Literature data on compounds both well- and poorly-absorbed in humans were used to build a statistical pattern recognition model of passive intestinal absorption. Robust outlier detection was utilized to analyze the well-absorbed compounds, some of which were intermingled with the poorly-absorbed compounds in the model space. Outliers were identified as being actively transported. The descriptors chosen for inclusion in the model were PSA and AlogP98, based on consideration of the physical processes involved in membrane permeability and the interrelationships and redundancies between available descriptors. These descriptors are quite straightforward for a medicinal chemist to interpret, enhancing the utility of the model. Molecular weight, while often used in passive absorption models, was shown to be superfluous, as it is already a component of both PSA and AlogP98. Extensive validation of the model on hundreds of known orally delivered drugs, “drug-like” molecules, and Pharmacopeia, Inc. compounds, whic...

Prediction of drug absorption using multivariate statistics.

Significant opportunities and challenges exist in the creation and characterization of biomaterials. Materials have been designed for contact with blood, as replacements for soft and hard tissues, as adhesives, and as dental materials. Current methods of synthesis and characterization of these materials are outlined. Approaches for controlling the interface between tissue and biomaterials and ways in which the engineered materials may contribute to medicine are considered.

https://science.sciencemag.org/content/sci/263/5154/1715.full.pdf

New challenges in biomaterials

In situ degradation of metal-alloy implants is undesirable for two reasons: the degradation process may decrease the structural integrity of the implant, and the release of degradation products may elicit an adverse biological reaction in the host Degradation may result from electrochemical dissolution phenomena, wear, or a synergistic combination of the two Electrochemical processes may include generalized corrosion, uniformly affecting the entire surface of the implant, and localized corrosion, affecting either regions of the device that are shielded from the tissue fluids (crevice corrosion) or seemingly random sites on the surface (pitting corrosion) Electrochemical and mechanical processes (for example, stress corrosion cracking, corrosion fatigue, and fretting corrosion) may interact, causing premature structural failure and accelerated release of metal particles and ions

The clinical importance of degradation of metal implants is evidenced by particulate corrosion and wear products in tissue surrounding the implant, which may ultimately result in a cascade of events leading to periprosthetic bone loss Furthermore, many authors have reported increased concentrations of local and systemic trace metal in association with metal implants1,4,5,9-11,14,18,25,26,28,29,47,49-55,58,71,72,75-77,87,90,108-110 There also is a low but finite prevalence of corrosion-related fracture of the implant

This review focuses on electrochemical corrosion phenomena in alloys used for orthopaedic implants A summary of basic electrochemistry is followed by a discussion of retrieval studies of the response of the implant to the host environment and the response of local tissue to implant corrosion products The systemic implications of the release of metal particles also are presented Finally, future directions in biomaterials research and development …

/pdf/corrosion-of-metal-orthopaedic-implants-2h3sv09cdv.pdf

Corrosion of metal orthopaedic implants.

Application of chitosan and its derivatives as adsorbents for dye removal from water and wastewater: a review.

Transport phenomena through polymeric systems

Teratogenicity of Phthalate Esters in Rats

Toxicological evaluation of biomaterials: primary acute toxicity screening program.

Mutagenic and Antifertility Sensitivities of Mice to Di-2-ethylhexyl Phthalate (DEHP) and Dimethoxyethyl Phthalate (DMEP)

Monomers of five methacrylate esters and acrylic acid were administered at three dose levels to female rats on days 5, 10, and 15 of gestation. The incidences of resorptions, dead fetuses, gross abnormalities, and skeletal malformations are presented for each of these groups. Mean fetal weights also were determined for each group, and those of the monomer-treated groups were significantly smaller (P ≤ 0.01) than those of the untreated controls.

Embryonic-Fetal Toxicity and Teratogenic Effects of a Group of Methacrylate Esters in Rats

A group of 12 materials was evaluated for tissue compatibility via a sequential histopathologic evaluation of the rabit muscle response to the implanted materials. Tissue samples were obtained daily for 7 days and weekly for 12 weeks to follow the time course of the response. Some cytotoxic samples revealed a rapid and marked response of relatively short duration, whereas others tended to produce a sustained or a long-term, intermittent inflammatory and/or necrotic response. These effects also demonstrated the suitability of 7 days as a satisfactory time period for routine evaluation of rabbit muscle reaction to implanted materials. The histopathologic evaluation of the response was compared with a gross evaluation of the implant site and an independent test of the material by tissue culture (agar–overlay method).

John Autian

Papers

Teratogenicity of Phthalate Esters in Rats

Toxicological evaluation of biomaterials: primary acute toxicity screening program.

Mutagenic and Antifertility Sensitivities of Mice to Di-2-ethylhexyl Phthalate (DEHP) and Dimethoxyethyl Phthalate (DMEP)

Embryonic-Fetal Toxicity and Teratogenic Effects of a Group of Methacrylate Esters in Rats

Subacute toxicity testing of biomaterials using histopathologic evaluation of rabbit muscle tissue.