Biomedical subjects

J F McBride

Publications and source records attributed to J F McBride.

6 recordsLinked to original sources

PubMed1998

Enhanced loading and activity retention of bioactive proteins in hydrogel delivery systems.

A simple, general and effective technique is developed for increasing the loading of bioactive macromolecules into hydrogels using the principles of aqueous two-phase extraction. Model proteins, ovalbumin and alpha-amylase, were loaded into hydrated gels by soaking the gels in a buffered solution of protein containing 12 wt% PEG-10000 and 0.22 M salt (KCl, KBr or KI). The PEG and salts were expected to enhance protein sorption according to aqueous two-phase extraction heuristics. In the absence of the solution additives, the gels absorbed little protein. But protein loading up to 270 mg ovalbumin/g polymer and 67 mg alpha-amylase/g polymer was obtained when the PEG and salt were added; loading was not significantly dependent upon salt type. Ovalbumin release from hydrated gels was diffusion-controlled. The diffusion coefficient was 1.10 (-7) cm2/s, consistent with protein absorption into the gel rather than adsorption onto the surface. Release kinetics of both proteins from dried, glassy gels matched conventional behavior for release of absorbed drugs from glassy polymers. Finally, alpha-amylase activity was retained even after drying the loaded gel at 65 degreesC, conditions which denatured the enzyme when not absorbed in the gel.

Algorithms↗

PubMed1998

Protein sorption and recovery by hydrogels using principles of aqueous two-phase extraction.

Use of the thermodynamic principles of aqueous two-phase extraction (ATPE) to drive protein into a crosslinked gel is developed as a protein isolation and separation technique, and as a protein loading technique for drug delivery applications. A PEG/dextran gel system was chosen as a model system because PEG/dextran systems are widely used in aqueous two-phase extraction and dextran gels (Sephadex(R)) are common chromatographic media. The effects of polymer concentrations and molecular weights, salts, and pH on the partitioning of ovalbumin matched ATPE heuristics and data trends. Gel partition coefficients (Cgel/Csolution) increased with increasing PEG molecular weight and concentration and decreasing dextran concentration (increased gel swelling). The addition of PEG to the buffer solution yielded partition coefficients more than an order of magnitude greater than those obtained in systems with buffer alone, or added salt. A combined salt/PEG system yielded an additional order of magnitude increase. For example, when ovalbumin solution (2.3 mg/mL) was equilibrated with Sephadex(R) G-50 at pH 6.75, the partition coefficients were 0.13 in buffer, 0.11 in buffer with 0.22M KI, 2.3 in 12 wt% PEG-10,000 and 32.0 in 12 wt% PEG-10, 000 with 0.22M KI. The effect of anions and cations as well as ionic strength and pH on the partitioning of ovalbumin also matched ATPE heuristics. Using the heuristics established above, partition coefficients as high as 80 for bovine serum albumin and protein recoveries over 90% were achieved. In addition, the wide range of partition coefficients that were obtained for different proteins suggests the potential of the technique for separating proteins. Also, ovalbumin sorption capacities in dextran were as high as 450 mg/g dry polymer, and the sorption isotherms were linear over a broad protein concentration range.

Adsorption↗

PubMed1996

Synergistic topical photoprotection by a combination of the iron chelator 2-furildioxime and sunscreen.

BACKGROUND: Iron is a factor in skin photodamage, apparently by way of its participation in oxygen radical production. Certain topical iron chelators are photoprotective. OBJECTIVE: Our purpose was to determine the level of topical photoprotection provided by the iron chelator 2-furildioxime (FDO) in combination with sunscreen in short- and long-term photoprotection models. METHODS: Guinea pigs were treated topically with FDO, sunscreen, and a combination of the two and were then exposed to varying doses of UV radiation to determine the sun protection factor (SPF). Hairless mice were treated topically with FDO, sunscreen, and a combination of the two and then subjected to long-term exposure to a suberythemal dose of UV radiation. The mice were evaluated for skin wrinkling and skin tumors. RESULTS: In guinea pigs, topical FDO combined with sunscreen provided more than additive protection; 5% FDO alone provides approximately SPF 4, whereas 5% FDO combined with an SPF 4 sunscreen product yielded an SPF of more than 30. In hairless mice exposed long term to UV radiation, 5% FDO and sunscreen delayed tumor onset by a mean of 8 and 12 weeks, respectively. The combination of FDO and sunscreen delayed tumor onset by a mean of 58 weeks. A similar more than additive level of protection was observed for skin wrinkling. CONCLUSION: Topical FDO combined with sunscreen is a potent photoprotection system against both short- and long-term UV radiation exposure.

Administration, Cutaneous↗

PubMed1991

Time-dependent decrease in sunscreen protection against chronic photodamage in UVB-irradiated hairless mouse skin.

To determine the time dependence of sunscreen protection against chronic photodamage in hairless mice, the time was varied (0-8 h) between topical sunscreen treatment and UVB radiation exposure. Sunscreen products with labeled sun protection factor (SPF) values of 2, 4 and 8 were evaluated; these values were verified in a guinea pig model for SPF determinations. When applied immediately prior to UVB radiation exposure, these sunscreen products were very effective in prevention of skin wrinkling and tumor formation. Onset of photodamage was delayed, the delay being greater with higher SPF values. However, the sunscreen actives were rapidly lost from the skin surface, and their protective effect diminished strikingly as the time between treatment and irradiation increased. For daily protection against chronic photodamage, this suggests a need for photoprotectants with greater substantivity to achieve a high level of protection throughout the day.

Animals↗

PubMed1990

Protective effect of topically applied conjugated hexadienes against ultraviolet radiation-induced chronic skin damage in the hairless mouse.

Albino hairless mice (SkH:HR-1) exposed chronically to suberythemal doses of ultraviolet B (UVB) radiation display visible skin wrinkling and tumors. Topical treatment of mice with solutions of conjugated dienes (2,4-hexadien-1-ol and derivatives of it) prior to each UVB radiation exposure reduces significantly the severity of these visible alterations. Chronic suberythemal doses of ultraviolet A radiation induce skin sagging, a distinctly different visible skin alteration. The severity of skin sagging is not reduced by topical application of the conjugated dienes tested here.

Animals↗

PubMed1987

Role of protein and calcium in stratum corneum cell cohesion.

The work reported here indicates that protein and calcium have roles in stratum corneum cell cohesion. A zwitterionic surfactant, 6-octadecyldimethyl ammoniohexanoate (C18AH), was found to completely disaggregate pig and human stratum corneum into intact, individual cells. This method of disaggregation provided a tool to determine the role of tissue components in cell cohesion. The C18AH disaggregation of pig and human stratum corneum was accelerated by proteolytic enzyme and ethylenediaminetetraacetate (EDTA). The C18AH disaggregation could be blocked by pretreatment of the stratum corneum with the serine-type proteolytic enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). The blockage could be overcome by addition of proteolytic enzyme or divalent metal ion chelator. These and other data indicate the importance of protein and calcium in stratum corneum cell cohesion.

Animals↗