Some biguanides can cross the mitochondrial

Some biguanides can cross the mitochondrial membrane and increase L-lactate formation by inhibiting oxidative NG,NG-dimethyl-L-Arginine hydrochloride [34]. On the other hand, it has also been reported that levels of fasting plasma lactate in T2DM patients are similar regardless of whether or not metformin is administered [35] and that no significant differences are observed after metformin treatment [36], [37]. In the current study, serum lactate levels in patients with and without metformin treatment did not differ significantly (n = 49 and 54, respectively, 1.11 ± 0.05 vs 1.04 ± 0.05 mmol/L). Some glucose-lowering therapies have been reported to be useful for fatty liver. It has suggested that the administration of pioglitazone let to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis [38]. In the current study, serum lactate levels in patients with and without thiazolidinedione treatment did not differ significantly (n = 7 and 96, respectively, 1.29 ± 0.26 vs 1.05 ± 0.03 mmol/L). It has also been shown that canagliflozin may improve liver function in T2DM with high alanine aminotransferase [39]. In the current study, serum lactate levels in patients with and without SGLT-2 inhibitor treatment did not differ significantly (n = 24 and 79, respectively, 1.13 ± 0.05 vs 1.05 ± 0.04 mmol/L). It has also been reported that liraglutide let to histological resolution of non-alcoholic steatohepatitis in T2DM [40]. In the current study, serum lactate levels in patients with and without GLP-1 receptor agonist treatment did not differ significantly (n = 6 and 97, respectively, 1.24 ± 0.17 vs 1.06 ± 0.03 mmol/L). However there were no difference in serum lactate levels depending on with or without any therapies which have been reported the utilities to fatty liver, further studies will be necessary because of the small number of patients. In addition, some previous studies already showed that higher γ-GTP levels were associated with onset of diabetes [41], [42], [43] and γ-GTP increased in patients with nonalcoholic steatohepatitis [44], [45]. However, there was no correlation between the serum lactate levels with the serum γ-GTP levels in the current study. It might be because the serum γ-GTP levels in the current study were lower than the levels which had been reported [41], [44], [45]. Alternatively, serum lactate may be an earlier indicator of fatty liver before γ-GTP increases.
PLGA –widely used polymeric excipient in medical applications Since its inception in 1970's Poly(lactic-co-glycolic acid) (PLGA), an aliphatic polyester, has always dominated the co-players due to its broad and unique physicochemical and biomedical applications. Several reviews discussed in detail the exceptional properties of PLGA and its wide use in medical applications, nanotechnology and tissue engineering [[1], [2], [3]]. Chemically PLGA is a random co-polymer of lactic acid (LA) and glycolic acid (GA). Upon degradation, it produces byproducts lactate and glycolate, which can enter the cell metabolic pathways, hence, the high biocompatibility and low toxic nature of PLGA. Feasibility to alter chemical properties of PLGA, such as monomer ratio of lactic acid and glycolic acid (LA:GA), and molecular weight, led to produce different grades of PLGA displaying different rate of hydrolysis. The degradation time can vary from several weeks to years. Hundreds of published articles and patents reported different types of PLGA or PLA based drug delivery systems (DDSs) such as nanoparticles, microparticles/spheres, implants, nanogels, nanofibers, rods, thin films, supporting matrices and combinations of these DDSs [1,3]. The loaded cargos in formulated PLGA delivery systems ranged from small molecules to large proteins, hydrophilic to lipophilic drugs, and single to multiple molecules [4]. PLGA-based DDSs can protect the drug cargo from degradation, sustain its release and modify its pharmacokinetics. Due to the commercial availability of GMP PLGAs (with LA:GA of 50:50, 65:35, 75:25, 85:15), versatility in degradation properties, sustained drug release and biodegradability and biocompatibility, PLGA is the most widely used polymer for drug delivery systems [1,3,5,6]. About two dozen PLGA-based drug delivery systems have been approved by regulatory agencies worldwide. The main challenges associated with PLGA DDSs, in particular PLGA-based nanoparticles, are low drug loading, unavailability of robust manufacturing techniques, stability issues of encapsulated drugs, initial burst, incomplete release, and regulatory issues [3,7]. However, different alternatives and mitigations have been developed to counter these potential drawbacks.