LIPOSPHERE LOCAL-ANESTHETIC TIMED-RELEASE FOR PERINEURAL SITE APPLICATION

Purpose. This investigation determines the drug delivery capacity of L ipospheres, which are drug-containing solid-filled vesicles made of tr iglyceride with a phospholipid outer covering, to release local anesth etic in vitro and to produce sustained peripheral nerve block in vivo. Methods. The local anesthetic, bupivacaine, was loaded into Lipospher es in several dosage forms, characterized, and measured for in vitro r elease. In rats, Lipospheres were administered into a large space betw een muscle layers surrounding the sciatic nerve to assess sensory and motor block in vivo. Results. The particle size of Lipospheres was det ermined to be between 5 and 15 mu m, with over 90% surface phospholopi d. Lipospheres released bupivacaine over two days under ideal sink con ditions. Liposphere nerve application produced dose-dependent and reve rsible block. Indeed, sustained local anesthetic block (SLAB) was obse rved for 1-3 days in various in viva tests: a) Wind paw withdrawal lat ency to noxious heat was increased over 50% for 96 hr period after app lication of 3.6% or 5.6% bupivacaine-Lipospheres. The 3.6% and 5.6% do ses were estimated to release bupivacaine at 200 and 311 mu g drug/ hr , respectively, based on release spanning 72 hr. Application of 1.6% b upivacaine-Lipospheres increased withdraw latency 25-250% but for only a 24 hr duration; b) Similarly vocalization threshold to hind paw sti mulation was increased 25-50% for 72 hr following application of 3.6% bupivacaine-Lipospheres; c) Finally, sensory blockade outlasted or equ aled corresponding motor block duration for all Liposphere drug dosage s. Conclusions. Liposphere delivery of local anesthetic drugs may be w ell suited for site-specific pharmacotherapy of neural tissue to produ ce SLAB. Dose-dependent effects in duration of action may include lipo philic tissue storage.