ABSTRACT
The technology of lipid-drug conjugates is developed on the basis of prodrug principle, which overcomes some drawbacks of drugs via increasing the lipophilicity of hydrophilic or poorly soluble drugs to promote the absorption of drugs and enhance the curative effect. This article sums up the research progress of lipid-drug conjugates from the chemical synthesis methods of conjugates, the types of conjugates, the influence on biological activity of drugs, the application in nanoparticles for drug delivery and the mechanism of absorption and degradation.
ABSTRACT
BACKGROUND:Studies have shown that bioactive molecules or polypeptides grafted onto the surface of polyethylene glycol (PEG) hydrogels can improve PEG bioactivities.OBJECTIVE:To manufacture PEG hydrogels capable of auto-recruiting growth factor beta1 (TGF-β1) and to study its biocompatibility. METHODS:Pure PEG hydrogels (group A), PEG hydrogels grafted on a cell adhesion peptide RGD peptides (group B), PEG hydrogels grafted with auto-recruited TGF-β1 peptide sensitive polypeptide HSNGLPL (group C), PEG hydrogels grafted with both RGD and HSNGLPL polypeptides (group D) were prepared. Contract angle of the hydrogel was detected in each group. Human bone mesenchymal stem cells were seeded onto four kinds of hydrogels. After cells attached, scanning electron microscope and LIVE/DEAD staining were done to observe cell-hydrogel compounds. Human bone marrow mesenchymal stem cells were co-cultured with ordinary culture medium (control) or four kinds of hydrogels for 1, 3, 5, 7 days, and the cell proliferation was detected by cell counting kit-8 assay. The four kinds of hydrogels were put into 24-well culture plates with addition of PBS containing TGF-β1, and 1 hour later, immunofluorescence staining was done. RESULTS AND CONCLUSION:(1) The contact angles of groups A and C were larger than those of groups B and D. (2) Under the scanning electron microscope, groups A and C had little cells attached on the hydrogel surface, but there were many cells on the hydrogel surface in groups B and D. (3) LIVE/DEAD staining showed groups A and C had little living cells, and conversely groups B and D had many living cells. (4) The results of cell counting kit-8 demonstrated that as the incubation time went on, cell proliferation activity of five different groups increased with no difference at the same time point. (5) Findings from the immunofluorescence staining showed that groups A and B had very weak fluorescence, while groups C and D had stronger green fluorescence. In conclusion, PEG hydrogels grafted with RGD and HSNGLPL polypeptides can auto-recruit TGF-β1, and have good biocompatibility.
ABSTRACT
BmNPV GD isolate from China was plaque-purified and four bro genes were cloned termed as bro-a,b,c,d. The obtained sequences were aligned to the related sequences in GenBank and the BmNPV CQ1 isolate preserved in our laboratory. Compared with genome sequences of BmNPV T3 isolate, bro genes of GD isolate housed insertion and deletion, and the changes of amino acid mainly occured at the N terminal of corresponding protein. The phylogenetic analysis of bro genes indicated that GD bro-d gene belongs to subgroup A together with T3, CQ1 bro-d and SC7 bro- III; GD bro-a, c genes belong to subgroup B together with T3, CQ1 bro-a, c and SC7 bro-II; GD bro-b gene belongs to subgroup C together with T3, CQ1 bro-b, e and SC7 bro-I. The evolutionary relationship of bro genes showed vague relevance to their geographical location. The distribution character of bro genes in four BmNPV isolates is coincidence with the KANG's theory that the bro-d plays an irreplaceable functional role(s) during viral replication, while bro-a and bro-c functionally complement each other. Meanwhile, we postulate that 3 bro genes in SC7 isolate is probable the most simple form of bro genes.