https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

23 Stereocontrol of Lactide ROP 6164 231 Isotactic Polylactides 6164 232 Syndiotactic Polylactides 6166 233 Heterotactic Polylactides 6166 3 Anionic Polymerization 6166 4 Nucleophilic Polymerization 6168 41 Mechanistic Considerations 6168 42 Catalysts 6169 421 Enzymes 6169 422 Organocatalysts 6169 43 Stereocontrol of Lactide ROP 6170 44 Depolymerization 6170 5 Cationic Polymerization 6170 6 Conclusion and Perspectives 6171 7 Acknowledgments 6173 8 References and Notes 6173

Controlled ring-opening polymerization of lactide and glycolide.

Polycaprolactone (PCL) is an important polymer due to its mechanical properties, miscibility with a large range of other polymers and biodegradability. Two main pathways to produce polycaprolactone have been described in the literature: the polycondensation of a hydroxycarboxylic acid: 6-hydroxyhexanoic acid, and the ring-opening polymerisation (ROP) of a lactone: e-caprolactone (e-CL). This critical review summarises the different conditions which have been described to synthesise PCL, and gives a broad overview of the different catalytic systems that were used (enzymatic, organic and metal catalyst systems). A surprising variety of catalytic systems have been studied, touching on virtually every section of the periodic table. A detailed list of reaction conditions and catalysts/initiators is given and reaction mechanisms are presented where known. Emphasis is put on the ROP pathway due to its prevalence in the literature and the superior polymer that is obtained. In addition, ineffective systems that have been tried to catalyse the production of PCL are included in the electronic supplementary information for completeness (141 references).

/pdf/synthesis-of-polycaprolactone-a-review-vlm9rxg878.pdf

Synthesis of polycaprolactone: a review

Injectable hydrogels with biodegradability have in situ formability which in vitro/in vivo allows an effective and homogeneous encapsulation of drugs/cells, and convenient in vivo surgical operation in a minimally invasive way, causing smaller scar size and less pain for patients. Therefore, they have found a variety of biomedical applications, such as drug delivery, cell encapsulation, and tissue engineering. This critical review systematically summarizes the recent progresses on biodegradable and injectable hydrogels fabricated from natural polymers (chitosan, hyaluronic acid, alginates, gelatin, heparin, chondroitin sulfate, etc.) and biodegradable synthetic polymers (polypeptides, polyesters, polyphosphazenes, etc.). The review includes the novel naturally based hydrogels with high potential for biomedical applications developed in the past five years which integrate the excellent biocompatibility of natural polymers/synthetic polypeptides with structural controllability via chemical modification. The gelation and biodegradation which are two key factors to affect the cell fate or drug delivery are highlighted. A brief outlook on the future of injectable and biodegradable hydrogels is also presented (326 references).

Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications

Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent.

Therapeutic inhibitor of vascular smooth muscle cells

A novel and efficient calcium alkoxide initiating system, generated in situ from bis(tetrahydrofuran)calcium bis[bis(trimethylsilyl)amide] and an alcohol, for the ring-opening polymerization of cyclic esters has been developed. The solution polymerization in THF using mild conditions is living, yielding polyesters of controlled molecular weight and tailored macromolecular architecture. The polymerizations initiated with the 2-propanol−Ca[N(SiMe3)2]2(THF)2 system are first-order in monomer with no induction period. At high 2-propanol/Ca[N(SiMe3)2]2(THF)2 ratios, complete conversion of 2-propanol occurs due to fast and reversible transfer between dormant and active species.

A novel and versatile calcium-based initiator system for the ring-opening polymerization of cyclic esters

An article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances, which wall is made using a biodegradable polymeric material permeable to the active substance, wherein the wall is composed mainly of a combination of at least two different polymeric materials in which one polymeric material is permeable to the active substance and is degradable and the other polymeric material is relatively poorly permeable to the active substance and is degradable and the conveyor path for the delivery of the active substance from the hollow space to the surroundings of the article is a continuous distance leading at least through the polymeric material permeable to the active substance.

Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances

In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8 and PEG-(PDLA)8 star block copolymers.

A series of aluminum ethyls and isopropoxides based on a bis(pyrrolidene) Schiff base ligand framework has been prepared and characterized. NMR studies of the dissolved complexes indicate that they adopt a symmetric structure with a monomeric, five-coordinated aluminum center core. The aluminum ethyls used as catalysts in the presence of 2-propanol as initiator and the aluminum isopropoxides were applied for lactide polymerization in toluene to test their activities and stereoselectivities. All polymerizations are living, as evidenced by the narrow polydispersities and the good fit between calculated and found number-average molecular weights of the isolated polymers. All of these aluminum complexes polymerized (S,S)-lactide to highly isotactic PLA without epimerization of the monomer, furnished isotactic-biased polymer from rac-lactide, and gave atactic polymer from meso-lactide. The study of kinetics indicated that the activity of the bis(pyrrolidene) Schiff base aluminum initiator systems toward lactid...

Polymerization of Lactide Using Achiral Bis(pyrrolidene) Schiff Base Aluminum Complexes

The isothermal crystallization behavior of low-molecular-weight (DP 50) poly(l-lactide-b-d-lactide) diblock copolymers is reported, as studied by small- and wide-angle X-ray scattering. The symmetric diblock copolymer crystallizes in the stereocomplex form for the whole range of crystallization temperatures, while the one with a block ratio of 80/20 grows into homocrystallites. For an intermediate block ratio (66/33), the stereocomplex form is obtained at high crystallization temperatures while a coexistence region with homocrystal phase exists at low temperatures. In addition to the transition enthalpy, size effects and kinetic routes play a role in the competition between the stereocomplex and the homocrystalline forms. The lamellar spacing (long period and crystal thickness) shows a different temperature dependence for the three diblock copolymers, which is discussed in relation to the specific morphology and molecular constitution.

http://wimdejeu.nl/onewebmedia/all%20publications/125%20Macrom%202004%20Li-lactide.pdf

Jan Feijen

Papers

A novel and versatile calcium-based initiator system for the ring-opening polymerization of cyclic esters

Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances

In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8 and PEG-(PDLA)8 star block copolymers.

Polymerization of Lactide Using Achiral Bis(pyrrolidene) Schiff Base Aluminum Complexes

Crystal Structure and Morphology of Poly(L-lactide-b-D-lactide) Diblock Copolymers