phospholipid extraction yielded 32%, with TLC confirming phosphatidylcholine presence. AFM revealed an average liposome height of 41.15 nm (±4.9 nm) and a diameter of 153.07 nm (±70.48 nm), with a polydispersity index of 0.212. HPLC showed a retention time of 5.843 minutes, confirming high doxycycline purity (981 ppm). MIC values for free doxycycline against S. aureus and MRSA were 8 μg/mL and 32 μg/mL, respectively, whereas liposome-encapsulated doxycycline reduced MIC to 4 μg/mL (S. aureus) and 16 μg/mL (MRSA).

Conclusion: Liposomes with an average diameter of 153 nm were successfully produced. Encapsulated doxycycline demonstrated enhanced antibacterial activity, reducing MIC values by 50% for both S. aureus and MRSA compared to free doxycycline. These findings highlight liposomal drug delivery as a promising approach for combating antibiotic-resistant infections.