Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

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Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology†

Biodegradable polymeric nanoparticles based drug delivery systems

Gold nanoparticles in delivery applications

Nanotechnology is the understanding and control of matter generally in the 1-100 nm dimension range. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as ultra small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents.

Nanoparticles in Medicine: Therapeutic Applications and Developments

Active targeting schemes for nanoparticle systems in cancer therapeutics.

Nanoparticle and targeted systems for cancer therapy.

In recent years there has been significant new interest in the development of transmucosal (mostly oral) pharmaceutical formulations for the delivery of therapeutic proteins. Emphasis has been given to the molecular design of new carriers for the delivery of insulin, calcitonin and various types of interferons for the treatment of diabetes, osteoporosis, multiple sclerosis and cancer. Most popular carriers include advanced designs of swollen hydrogels prepared from neutral or intelligent polymeric networks. In this review, the most successful of such systems are presented and their promise in the field described.

Hydrogels for oral delivery of therapeutic proteins.

Principles of transmucosal delivery of therapeutic agents

Purpose: The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment. Experimental Design: RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples. Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent growth. Results: Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers. The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer libraries (P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production, reduction in cell growth (P < 0.002), decrease in the S-phase fraction (P < 0.04), and loss of density-independent growth potential (P < 0.01). Conclusion: cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects of its antisense down-regulation suggest that GEP may be a new autocrine growth factor and molecular target for epithelial ovarian cancer.

https://clincancerres.aacrjournals.org/content/clincanres/9/1/44.full.pdf

The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer

Human mesenchymal stem cells (hMSCs) were infected with an adenovirus expressing integrin-linked kinase (ILK) to understand the role of cell-ECM signal transduction cascades in suppressing anoikis. Survivability of ILK-infected hMSCs encapsulated in poly(ethylene glycol) (PEG) hydrogels, an anoikis-inducing environment, was sustained at 90% over 7 weeks, and survival was attributed to increased protein kinase B (PKB/Akt) activation. hMSCs encapsulated in RGD-modified hydrogels induced an upregulation in ILK production, PKB/Akt activation, and subsequent survival to the same extent of ILK-infected, encapsulated hMSCs. As negative controls, encapsulated hMSCs were infected with cyclization recombinase (a protein not associated with cell survival)-expressing virus, and uninfected hMSCs exhibited very little ILK production, PKB/Akt activation, and survival (∼55% after 7 weeks). As a measure of cell–matrix interactions, vinculin was also quantified for the encapsulated hMSCs and found to be 30-fold greater for cells encapsulated in RGD-modified hydrogels and fivefold greater for ILK-infected hMSCs than controls, indicating that cell–material interactions are inducing the cell survivability of hMSCs encapsulated in RGD-modified hydrogels. In sum, ILK infection can support cell survival in the absence of matrix interactions and enable fundamental studies of three-dimensional cell function in response to extrinsic signals, independently of matrix–ligand interactions. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

James O. Blanchette

Papers

Nanoparticle and targeted systems for cancer therapy.

Hydrogels for oral delivery of therapeutic proteins.

Principles of transmucosal delivery of therapeutic agents

The Granulin-Epithelin Precursor/PC-Cell-derived Growth Factor Is a Growth Factor for Epithelial Ovarian Cancer

Integrin-linked kinase production prevents anoikis in human mesenchymal stem cells.