Mattheus F. A. Goosen

Applications and Properties of Chitosan

Chitosan, a polycationic polymer and waste product from the sea food processing industry, is an abundant natural resource that has, as yet, not been fully utilized. Advantages of this polymer include availability, low cost, high biocompatibility, biodegradability and ease of chemical modification. In this paper, the physicochemical properties of chitosan, as well as its numerous applications, are reviewed with particular emphasis on its use in water treat ment, pharmaceutics, agriculture and membrane formation.

Role of polymers in improving the results of stenting in coronary arteries

This article is a review of recent developments of polymer-related stents mainly employed in the coronary arteries, including polymer-coated stents, biostable stents and biodegradable stents. Polymer paving is covered as well. The problems with the stents currently investigated and the development of new stents are discussed.

Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane

Prolonged survival of islet allografts in streptozotocin-induced diabetic rats was achieved by encapsulating individual islets in protective, biocompatible alginate-polylysine-alginate membranes. A single intraperitoneal transplant of encapsulated islets reversed the diabetic state for up to 1 year. In contrast, a single injection of unencapsulated islets was effective for less than 2 weeks. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential in the treatment of diseases requiring organ transplantation, such as diabetes and liver disease.

Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

Abstract— Controlled antibiotic release films, melt‐extruded cylinders, and suspension‐extruded/coated cylinders were manufactured from biodegradable poly(d, l‐lactide) (PDLLA) and poly(d, l‐lactide‐co‐∈‐caprolactone). These devices have potential application in the treatment of osteomyelitis. The in‐vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt‐extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt‐extruded cylinders made from poly(d, l‐lactide‐co‐∈‐caprolactone), low mol. wt poly(d, l‐lactide), and a mixture of d, l‐lactic acid oligomer and high mol. wt poly(d, l‐lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110°C. Antibiotic release from high mol. wt PDLLA‐coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA‐coated cylinders 0·2, 0·4, 0·7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients. Cephazolin and benzylpenicillin were found to be unsuitable for sustained release longer than 300 h due to the hydrolytic instability of the drugs in water.

An Investigation of Poly(lactic acid) Degradation

To elucidate the degradation mechanism of poly(lactic acid), the decrease in the intrinsic viscosity of poly(D,L-lactide) in a homogeneous water/ acetone solution was investigated. The hydrolysis of poly(D,L-lactic acid) in water/acetone solution can be catalyzed by protons. The molecular weight degradation of solid poly(D,L-lactic acid) in water was primarily affected by the degree of polymer purity. Polymerization conditions such as initiator concen tration, temperature and time did not have an obvious effect on the molecular weight degradation. In the case of polymer samples with low purity (i.e., directly polymerized or containing solvent or oligomer), degradation was ini tially very rapid. On the other hand, initial degradation of purified polymer was very slow before accelerating.

Microcapsules/Microspheres Related to Chitosan

Abstract Chitosan [(1-4) 2-amino 2-deoxy-β-D-glucan] is a polyaminosacchar-ide, normally obtained by alkaline deacetylation of chitin which is a very abundant naturally occurring polymeric material. It occurs as a principle constituent of the protective cuticles of crustacea and insects and also in the cell walls of some fungi and microorganisms.

An examination of factors affecting the size, distribution and release characteristics of polymer microbeads made using electrostatics

A new technique of generating polymeric monolithic microbeads containing solid protein particles has been developed. The method involves extruding a suspension of protein particles within a polymer solution through a needle and into an electric field. The electric field force effectively pulls the forming droplet off the end of the needle, producing a series of smaller droplets. A factorial design investigation of the extrusion process using bovine serum albumin particles suspended in ethylene vinyl acetate dissolved in dichloromethane, illustrated that the size of the microbead was controlled primarily by the strength of the electric field and the gauge of the needle used. Smaller microbeads were formed by increasing the applied electric field and using a higher gauge (smaller internal diameter) needle. However, the reduction in microbead average diameter came at the expense of a much broader distribution of microbead diameters. Release studies using the microbeads illustrated the ability of the process to encapsulate and slowly release protein. From these studies, the critical volumetric loading of the microbeads was determined and found to be dependent on the size of the incorporated protein particles.

An investigation of the synthesis and thermal stability of poly(dl-lactide)

SummaryThe synthesis and thermal degradability of poly (DL-lactide) were investigated. Key factors affecting the polymer molecular weight were found to be monomer recrystallization, initiator concentration and the vacuum level during drying/sealing of the polymerization reaction ampoule. It was found that poly (DL-lactide) is thermally unstable above its melting temperature. Monomer recrystallization, polymer precipitation and a low initiator content of the polymer significantly inhibited the rate and extent of thermal degradation.

In vitro and in vivo release of insulin from poly(lactic acid) microbeads and pellets

Abstract A feasibility study was carried out on developing an alternative insulin delivery system, for the treatment of insulin-requiring adult-onset (Type II) diabetes, which would by-pass some of the unresolved problems associated with mechanical insulin pumps. In our system, insulin delivery was accomplished by the sustained release of the hormone from a biodegradable polymer matrix, poly(1-lactic acid) (PLA). Injectable insulin—PLA microbeads and implantable pellets were prepared using an emulsion/solvent evaporation technique and a solvent casting technique respectively. Insulin—PLA microbeads retained between one-tenth and three-quarters of the loaded insulin. S.E.M. analysis of the microbeads revealed surface insulin crystals and distinct channels in the PLA matrix. It was found that the 1% to 2% poly(vinyl alcohol) emulsifier assisted in the formation of these surface insulin crystals. In vitroabout 50% of the insulin eluted from the microbeads into tris buffer within the first hour. The duration of action of the microbeads could be varied from a few hours to several days. Compared with the microbeads, insulin—PLA pellets showed a relatively small in vitro insulin burst effect and an almost constant insulin release rate during the first 13 hours (7.3 U/h). A pore-release model was used to describe the mechanism of insulin release from the polymer matrix. In animal studies, insulin—PLA preparations, administered subcutaneously as a single injection of microbeads or by implantation of a pellet, lowered the blood glucose levels of chemically induced diabetic rats for more than two weeks.

Synthesis of Chitosan-Alginate Microcapsule Membranes

A polysaccharide, chitosan, was chemically modified to form a polyelectrolyte complex membrane with calcium alginate beads. A key factor in membrane for mation was found to be the viscosity average molecular weight (M v) of the chitosan. While unmodified chitosan (Mv = 12.1 x 105) formed thin and weak microcapsule membranes, when the Mv of the chitosan was reduced to 2.4 x 105, the polymer exhibited optimum membrane forming characteristics in terms of capsule strength and flexibility. The degree of deacetylation of chi tosan varied from 94.3% for the unmodified polymer to 93.2% for chitosan of Mv = 1.6 × 105. A substitution reaction sequence was developed in an attempt to modify the pendant amine of the practical grade polysaccharide. Reactive groups were coupled to the chitosan main chain following a two-step process; activation with a bromoacetyl halide and termination with a diamine [(NH2 (CH2)nNH2)] or methyl containing amine compound. Initial studies indicated that thin capsule membranes formed regardless of application of reaction se quence, distance of reactive groups from the main chain, or type of reactive group inserted. The permeability of the chitosan-alginate capsules was assessed, with various diffusing proteins. Membranes formed with chitosan Mv =0.5 × 106 excluded beta amylase, suggesting a membrane molecular weight cut-off of approximately 200,000.