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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of a single-dose tetanus vaccine based on Poly(Lactic acid) (PLA) or Poly(Lactide-co-Glycolide) (PLGA) microspheres has been complicated due to the instability of tetanus toxoid (TT) inside these systems. Herein we report an attempt to re-design PLGA microspheres by co-encapsulating TT in the dry solid state together with potential protein stabilizers, such as trehalose, bovine serum albumin, alginate, heparin, dextran or poloxamer 188 and by using an appropriate microencapsulation technique. These newly developed PLGA microspheres were able to release in vitro antigenically active TT for at least 5 weeks, the amount released being highly dependent on the stabilizing excipient used. More specifically, results showed that dextran and heparin provided a particularly stabilizing environment for TT inside the microspheres during the polymer degradation process. The efficacy of this strategy was demonstrated by the high, long lasting titers of neutralizing antibodies achieved after in vivo administration of dextran-containing microspheres with a small amount of alum-adsorbed TT, as compared to the commercial adsorbable tetanus vaccine. These findings suggest that future developments in the area of vaccinology depend on ability to combine a detailed knowledge of the microencapsulation technology with a rational choice of stabilizing excipient or combination of excipients.
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PMID:Formulation strategies for the stabilization of tetanus toxoid in poly(lactide-co-glycolide) microspheres. 1046 Sep 20

From reactions between glycolide or lactide (4 equiv.) with 4-dimethylaminopyridine, DMAP (1 equiv.) and NaBPh(4) (1 equiv.) in benzene at 70 degrees C the cyclic ester adducts (CH(2)C(O)O)(6)NaBPh(4) and (CHMeC(O)O)(6)NaBPh(4) are formed respectively. The structures of the salts Na[(S,R,S,R,S,R)-(CH(3)CHC(O)O)(6)](2)BPh(4).CH(3)CN and (CH(2)C(O)O)(6)NaBPh(4).(CH(3)CN)(2) are reported. The cyclic esters were separated by chromatography and the structures of (CH(2)C(O)O)(6), (S,R,R,R,R,R)-(CHMeC(O)O)(6) and (S,S,R,R,R,R)-(CHMeC(O)O)(6) were determined. The (1)H and (13)C NMR data are reported for one of each of the six enantiomers of (CHMeC(O)O)(6) and the two meso isomers. The mechanism for the formation of these 18-membered rings is discussed in terms of an initial reaction between DMAP and NaBPh(4) in hot benzene that produces NaPh and DMAP:BPh(3) in the presence of the monomer lactide. The cyclic esters (CHMeC(O)O)(6) can also be obtained from the reaction between polylactide, PLA, in the presence of DMAP and NaBPh(4). The cyclic esters 3-methyl-1,4-dioxane-2,5-dione and 3,6,6-trimethyl-1,4-dioxane-2,5-dione undergo similar ring enlarging reactions to give cyclic 18-membered ring esters as determined by ESI-MS.
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PMID:18-membered cyclic esters derived from glycolide and lactide: preparations, structures and coordination to sodium ions. 1795 33

(6S)-3-Methylene-6-methyl-1,4-dioxane-2,5-dione was synthesized from L-lactide and used as the dienophile to prepare spiro[6-methyl-1,4-dioxane-2,5-dione-3,2'-bicyclo[2.2.1]hept[5]ene] via an exoselective and diastereofacial-selective Diels-Alder reaction. Polymerizations of this bifunctional lactide derivative were successfully carried out under ring-opening and ring-opening metathesis polymerization conditions to yield high molecular weight and high Tg polymers. We further demonstrated that by incorporating a small percentage of spiro[6-methyl-1,4-dioxane-2,5-dione-3,2'-bicyclo[2.2.1]hept[5]ene] into poly(1,5-cyclooctadiene) and copolymerizing it with DL-lactide, novel polymeric alloys of PLA can be created that have tremendous improvements in toughness over PLA and the corresponding binary blend of PLA and poly(1,5-cyclooctadiene).
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PMID:A bifunctional monomer derived from lactide for toughening polylactide. 1882 59

Biodegradable and bioabsorbable poly(lactic acid)s are one of the most important biomedical materials. However, it is difficult to introduce the functional groups into poly(lactic acid)s in order to improve their hydrophilicity and degradation rate. Here the authors describe the synthesis of functionalized cyclic lactide monomer 3,6-bis(benzyloxymethyl)-1,4-dioxane-2,5-dione (BnLA) using an advanced synthetic route. Water-soluble hydroxyl-functionalized homopoly(lactic acid) (P(OH)LA) is synthesized via ring-opening polymerization (ROP) of BnLA, followed by a hydrogenolytic deprotection reaction. Amphiphilic diblock poly(lactic acid) (P(OH)LA-PLA) is synthesized via ROP of DL-lactide using PBnLA as an initiator, followed by a hydrogenolytic deprotection reaction. P(OH)LA-PLA is able to form polymeric micelles with the diameter of sub-100 nm.
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PMID:A Functionalized Cyclic Lactide Monomer for Synthesis of Water-Soluble Poly(Lactic Acid) and Amphiphilic Diblock Poly(Lactic Acid). 2785 72