Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00094-L
Bilha Schechter , Ruth Arnon , Meir Wilchek
Cisplatin (CDDP), a most powerful anticancer agent, was complexed to a polycarboxylic carrier carboxymethyldextran to form a platinum(II) multicomplex. Complexing occurs by displacement of the chlorine atoms of the platinum coordination complex by hydrogen of polymer side-chains to form mono- or bifunctional anchoring to adjacent carboxyls on the carrier. The carrier-complexed drug interacted with DNA and was pharmacologically active against tumor cells. The drug-carrier complex was immunotargeted to human epidermoid carcinoma (KB) tumors, using the monoclonal antibody (mAb) 108 directed against the epidermal growth factor receptor that is overexpressed on KB cells. Biotinyl-monoclonal antibody was bound to a platinum(II)-carboxymethyldextran-avidin conjugate and the immune complex was administered into established subcutaneous KB tumors to evaluate its effects upon intratumor treatment. The results showed that the immune complex was specifically effective in inhibiting tumor growth. The antibody in the complex must be tumor-specific to anchor the drug-carrier multicomplex to the tumor site since an unbiotinylated antibody, or replacing the anti-KB antibody by a biotinylated antibody of a different specificity, resulted in reduced or abolished inhibitory effects.
{"title":"Polymers in drug delivery: immunotargeting of carrier-supported cis-platinum complexes","authors":"Bilha Schechter , Ruth Arnon , Meir Wilchek","doi":"10.1016/0923-1137(94)00094-L","DOIUrl":"10.1016/0923-1137(94)00094-L","url":null,"abstract":"<div><p>Cisplatin (CDDP), a most powerful anticancer agent, was complexed to a polycarboxylic carrier carboxymethyldextran to form a platinum(II) multicomplex. Complexing occurs by displacement of the chlorine atoms of the platinum coordination complex by hydrogen of polymer side-chains to form mono- or bifunctional anchoring to adjacent carboxyls on the carrier. The carrier-complexed drug interacted with DNA and was pharmacologically active against tumor cells. The drug-carrier complex was immunotargeted to human epidermoid carcinoma (KB) tumors, using the monoclonal antibody (mAb) 108 directed against the epidermal growth factor receptor that is overexpressed on KB cells. Biotinyl-monoclonal antibody was bound to a platinum(II)-carboxymethyldextran-avidin conjugate and the immune complex was administered into established subcutaneous KB tumors to evaluate its effects upon intratumor treatment. The results showed that the immune complex was specifically effective in inhibiting tumor growth. The antibody in the complex must be tumor-specific to anchor the drug-carrier multicomplex to the tumor site since an unbiotinylated antibody, or replacing the anti-KB antibody by a biotinylated antibody of a different specificity, resulted in reduced or abolished inhibitory effects.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 167-175"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00094-L","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82679824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(95)00050-S
Elazer R Edelman
Heparin is the gold standard growth inhibitor for vascular smooth muscle cells, with chemistry and bioactivity similar to endogenous reparative compounds, such as heparan sulfate. Thus, heparin should be especially effective against proliferative arterial diseases that involve smooth muscle cells. Yet, at the systemic doses tolerated intermittent subcutaneous injections or intravenous infusion have, if anything, exacerbated rather than alleviated disease. We have demonstrated that far more beneficial effects are observed if one matches the delivery of heparin to the natural release of endogenous growth regulators; namely in a continuous manner, administered directly to specific injured segments of the blood vessel wall. Local, perivascular controlled release of heparin from polymeric matrices inhibited smooth muscle cell proliferation following injury to vascular endothelium: for anticoagulant heparin without the need for systemic anticoagulation; for anticoagulant heparin when administered from a site distant from the injured vessel; and in a manner more efficient than in systemic administration. Some heparin compounds only achieved a therapeutic response when delivered from polymeric devices in the perivascular position.
These results lay the groundwork for examining the local control of the vascular response to injury and for investigating site specific means of modulating these processes. Polymeric drug delivery systems offer the potential for novel therapies and a means of investigating complex disease states. Future work on materials, formulations, and pharmacokinetics will aid immensely in these regards.
