Opportunistic infections are widespread in HIV infected and other immunosuppressed individuals. Cochleate cylinders are an innovative and relatively new lipid based delivery system. The long term goals of this research program are to determine the feasibility and technical merit of drug-cochleate formulations to enhance the efficacy of some currently available antimicrobials by increasing therapeutic index and patient compliance. The present application will focus on investigating the properties of Amphotericin B cochleate formulations on the growth of the microorganisms in vitro and in vivo. Achieving efficacious oral delivery for systemic infections is a major emphasis of the present application. The following specific aims will be investigated: I. Formulation development to maximize oral delivery of Amphotericin B. II. Determine the toxicity, pharmacokinetics and biodistribution of AmB- cochleate formulations in vivo. III. Extend the in vivo protection of AmB-cochleates delivered systemically into an Aspergillus/rat model. IV. Investigate the in vivo efficacy of orally delivered AmB cochleates in the Candida/mouse and Aspergillus/rat models. The strategy is to continue and expand on ongoing collaboration among three established investigators with different but overlapping and complementary areas of scientific expertise. In addition, this collaboration combines the technology and resources of a recently established biotechnology company and an internationally recognized research institute.
The long term commercial goals are to develop drug-cochleate formulations which will enhance the efficacy of some currently available antimicrobials by increasing the therapeutic index, (decreasing toxicity and decreasing the minimal inhibitory dose), and increasing patient compliance, (by decreasing the dosing regime and improving routes of delivery). The present application will focus on investigating the properties of Amphotricin B cochleate formulations on the growth of the microorganisms in vitro and in vivo. Positive results in these studies will provide the rationale for future Phase II studies.
| Zarif, Leila (2002) Elongated supramolecular assemblies in drug delivery. J Control Release 81:7-23 |
| Delmas, G; Park, S; Chen, Z W et al. (2002) Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis. Antimicrob Agents Chemother 46:2704-7 |
| Santangelo, R; Paderu, P; Delmas, G et al. (2000) Efficacy of oral cochleate-amphotericin B in a mouse model of systemic candidiasis. Antimicrob Agents Chemother 44:2356-60 |
