Camilla A. Santos
Brown University
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Featured researches published by Camilla A. Santos.
Journal of Controlled Release | 1999
Camilla A. Santos; Jules S. Jacob; Benjamin A. Hertzog; B.D Freedman; D.L Press; P Harnpicharnchai; Edith Mathiowitz
This contribution correlates two in vitro methods utilized to determine bioadhesion. One method, the everted intestinal sac technique, is a passive test for bioadhesion involving several polymer microspheres and a section of everted intestinal tissue. The other method, the CAHN microbalance, employs a CAHN dynamic contact angle analyzer with modified software to record the tensile forces measured as a single polymer microsphere is pulled from intestinal tissue. This study demonstrates that CAHN and everted sac experiments yield similar results when used to quantify the bioadhesive nature of polymer microsphere systems. A polymer showing high adhesion in one method also demonstrates high bioadhesion in the other method; polymers that exhibit high fracture strength and tensile work measurements with the CAHN microbalance also yield high binding percentages with the everted sac method. The polymers tested and reported here are poly(caprolactone) and different copolymer ratios of poly(fumaric-co-sebacic anhydride). The results of this correlation demonstrate that each method alone is a valuable indicator of bioadhesion.
Cancer Immunology, Immunotherapy | 1998
Nejat K. Egilmez; Yong S. Jong; Yoshimi Iwanuma; Jules S. Jacob; Camilla A. Santos; Fang-An Chen; Edith Mathiowitz; Richard B. Bankert
Abstract A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for in vivo cytokine immunotherapy of cancer in a human tumor xenograft/severe combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL-2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the complete suppression of tumor engraftment in 80% of animals. In contrast, bovine-serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of IL-2 released by the microspheres was shown to be mediated by the mouse natural killer cells. This is the first evidence that the rejection of human tumor xenografts can be provoked by the sustained in vivo delivery of IL-2 from biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver cytokines to the tumor environment could provide a safer and simpler alternative to gene therapy protocols in the treatment of cancer.
Journal of Controlled Release | 1999
Camilla A. Santos; B.D Freedman; K.J Leach; D.L Press; Michael A. Scarpulla; Edith Mathiowitz
The degradation of three poly(fumaric-co-sebacic anhydride) [P(FA:SA)] copolymers is examined in a composition of microspheres made by the hot melt encapsulation process. The emergence of low molecular weight oligomers occurs during degradation of the copolymer microspheres, as evidenced by a variety of characterization methods. Characterization was conducted to determine the extent of degradation of the polyanhydride microspheres using Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction. It is demonstrated that degradation of P(FA:SA) is greatly accelerated at basic pH, yet there is little difference between degradation in neutral and acidic buffers. A good correlation exists between the results of each characterization method, which allows a better understanding of the degradation process and the resulting formation of low molecular weight oligomers in poly(fumaric-co-sebacic anhydride).
Biomaterials | 2003
Camilla A. Santos; B.D Freedman; S. Ghosn; J.S Jacob; Michael A. Scarpulla; Edith Mathiowitz
The effect of the addition of small molecular weight anhydride oligomers to polymer microspheres was evaluated and increased bioadhesion of the composite was demonstrated. Blends of low molecular weight anhydride oligomers with thermoplastic poly(fumaric-co-sebacic anhydride) [p(FASA)] and polycaprolactone were examined. The effects of anhydride oligomers on polymer microsphere degradation, crystallinity, and surface morphology were also explored. The results demonstrated that fumaric anhydride oligomer remained within polymer microspheres for several hours after exposure to phosphate buffer, formed a homogenous crystalline blend, increased bioadhesion as measured on rat intestine, and enhanced drug delivery in vitro as measured by the everted sac technique.
MRS Proceedings | 1998
Camilla A. Santos; B.D Freedman; S. Ghosn; Edith Mathiowitz
Bioadhesive polymers are useful as drug delivery systems designed to adhere to the gastrointestinal lumen. The interaction between polymer and mucosal tissue influences residence time of the polymeric device and greatly affects the bioavailability of encapsulated drug. Poly(fumaric-co-sebacic anhydride) [P(FA:SA)] demonstrated impressive results in a variety of in vitro and in vivo experiments designed to test bioadhesion of microspheres. Among different molar ratios of P(FA:SA), adhesive measurements increased with increasing fumaric acid (FA) content. Using a modified microbalance technique, P(FA:SA)10:90 yielded a tensile work measurement of 82.99±12.76 nJ (mean±SEM) while that for P(FA:SA)70:30 was 453.23±47.73 nJ. A low molecular weight substance, fumaric anhydride prepolymer (FAPP), the oligomer form of fumaric acid, was incorporated into the microspheres and greatly increased the bioadhesive properties of P(FA:SA) as well as those of the relatively non-bioadhesive polymer poly(caprolactone) (PCL). Tensile work of P(FA:SA)20:80 was 32.95±5.42 nJ, and P(FA:SA)20:80 with 25% FAPP yielded a tensile work measurement of 556.28±113.12 nJ. Adhesion testing with PCL yielded a tensile work measurement of 7.93±1.84 nJ, while that for PCL with 25% FAPP was 1629.54±307.55 nJ. The effect of FA on drug delivery was evaluated in vitro using the P(FA:SA):FAPP blend with the everted intestinal sac technique. A low molecular weight drug (sodium salicylate) encapsulated in P(FA:SA)20:80 passed through the everted intestinal lumen to the interior of the sac to yield a concentration of 11.17±0.93 mg/dL, and drug encapsulated in P(FA:SA)20:80 with 10% FAPP yielded a concentration of 16.25±1.68 mg/dL (P
Nature | 1997
Edith Mathiowitz; Jules S. Jacob; Yong S. Jong; Gerardo Carino; Donald E. Chickering; Pravin Chaturvedi; Camilla A. Santos; Kavita Vijayaraghavan; Sean Montgomery; Michael J. Bassett; Craig N. Morrell
Archive | 1996
Camilla A. Santos; Jules S. Jacob; Benjamin A. Hertzog; Gerardo Carino; Edith Mathiowitz
Archive | 2004
Jules S. Jacob; Yong S. Jong; Danielle Abramson; Edith Mathiowitz; Camilla A. Santos; Michael J. Bassett; Stacia Furtardo
Archive | 2003
Camilla A. Santos; Jules S. Jacobs; Benjamin A. Hertzog; Gerardo Carino; Edith Mathiowitz
Drugs and the pharmaceutical sciences | 1999
Gerardo Carino; Jules S. Jacob; C. J. Chen; Camilla A. Santos; Benjamin A. Hertzog; Edith Mathiowitz