title: Release Characteristics In Vitro and In Vivo of In Situ Gels for a Novel Peptide Compared with Low-Molecular-Weight Hydrophilic Drug.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Guiying
authors.initials: G
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Meng
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Lijun
authors.initials: L
authors.lastname: Gao
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China.
authors.forename: Dongqin
authors.initials: D
authors.lastname: Quan
mesh_terms: D016503:Drug Delivery Systems; D065546:Drug Liberation; D005782:Gels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D009271:Naltrexone / Q000008:administration & dosage* / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D013696:Temperature
chemical_list: D005782:Gels; C514029:LXT-101; D009842:Oligopeptides; D010455:Peptides; D009271:Naltrexone
keywords: In situ gels; LXT-101; PLGA-PEG-PLGA; pharmacodynamics; pharmacokinetics; releasing; temperature-sensitive