{"title":"Perivascular delivery of heparin regulates myointimal hyperplasia","authors":"Elazer R Edelman","doi":"10.1016/0923-1137(95)00050-S","DOIUrl":"10.1016/0923-1137(95)00050-S","url":null,"abstract":"<div><p>Heparin is the gold standard growth inhibitor for vascular smooth muscle cells, with chemistry and bioactivity similar to endogenous reparative compounds, such as heparan sulfate. Thus, heparin should be especially effective against proliferative arterial diseases that involve smooth muscle cells. Yet, at the systemic doses tolerated intermittent subcutaneous injections or intravenous infusion have, if anything, exacerbated rather than alleviated disease. We have demonstrated that far more beneficial effects are observed if one matches the delivery of heparin to the natural release of endogenous growth regulators; namely in a continuous manner, administered directly to specific injured segments of the blood vessel wall. Local, perivascular controlled release of heparin from polymeric matrices inhibited smooth muscle cell proliferation following injury to vascular endothelium: for anticoagulant heparin without the need for systemic anticoagulation; for anticoagulant heparin when administered from a site distant from the injured vessel; and in a manner more efficient than in systemic administration. Some heparin compounds only achieved a therapeutic response when delivered from polymeric devices in the perivascular position.</p><p>These results lay the groundwork for examining the local control of the vascular response to injury and for investigating site specific means of modulating these processes. Polymeric drug delivery systems offer the potential for novel therapies and a means of investigating complex disease states. Future work on materials, formulations, and pharmacokinetics will aid immensely in these regards.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 149-156"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(95)00050-S","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74062831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00095-M
S Brandriss , G Borchardt , J Kreuter , S Margel
The synthesis and characterization of new radiolabeled 75Se-silica nanoparticles are described. These particles have been prepared by dispersion polymerization of tetraethylorthosilicate in ethanol in presence of radiolabeled 75selenium-colloids. The amount of Se-colloids encapsulated within the silica matrix was then increased by two successive seeded polymerizations of tetraethylorthosilicate on the previously formed particles. Kinetic studies and the effect of various factors, i.e. sodium selenite, water and ammonium hydroxide concentrations, on the diameter of these nanoparticles have been elucidated. The Se-silica nanoparticles have been covalently coated by the self-assembled technique with a variety of ω-functionalized alkylsilane compounds. Characterization of these coatings has been performed by Fourier transform-infrared spectroscopy, elemental analysis and floatability studies. The potential use of these varieties of ω-functionalized radiolabeled nanoparticles for drug delivery purposes has been demonstrated in a separate article.
{"title":"Radiolabeled 75Se-silica nanoparticles: synthesis, characterization and coating with ω-functionalized alkylsilane compounds","authors":"S Brandriss , G Borchardt , J Kreuter , S Margel","doi":"10.1016/0923-1137(94)00095-M","DOIUrl":"10.1016/0923-1137(94)00095-M","url":null,"abstract":"<div><p>The synthesis and characterization of new radiolabeled <sup>75</sup>Se-silica nanoparticles are described. These particles have been prepared by dispersion polymerization of tetraethylorthosilicate in ethanol in presence of radiolabeled <sup>75</sup>selenium-colloids. The amount of Se-colloids encapsulated within the silica matrix was then increased by two successive seeded polymerizations of tetraethylorthosilicate on the previously formed particles. Kinetic studies and the effect of various factors, i.e. sodium selenite, water and ammonium hydroxide concentrations, on the diameter of these nanoparticles have been elucidated. The Se-silica nanoparticles have been covalently coated by the self-assembled technique with a variety of ω-functionalized alkylsilane compounds. Characterization of these coatings has been performed by Fourier transform-infrared spectroscopy, elemental analysis and floatability studies. The potential use of these varieties of ω-functionalized radiolabeled nanoparticles for drug delivery purposes has been demonstrated in a separate article.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 111-125"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00095-M","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84110557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00098-P
D.E Chickering III, J.S Jacob, E Mathiowitz
Several bioerodible polymers and one hydrogel were studied as potential bioadhesive materials. A microbalance-based method was used to measure bioadhesive interactions between individual polymer microspheres and rat intestinal tissue. In addition, surface and bulk properties of these microspheres were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle measurements. Polyanhydride microspheres composed of copolymers of fumaric and sebacic acid, produced bioadhesive fracture strengths greater than 50 mN/cm2 with rat small intestinal mucosa in vitro. We suggest that bioadhesion in these bioerodible materials is not attributable to chain entanglement, but instead to hydrogen bonding between hydrophilic functional groups (COOH) and mucus glycoproteins. We also believe that continuous degradation of these materials may enhance their bioadhesive properties by changing surface energy, and increasing both carboxylic acid concentration and surface roughness.
