Stephen Brocchini

Narrow Molecular Weight Distribution Precursors for Polymer–Drug Conjugates

Atom transfer polymerization has been used to prepare a narrow molecular weight distribution (MWD), active ester homopolymer that acted as a precursor to prepare families of narrow MWD polymer-drug conjugates during preclinical studies.

Modulation of wound healing during and after glaucoma surgery.

Following all types of glaucoma filtration surgery (GFS), scarring still poses the major threat to long-term success. The healing and scarring determine the percentage of patients achieving low final intraocular pressures (IOPs) that are associated with virtually no glaucoma progression. The use of antifibrotic agents to inhibit scarring of trabeculectomy blebs is now a well-established clinical practice. Unfortunately, severe complications such as leakage, infection, hypotony, and endophthalmitis with complete loss of vision may occur. In addition, surgery still fails in some individuals despite maximal doses of current antifibrotics. Better therapeutic agents are needed. Many promising new agents are being evaluated clinically and in vitro. In this chapter, we will discuss our current understanding of the wound healing process after glaucoma surgery and promising new treatment modalities.

Synthesis of soluble polymers for medicine that degrade by intramolecular acid catalysis

Aqueous soluble polymers designed to rapidly degrade by an intramolecular assisted acid catalysed mechanism were prepared. Degradation studies at pH 5.5 and 2.0 exhibited a rapid first phase followed by a slower phase and incomplete degradation to macromonomeric species. The fast phase was attributed to repeat units containing a carboxylic acid pendent chain cis to an amide bond in the polymer mainchain and the slow phase by the absence of this free carboxylic acid moiety.

The Molecular Interactions That Influence the Plasticizer Dependent Dissolution of Acrylic Polymer Films

Poly(methacrylic acid-methyl methacrylate, 1:2) (Eudragit S) is a commonly used pH-responsive polymer that can facilitate delivery to the ileo-colonic region of the gastrointestinal tract. Different plasticizers have been used to reduce the brittleness of Eudragit S films for the coating of solid dosage forms. To better correlate the dissolution rates of Eudragit S films, we have examined their dielectric response to understand the specific polymer-plasticizer interactions. Solvent cast Eudragit S films were prepared with one of four citrate plasticizers ranging from low to moderate aqueous solubility. Film dissolution was determined using a two-compartment permeation cell. Dielectric properties were measured by thermally stimulated depolarisation currents (TSDC). Secondary relaxations were deconvoluted and identified. The glass transition temperature (T(g)) was measured using TSDC, differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). Dissolution of the films was influenced by the solubility and structure of the plasticizers. While no correlation was found among the T(g)s obtained by TSDC, DSC, and DMA with dissolution time, the low temperature TSDC spectra showed a relationship of the total secondary relaxation area and relaxation of the carboxylic acid functional group with dissolution time. Dielectric secondary relaxations may be a good probe to predict plasticizer influence on dissolution of Eudragit S polymer films.

The use of precursor polymers to prepare new excipients

Polymers are ubiquitous excipients in medicines and are widely used in drug delivery systems. To address the need for novel polymers that can enhance the properties of formulations, narrow molecular weight distribution precursor polymers are used to prepare candidate polymers for a range of pharmaceutical applications. Both a homopolymer and block copolymer precursor were utilised in this study to give functional polymers. Thiomers were prepared from the homopolymer precursor and latently hydrophilic block copolymers were prepared from the copolymer precursor.

Tissue Repair and Regeneration

Publisher Summary Damage and degeneration of tissues in and around the eye frequently leads to visual impairment because of the anatomy and physiology of the eye. Consequently, repair processes play a role in most major blinding eye conditions or the failure of treatment. Cataract is the most important cause of world blindness, and degenerative processes with a repair response play a part in both the formation of cataract and the after cataract in capsule sparing surgery. Lid contraction and corneal scarring result in blindness in trachoma, and conjunctival fibrosis blinds after burns or autoimmune diseases such as cicatricial pemphigoid. Following glaucoma surgery, post-operative sub-conjunctival scarring results in sub-optimal pressure control and disease progression, and similar scarring restricts the predictability of strabismus surgery and contributes to motility problems in thyroid eye disease. Retinal scarring in proliferative vitreoretinopathy, and specifically age related macular degeneration, results in more loss of vision than any other disease in the developed world. Treatments and surgical approaches have been developed to successfully modulate the wound healing response. Anti-cancer agents such as mitomycin C inhibit fibroblast function and survival when applied locally. Steroids applied topically and systemically reduce inflammation and fibrosis. However, both these agents have significant side effects. This chapter reviews the agents used to modulate healing scarring.