Subcutaneous implants

Classification of the anabolic steroids is based on chemical stmctures and associated actions. A review of the biosynthesis and metabolism of the naturally occurring estrogens and androgens is available (1). Names, descriptions, approval dates, and recommended doses of the commercial products are found in References 1, 8, and 9. Although steroids may be orally active, the FDA approved mode of adrninistration is the subcutaneous implant. Effective dose is lower with implant rather than oral adrninistration. 

The rate of in vivo biodegradation of subcutaneous implanted films was very high for chitin compared with that for deacetylated chitin. No tissue reaction was foimd with highly deacetylated chitosans, although they contained abundant primary amino groups [240]. 

In vivo biocompatibility was assessed through subcutaneous implantation in Sprague-Dawley rats. PLGA was used as a control polymer. PGS and PLGA implants with the same surface area/volume ratio were implanted in dorsal subcutaneous pockets. A fibrous capsule around PGS (45 pm thick after 35 days implantation) appeared later than that around PLGA (140 pm thick after 14 days implantation). After 60 days of implantation, the implant was completely absorbed with no signs of granulation or scar formation. ... 

Naltrexone in combination with lactide/glycolide copolymer has been investigated (83-87). Chiang (85) reported the clinical evaluations of a bead preparation containing 70% naltrexone and 30% of a 90 10 lactide/glycolide copolymer. Each subject received a 10-mg i.v. dose of naltrexone and a 63-mg dose by subcutaneous implantation of the beads. Average plasma naltrexone levels were maintained at 0.3-0.4 ng/ml for approximately 1 month. Two out of three subjects experienced a local inflammatory reaction at the site of implantation. This unexplained problem prevented further clinical testing of... 

The development of a bioerodible implant capable of releasing controlled amounts of a contraceptive steriod from a subcutaneous implant for periods of time ranging from three months to about a year has been in progress for many years. The three principal bioerodible polymers currently in use are copolymers of lactic and glycolic acid (25), poly(e-caprolactone) (26), and poly (ortho esters) (14). The desire to develop such a contraceptive system was the principal motivation for the initial development of the poly(ortho ester) polymer system. 

Next, a 1 year subcutaneous implantation study in mice was performed (22). Small pieces of poly(N-palmitoylhydroxyproline ester) (approximately 10 mg per implant) were implanted subcutaneously in the dorsal area of the animals. The implants were placed between the dermis and the adipose tissue layer. Groups of mice were sacrificed 4, 7, 14, 16, and 56 weeks postimplantation. 

Although the initially reported tissue compatibility tests for subcutaneous implants of poly(BPA-iminocarbonate) were encouraging (41,42), it is doubtful whether this polymer will pass more stringent biocompatibility tests. In correspondence with the properties of most synthetic phenols, BPA is a known irritant and most recent results indicate that BPA is cytotoxic toward chick embryo fibroblasts in vitro (43). Thus, initial results indicate that poly(BPA-iminocarbonate) is a polymer with highly promising material properties, whose ultimate applicability as a biomaterial is questionable due to the possible toxicity of its monomeric building blocks. 

In order to test the tissue compatibility of tyrosine-derived poly-(iminocarbonates), solvent cast films of poIy(CTTH) were subcutaneously implanted into the back of outbread mice. In this study, conventional poly(L-tyrosine) served as a control (42). With only small variations, the experimental protocol described for the biocompatibility testing of poly(N-palmitoylhydroxyproline ester) (Sec. III. 

Recently, it was found that single-housed mice that had been undergoing withdrawal for 48 hours (after removal of a subcutaneously implanted 75-mg morphine pellet) showed an elevation of attack and threat behavior that was doubled when these mice were challenged with amphetamine, cocaine, /-dopa, or apomorphine (figure 4) (Kantak and Miczek 1986 ... 

Only a few in vivo dermal toxicity studies have been reported so far. Huczko and Lange [50] evaluated the potential of raw CNTs to induce skin irritation by conducting two routine dermatological tests (patch test on 40 volunteers with allergy susceptibilities and Draize rabbit eye test on four albino rabbits). Koyama etal. [51] showed the biological responses to four different types of carbon nanotubes (SWNTs, two types of MWNTs with different diameters, and cup-stacked carbon nanotubes) after their subcutaneous implantation in mice. Both tests [50, 51] showed no or poor irritation effects. However, the in vitro studies in epidermal cell lines exposed to CNTs, and also a more recent report on the toxic outcomes of topical exposure of mice to SWNTs [46], have raised concerns over these assessments. Clearly, this is an area requiring further scientific evaluation. 

Koyama, S. et al. (2006) Role of systemic T-cells and histopathological aspects after subcutaneous implantation of various carbon nanotubes in mice. Carbon, 44 (6), 1079-1092. 

Most of the recent attention has been given to the development of subcutaneously implantable needle-type electrodes [14, 15, 34, 38], Such devices track blood glucose levels by measuring the glucose concentration in the interstitial fluid of the subcutaneous tissue (assuming the ratio of the blood/tissue levels is constant). Subcutaneously implantable devices are commonly designed to operate for a few days and be replaced by the patient. Success in this direction has reached the level of short-term human implantation ... 

E. Csoregi, D.W. Schmidtke, and A. Heller, Design and optimzation of a selective subcutaneously implantable gluocse electrode based on wired glucose oxidase. Anal. Chem. 67, 1240-1244 (1995). 

E Moussy and D.J. Harrison, Prevention of the rapid degradation of subcutaneously implanted Ag/AgCl reference electrodes using polymer coatings. Anal. Chem. 66, 674-679 (1994). 

Subcutaneous implant Testosterone (Testopel) 75-mg pellet 150-450 mg every 3-4 months... 

Kupchan and Doskotsch (9) found that an alcoholic extract of A. indica possessed reproducible activity against the adenocarcinoma 755 test system. The active principle, aristolochic acid I, was isolated and characterized. Kamatsh and co-workers (97) reported that growth of mouse sarcoma-37 cells incubated with aristolochic acid at concentration of 100-200 p-g/ml for 3 hr was completely inhibited. Treatment of mice with aristolochic acid (1.25-5 mg/kg ip per day) for 3 days after subcutaneous implantation of sarcoma-37 cells inhibited tumor growth in 40-50%. A dose of 2.5-5 mg/kg ip per day for 5 days remarkably prolonged survival. The cytotoxic effect on HeLa cells in culture was observed at a concentration of 25 p-g/ml. 

Estrogens are administered orally, parenterally by injection or as subcutaneous implants, transdermally and topically. After oral administration a considerable first pass effect, both in the intestinal mucosa and in the liver, takes place with large interindividual variability. Estrogens are hydroxylated and conjugated in the liver and excreted mainly in the bile. The conjugates can be hydrolyzed in the intestine to active compounds that are reabsorbed again. Their hepatic oxidative metabolism is increased by enzyme inducers and the enterohepatic circulation may be decreased by some antibiotics which disturb the intestinal bacterial flora. 

Capsules for subcutaneous implantation, containing levonorgestrel for contraception and levonorgestrel containing intra-uterine devices are available in some countries. They are highly effective and their efficacy lasts for several years. 

J. R. James, Y. Gao, V. C. Soon, S. M. Topper, A. Babsky and N. Bansal, Controlled radiofrequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by H, Na and P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma. Int.. Hyperthermia, 2010, 26, 79-90. 

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