{"title":"Bioadhesive microspheres, II. Characterization and evaluation of bioadhesion involving hard, bioerodible polymers and soft tissue","authors":"D.E Chickering III, J.S Jacob, E Mathiowitz","doi":"10.1016/0923-1137(94)00098-P","DOIUrl":"10.1016/0923-1137(94)00098-P","url":null,"abstract":"<div><p>Several bioerodible polymers and one hydrogel were studied as potential bioadhesive materials. A microbalance-based method was used to measure bioadhesive interactions between individual polymer microspheres and rat intestinal tissue. In addition, surface and bulk properties of these microspheres were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle measurements. Polyanhydride microspheres composed of copolymers of fumaric and sebacic acid, produced bioadhesive fracture strengths greater than 50 mN/cm<sup>2</sup> with rat small intestinal mucosa in vitro. We suggest that bioadhesion in these bioerodible materials is not attributable to chain entanglement, but instead to hydrogen bonding between hydrophilic functional groups (COOH) and mucus glycoproteins. We also believe that continuous degradation of these materials may enhance their bioadhesive properties by changing surface energy, and increasing both carboxylic acid concentration and surface roughness.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 189-206"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00098-P","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77472571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00097-O
Frank T Gentile, Edward J Doherty, David H Rein, Molly S Shoichet, Shelley R Winn
The goal of encapsulated cell therapy research is to develop implants containing living xenogeneic cells to treat serious and disabling human conditions. The enabling concept is straightforward: cells or small clusters of tissue are surrounded by a selective membrane barrier which admits oxygen and required metabolites, releases bioactive cell secretions but restricts the transport of the larger cytotoxic agents of the body's immune defense system. Use of a selective membrane both eliminates the need for chronic immunosuppression in the host and allows cells to be obtained from non-human sources, thus avoiding the cell-sourcing constraints which have limited the clinical application of general successful investigative trials of unencapsulated cell transplantation for chronic pain, Parkinson's disease, and type I diabetes. Target applications for encapsulated cell therapy include these same disorders as well as other disabilities caused by loss of secretory cell function which cannot be adequately treated by current organ transplantation or drug therapies and conditions potentially capable of responding to local sustained delivery of growth factors and other biologic response modifiers. Several types of device configurations are possible. Here we focus on easily retrieved, non-vascularized, macrocapsules. Such devices have four basic components: a hollow fiber or flat sheet membrane (usually thermoplastic based), cells (primary or dividing), and extracellular matrix (natural or synthetic) to promote cell viability and function, and other device components such as seals, tethers and radio-opaque markers. Choice of membrane and extracellular matrix polymers as well as issues surrounding implantation and biocompatibility evaluation are complex, inter-related, and ultimately driven by implantation site and delivery requirements. Cross species immunoisolated cell therapy has been validated small and large animal models of chronic pain, Parkinson's disease, and type 1 diabetes and is under active investigation by several groups in animal models of Huntington's, Hemophilia, Alzheimer's, ALS, and other CNS disorders.
