Background: The thermo-sensitive in situ gels based on copolymers are attractive as an injectable
drug delivery carriers for sustained releasing of hydrophilic drugs. The purposes of this work
are to investigate the release behavior in vitro and pharmacokinetic profiles in vivo of peptide and lowmolecular-
weight hydrophilic drug loaded in the in situ gels.
Methods: A triblock copolymer PLGA-PEG-PLGA (1402-1000-1402) 1115A (1115A) was synthesized
and its rheological and gelatin properties were evaluated. The temperature-sensitive in situ gels based
on 1115A of LXT-101, a polypeptide drug, were prepared and the release characteristics in vitro and
pharmacokinetic behavior in vivo were investigated. Meanwhile, naltrexone hydrochloride (NTX), a
water-soluble low-molecular-weight drug was chosen as the model drug and the in situ gels were also
prepared and studied comparatively.
Results: Slow-release characteristics were observed in vitro with in situ gels of LXT-101 and NTX. The
release profiles and the mechanisms were different manifested by that NTX was released from in situ
gels faster and more completely than LXT-101. Otherwise, the release pattern of LXT-101 showed a
biphasic mechanism, an initial Fickian diffusion followed by a combination of degradation and diffusion
at a later stage. The results of pharmacokinetic study indicated that a sustained release behavior
could be obtained with MRT0-t (30.34 ± 12.47) h for LXT-101 and MRT0-t (2.37 ± 0.876) h for NTX,
about 10 and 4 times longer than those of aqueous solution respectively. The pharmacodynamics studies
in vivo further showed that in situ gel formulations of LXT-101 could sustain efficacy 6 days compared
with only 1 day for aqueous solutions.
Conclusion: The results of release behavior in vitro and in vivo indicated that in situ gels with copolymer
1115A could be served as carriers for delay-released drug delivery systems and might be more suitable
for polypeptide drugs compared to low-molecular-weight hydrophilic drugs.