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Hairy root cultures of Trigonella foenum-graecum L. were established with Agrobacterium rhizogenes strain A 4 . The hairy roots produce diosgenin, an important spirostanol for the semi-synthesis of steroid hormones. Fourteen different liquid media were investigated. The fastest growth was obtained in McCown's woody plant (WP) medium supplemented with 3% sucrose; the highest diosgenin content was observed in half-strength WP medium with 1% sucrose (0.040% dry weight), which represents almost twice the amount detected in the 8-month-old non-transformed roots (0.024%). A time-course study in WP liquid media supplemented with 3% sucrose was undertaken. In these conditions, 17 µg diosgenin/g fresh weight were produced. The influence of cholesterol, medium pH and chitosan on diosgenin production was tested. The addition of 40 mg/l chitosan elevated the diosgenin content to three times that found in non-elicited hairy roots.

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Since the late 1970s, three families of poly(ortho esters) (POE) were synthesized to provide bioerodible carriers for drug delivery devices. The most recent POE is a semi-solid polymer with a viscous behavior at room temperature. Polymer synthesis by a transesterification reaction between a triol and a trialkyl ortho ester is described. The structure of the polymer was confirmed by conventional methods such as 1H-NMR, 13C-NMR and FT-IR. Information concerning average molecular weight and intrinsic viscosity was obtained respectively by GPC and viscosimetry. Residual solvents in the polymer were determined using gas chromatography. The chromatographic conditions were optimized to enable the quantification of the solvents in concentrations of a few percent. The mechanical behavior of the semi-solid POE was determined by rheometric measurements. Hydrolysis of the polymer leads to the formation of the original triol and the carboxylic acid derived from the trialkyl ortho ester used in the transesterification step. No toxicological problems associated with these compounds are anticipated.

We evaluated the biotolerance of a new semisolid poly(ortho ester) (POE) intended for controlled drug delivery. Two different investigations were carried out in rats: subcutaneous injections and the cage-implant system. Sodium hyaluronate (SH), 1%, in phosphate buffer was used as a noninflammatory control. When injected subcutaneously in rats, the POE induced a mild and local inflammation at 3 and 7 days followed by a minimal chronic inflammation at 14 and 21 days. When using the cage-implant system, we quantified the inflammatory components of the exudate surrounding the implanted material within the cage system at 3, 7, 14, and 21 days. The total leukocyte and macrophage concentrations were higher only at 7 days for both SH and POE compared to the control (empty cage). The other parameters were not significantly different from the control. These results show that POE is well-tolerated by rats when used subcutaneously.

The biocompatibility of a new semisolid, hydrophobic poly(ortho ester) (POE) intended for controlled drug delivery to the eye was evaluated. The polymer was injected subconjunctivally in rabbits, and clinical and histologic examinations were performed 3, 10, 15, and 21 days after injection. Polymers injected as controls were an aqueous gel of sodium hyaluronate (SH), 1% in phosphate buffer, and medical grade silicone oil. After injection, the POE emulsified into small droplets and a focal eosinophilic reaction was noted at 3 days' implantation. At 10 days' implantation, the POE was not identified in the implantation site and the inflammatory reaction had resolved, with fibroblasts being the predominant cell type. At 15 and 21 days, no POE was identified and normal appearing tissue was present in the injection site. Sodium hyaluronate was not inflammatory over the period of the implantations. Silicone oil induced a slight inflammation at 3 days, with the presence of eosinophils and limited necrosis with cellular debris. Silicone oil was present in the implantation site at 3, 10, 15, and 21 days. The inflammatory response to the respective polymers was evaluated in the subconjunctival tissue. The inflammatory reaction was quantified at the implant site, adjacent subconjunctival tissues, and scleral and corneal stroma. The inflammatory cell densities in these respective tissue zones were determined, and the ratio of eosinophils over total inflammatory cells was calculated. POE did not become encapsulated with fibrous tissue, but biodegraded in a short time, indicating its potential for use after glaucoma filtration surgery.