{"title":"Polymer science for macroencapsulation of cells for central nervous system transplantation","authors":"Frank T Gentile, Edward J Doherty, David H Rein, Molly S Shoichet, Shelley R Winn","doi":"10.1016/0923-1137(94)00097-O","DOIUrl":"10.1016/0923-1137(94)00097-O","url":null,"abstract":"<div><p>The goal of encapsulated cell therapy research is to develop implants containing living xenogeneic cells to treat serious and disabling human conditions. The enabling concept is straightforward: cells or small clusters of tissue are surrounded by a selective membrane barrier which admits oxygen and required metabolites, releases bioactive cell secretions but restricts the transport of the larger cytotoxic agents of the body's immune defense system. Use of a selective membrane both eliminates the need for chronic immunosuppression in the host and allows cells to be obtained from non-human sources, thus avoiding the cell-sourcing constraints which have limited the clinical application of general successful investigative trials of <em>unencapsulated</em> cell transplantation for chronic pain, Parkinson's disease, and type I diabetes. Target applications for encapsulated cell therapy include these same disorders as well as other disabilities caused by loss of secretory cell function which cannot be adequately treated by current organ transplantation or drug therapies and conditions potentially capable of responding to local sustained delivery of growth factors and other biologic response modifiers. Several types of device configurations are possible. Here we focus on easily retrieved, non-vascularized, macrocapsules. Such devices have four basic components: a hollow fiber or flat sheet membrane (usually thermoplastic based), cells (primary or dividing), and extracellular matrix (natural or synthetic) to promote cell viability and function, and other device components such as seals, tethers and radio-opaque markers. Choice of membrane and extracellular matrix polymers as well as issues surrounding implantation and biocompatibility evaluation are complex, inter-related, and ultimately driven by implantation site and delivery requirements. Cross species immunoisolated cell therapy has been validated small and large animal models of chronic pain, Parkinson's disease, and type 1 diabetes and is under active investigation by several groups in animal models of Huntington's, Hemophilia, Alzheimer's, ALS, and other CNS disorders.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 207-227"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00097-O","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88154697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00039-8
M.A Wheatley, S Singhal
Ultrasound is a noninvasive tool with which the physician can gain insight into the state of the internal organs of the body. A contrast agent is a substance which, when injected into the body improves the resolution of an image. The use of diagnostic ultrasound is limited without development of such an agent. This paper describes the development of a new class of contrast agent. The agent consists of microbubbles generated in a solution by sonication, and stabilized by a layer of nonionic surfactant molecules. A single surfactant type alone does not produce stable bubbles, and only certain combinations of surfactants, one with a hydrophile-lipophile balance (HLB) greater than 10.5 and the other with an HLB less than 9, are successful. An agent prepared from Span60® and Tween80® is described in detail. A Coulter analysis revealed that 90% of the bubbles were less than 10 μm in diameter. This is essential if the agent is to pass the pulmonary capillary bed. B-mode imaging of a sample of microbubbles indicated that these bubbles were highly echogenic (that is they produced a strong contrast). A Langmuir trough study of the molecular arrangement of the surfactant molecules inside the microbubble skin suggested that there are 1.7 molecules of Span to each Tween molecule. Detailed analysis of the pressure-area curves and area per molecule data lead to the hypothesis that the correct proportion of Span molecules can substantially reduce the head group repulsion found in the all-Tween situation, and this results in the generation of stable microbubbles. A molecular arrangement of these surfactant molecules around the microbubble is proposed.
{"title":"Structural studies on stabilized microbubbles: development of a novel contrast agent for diagnostic ultrasound","authors":"M.A Wheatley, S Singhal","doi":"10.1016/0923-1137(94)00039-8","DOIUrl":"10.1016/0923-1137(94)00039-8","url":null,"abstract":"<div><p>Ultrasound is a noninvasive tool with which the physician can gain insight into the state of the internal organs of the body. A contrast agent is a substance which, when injected into the body improves the resolution of an image. The use of diagnostic ultrasound is limited without development of such an agent. This paper describes the development of a new class of contrast agent. The agent consists of microbubbles generated in a solution by sonication, and stabilized by a layer of nonionic surfactant molecules. A single surfactant type alone does not produce stable bubbles, and only certain combinations of surfactants, one with a hydrophile-lipophile balance (HLB) greater than 10.5 and the other with an HLB less than 9, are successful. An agent prepared from Span60® and Tween80® is described in detail. A Coulter analysis revealed that 90% of the bubbles were less than 10 μm in diameter. This is essential if the agent is to pass the pulmonary capillary bed. B-mode imaging of a sample of microbubbles indicated that these bubbles were highly echogenic (that is they produced a strong contrast). A Langmuir trough study of the molecular arrangement of the surfactant molecules inside the microbubble skin suggested that there are 1.7 molecules of Span to each Tween molecule. Detailed analysis of the pressure-area curves and area per molecule data lead to the hypothesis that the correct proportion of Span molecules can substantially reduce the head group repulsion found in the all-Tween situation, and this results in the generation of stable microbubbles. A molecular arrangement of these surfactant molecules around the microbubble is proposed.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 157-166"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00039-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78300985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(95)91297-P
B.I Dahiyat, E.M Posadas, S Hirosue, E Hostin, K.W Leong
The design of drug-carrying elastomers based on poly(phosphoester-urethanes) (PPUs) is presented. Bis(2-hydroxyethyl)phosphite and bis(6-hydroxyhexyl)phosphite were used as the chain extenders and 1,4-butane diisocyanate was the basis of the hard segment. The labile phosphoester linkage in the backbone of the PPU confers biodegradability on the polymer. Using the reactive phosphite side chain in the PPUs, p-aminosalicylic acid and benzocaine were attached pendantly to the polymer with or without a spacer. In vitro release of both drugs was complete in several hours. In contrast, ethambutol incorporated into the backbone of the polymer was released in over 10 days. Preliminary cytotoxicity of the drug-carrier to a macrophage cell line was also assessed.
