Lipospheres of benzyl penicillin were formulated using the conventional thin film hydration technique. Five different combinations of shea butter, surfactant (Span 80) and goat fat were the key variables employed in the formulations. The resultant lipospheres were evaluated with respect to surface morphology, particle size distribution, encapsulation efficiency, in vitro drug release, in vivo bioavailability and in vitro antimicrobial activity. Particle size was found to increase with increased drug loading, the average particle radius of the batches being 12.5 nm. The encapsulation efficiency was found to be high at all levels with encouraging values of 80.21 and 83.44 % for batch A and E respectively, with batch A containing shea butter and span 80 in the ratio of 1:1 and batch E containing shea butter, span 80 and goat fat in the ratio of 1:2:1. Batch A appear to exhibit sustained release in vitro with cumulative drug release being 60 % while batch E has a cumulative drug release of 98 % respectively. The presence of goat fat however seems to impact negatively on the in vivo stability of batch E liposphere. The test microorganisms showed sensitivity to the two batches in marked contrast to the uncapsulated benzyl penicillin especially against the multiple-antibiotic resistant strains of S. typhi, P. vulgaris and P. aereuginosa used in the study.