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Controlled Release Patterns of Liposomal Bupivacaine after Neuraxial Administration in Rats
Abstract Number: S-14
Abstract Type: Original Research
Objectives: In vitro slow releasing pattern of liposomal bupivacaine compared to non-liposomal bupivacaine in the artificial cerebrospinal fluid has been demonstrated previously (1). Therefore, we aimed to evaluate the in vivo effect of intrathecal administration of liposomal bupivacaine on the duration of analgesia and the motor block in rats.
Methods: After approval of the IRB for laboratory studies, bupivacaine HCl (BHCl), bupivacaine base, cholesterol, dipalmitoyl phosphatidylcholine and methanole were distillated with vacuum in rotavapor device. They were kept in an ultrasound bath to achive homogenic distribution. Two different liposomal bupivacaine formulations were made as liposomal bupivacaine (LB) and High Yield Drug Entrapment in Liposome (HYDEL) (2). Three groups consisting of 6 rats were assigned as Group 1 (BHCl), Group 2 (LB), Group 3 (HYDEL). Anesthesia induction was provided with sevoflurane inhalation at low concentrations that may allow awakening within approximately 3 minutes (min). Local anesthetic formulations were injected into the intrathecal space in volume of 30 µl (0.5 % BHCL) at lumbar region after achieving a positive indication of electrical shock-like tail movement and analgesia was assessed using the tail flick test while motor block degree was scored (0: Complete motor block, 1: Partial motor block, 2: No motor block) as described (3,4).
Results: Tail-flick latencies significantly prolonged with (HYDEL) compared to BHCl after 150 min of injection (p<0.05). The prolongation of tail flick latencies in BHCl and LB groups have lost their significance after 60 min though the prolongation has stayed for 150 min. in HYDEL group (p<0.05) (figure 1). Complete or partial motor block (0 or 1 st degree) decreased to zero in 75 min in the BHCL group but it declined to zero after 20 min in LB and HYDEL groups.
Conclusions: Controlled-release pattern was observed after intrathecal administration of HYDEL bupivacaine in rats. The longer duration of antinociceptive activity in HYDEL than bupivacaine alone without prolonging the motor block might be promising in obstetric anesthesia after further human studies.
1. Duzlu A, Gunaydin B, Sukuroglu M, Degim T. SOAP 2013; Abstract F20
2.Degim IT et al. J Nanosci Nanotech 2006
3. Kanai Y et al . Reg Anesth Pain Med 1999
4. Morimoto K et al. J Vet Med 2001; A 48