{"title":"Degradable biomaterials with elastomeric characteristics and drug-carrier function","authors":"B.I Dahiyat, E.M Posadas, S Hirosue, E Hostin, K.W Leong","doi":"10.1016/0923-1137(95)91297-P","DOIUrl":"10.1016/0923-1137(95)91297-P","url":null,"abstract":"<div><p>The design of drug-carrying elastomers based on poly(phosphoester-urethanes) (PPUs) is presented. Bis(2-hydroxyethyl)phosphite and bis(6-hydroxyhexyl)phosphite were used as the chain extenders and 1,4-butane diisocyanate was the basis of the hard segment. The labile phosphoester linkage in the backbone of the PPU confers biodegradability on the polymer. Using the reactive phosphite side chain in the PPUs, <em>p</em>-aminosalicylic acid and benzocaine were attached pendantly to the polymer with or without a spacer. In vitro release of both drugs was complete in several hours. In contrast, ethambutol incorporated into the backbone of the polymer was released in over 10 days. Preliminary cytotoxicity of the drug-carrier to a macrophage cell line was also assessed.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 101-109"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(95)91297-P","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85492463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(95)00043-I
Smadar Cohen , Limor Chen , Ron N Apte
An approach to enhance the immunogenicity of peptide-based vaccines for malaria and the immunoregulatory activity of recombinant human interleukin-1α (IL-1) is described. The approach involves the encapsulation of these molecules in, and their controlled release from, biodegradable polyester microspheres of lactic and glycolic acids (PLGA). The microspheres are prepared by the modified solvent evaporation method based on a double emulsion. Two types of microspheres composed of PLGA (75:25 lactic/glycolic acid) and of different MW were constructed for each molecule. The release characteristics of these molecules from these microspheres were evaluated using spectroscopy and bioactivity assays. In vivo studies established the feasibility of PLGA carriers as an immunization vehicle for malaria peptide-based vaccines; the induced immune responses in mice were stronger than those obtained with peptide in complete Freund's adjuvant. In addition, these studies provide preliminary evidence that PLGA microspheres with encapsulated IL-1 can be used as a new strategy for the efficient delivery of this cytokine to tumor sites in immunotherapy.
{"title":"Controlled release of peptides and proteins from biodegradable polyester microspheres: an approach for treating infectious diseases and malignancies","authors":"Smadar Cohen , Limor Chen , Ron N Apte","doi":"10.1016/0923-1137(95)00043-I","DOIUrl":"10.1016/0923-1137(95)00043-I","url":null,"abstract":"<div><p>An approach to enhance the immunogenicity of peptide-based vaccines for malaria and the immunoregulatory activity of recombinant human interleukin-1α (IL-1) is described. The approach involves the encapsulation of these molecules in, and their controlled release from, biodegradable polyester microspheres of lactic and glycolic acids (PLGA). The microspheres are prepared by the modified solvent evaporation method based on a double emulsion. Two types of microspheres composed of PLGA (75:25 lactic/glycolic acid) and of different MW were constructed for each molecule. The release characteristics of these molecules from these microspheres were evaluated using spectroscopy and bioactivity assays. In vivo studies established the feasibility of PLGA carriers as an immunization vehicle for malaria peptide-based vaccines; the induced immune responses in mice were stronger than those obtained with peptide in complete Freund's adjuvant. In addition, these studies provide preliminary evidence that PLGA microspheres with encapsulated IL-1 can be used as a new strategy for the efficient delivery of this cytokine to tumor sites in immunotherapy.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 177-187"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(95)00043-I","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84816754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00040-C
M.T am Ende , D Hariharan , N.A Peppas
The effect of polymer structural parameters of ionic hydrogels on the transport of drugs and proteins has been studied for a number of anionic and cationic hydrogels. Crosslinked anionic hydrogels were composed of acrylic acid and 2-hydroxyethyl methacrylate, whereas cationic hydrogels were based on diethyl aminoethyl acrylate or diethyl aminoethyl methacrylate and 2-hydroxyethyl methacrylate. The hydrogel structure was investigated using dynamic swelling studies to deduce the variation of mesh size available for solute transport as a function of environmental parameters including the pH and ionic strength. For anionic hydrogels, the mesh size increased with increasing pH due to the ionization of the network. The reverse was true for cationic hydrogels. Ionizable drugs and proteins could interact with the ionizable hydrogels during the transport process. The solute size also affected the release behavior, causing additional hindrance and decreased mobility.
{"title":"Factors influencing drug and protein transport and release from ionic hydrogels","authors":"M.T am Ende , D Hariharan , N.A Peppas","doi":"10.1016/0923-1137(94)00040-C","DOIUrl":"10.1016/0923-1137(94)00040-C","url":null,"abstract":"<div><p>The effect of polymer structural parameters of ionic hydrogels on the transport of drugs and proteins has been studied for a number of anionic and cationic hydrogels. Crosslinked anionic hydrogels were composed of acrylic acid and 2-hydroxyethyl methacrylate, whereas cationic hydrogels were based on diethyl aminoethyl acrylate or diethyl aminoethyl methacrylate and 2-hydroxyethyl methacrylate. The hydrogel structure was investigated using dynamic swelling studies to deduce the variation of mesh size available for solute transport as a function of environmental parameters including the pH and ionic strength. For anionic hydrogels, the mesh size increased with increasing pH due to the ionization of the network. The reverse was true for cationic hydrogels. Ionizable drugs and proteins could interact with the ionizable hydrogels during the transport process. The solute size also affected the release behavior, causing additional hindrance and decreased mobility.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 127-137"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00040-C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82173702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1995-06-01DOI: 10.1016/0923-1137(94)00096-N
Jennifer L West , Jeffrey A Hubbell
A novel photopolymerized hydrogel material has been developed for use as a drug delivery vehicle for bioactive materials. The hydrogel precursor consists of polyethylene glycol copolymerized with an α-hydroxy acid and with acrylate termini at each end. The precursor is water-soluble and non-toxic. The precursor polymerization conditions are very mild, and polymerization can be carried out in direct contact with cells and tissues. The degradation rate and permeability of the hydrogel can be altered by changing the composition of the precursors, allowing use of this class of materials for a variety of applications. In vitro release of proteins and oligonucleotides is reported.
{"title":"Photopolymerized hydrogel materials for drug delivery applications","authors":"Jennifer L West , Jeffrey A Hubbell","doi":"10.1016/0923-1137(94)00096-N","DOIUrl":"10.1016/0923-1137(94)00096-N","url":null,"abstract":"<div><p>A novel photopolymerized hydrogel material has been developed for use as a drug delivery vehicle for bioactive materials. The hydrogel precursor consists of polyethylene glycol copolymerized with an α-hydroxy acid and with acrylate termini at each end. The precursor is water-soluble and non-toxic. The precursor polymerization conditions are very mild, and polymerization can be carried out in direct contact with cells and tissues. The degradation rate and permeability of the hydrogel can be altered by changing the composition of the precursors, allowing use of this class of materials for a variety of applications. In vitro release of proteins and oligonucleotides is reported.</p></div>","PeriodicalId":20864,"journal":{"name":"Reactive Polymers","volume":"25 2","pages":"Pages 139-147"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0923-1137(94)00096-N","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84756603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}