Sustained Release Studies of Metformin Hydrochloride Drug Using Conducting Polymer/Gelatin-Based Composite Hydrogels.

The present work highlights the synthesis and characterization of conducting polymer (CP)-based composite hydrogels with gelatin (GL-B) for their application as drug delivery vehicles. The spectral, morphological, and rheological properties of the synthesized hydrogels were explored, and morphological studies confirmed formation of an intense interpenetrating network. Rheological measurements showed variation in the flow behavior with the type of conducting polymer. The hydrogels showed a slow drug release rate of about 10 h due to the presence of the conducting polymer. The release kinetics were fitted in various mathematical models and were best fit in first order for PNA-, POPD-, and PANI-based GL-B hydrogels, and the PVDF/GL-B hydrogel was best fit in the zero-order models. The drug release was found to follow the order: POPD/GL-B > PANI/GL-B > PVDF/GL-B.

Linear and nonlinear rheology of liberase-treated breast cancer tumors.

Extracellular matrix (ECM) rigidity has been shown to increase the invasive properties of breast cancer cells, promoting transformation and metastasis through mechanotransduction. Reducing ECM stiffness via enzymatic digestion could be a promising approach to slowing breast cancer development by de-differentiation of breast cancer cells to less aggressive phenotypes and enhancing the effectiveness of existing chemotherapeutics via improved drug penetrance throughout the tumor. In this study, we examine the effects of injectable liberase (a blend of collagenase and thermolysin enzymes) treatments on the linear and nonlinear rheology of allograft 4T1 mouse mammary tumors. We perform two sets of in vivo mouse studies, in which either one or multiple treatment injections occur before the tumors are harvested for rheological analysis. The treatment groups in each study consist of a buffer control, free liberase enzyme in buffer, a thermoresponsive copolymer called LiquoGel (LQG) in buffer, and a combined, localized injection of LQG and liberase. All tumor samples exhibit gel-like linear rheological behavior with the elastic modulus significantly larger than the viscous modulus and both independent of frequency. Tumors that receive a single injection of localized liberase have significantly lower tumor volumes and lower tissue moduli at both the center and edge compared to buffer- and free liberase-injected control tumors, while tissue viscoelasticity remains relatively unaffected. Tumors injected multiple times with LQG and liberase also have lower tissue volumes but possess higher tissue moduli and lower viscoelasticities compared to the other treatment groups. We propose that a mechanotransductive mechanism could cause the formation of smaller but stiffer tumors after repeated, localized liberase injections. Large amplitude oscillatory shear (LAOS) experiments are also performed on tissues from the multiple injection study and the results are analyzed using MITlaos. LAOS analysis reveals that all 4T1 tumors from the multiple injection study exhibit nonlinear rheological behavior at high strains and strain rates. Examination of the Lissajous-Bowditch curves, Chebyshev coefficient ratios, elastic moduli, and dynamic viscosities demonstrate that the onset and type of nonlinear behavior is independent of treatment type and elastic modulus, suggesting that multiple liberase injections do not affect the nonlinear viscoelasticity of 4T1 tumors.

Treatment for Uterine Fibroids: Searching for Effective Drug Therapies.

Uterine fibroids are common reproductive-age benign tumors that contribute to severe morbidity and infertility. Cumulative incidence is 4 times higher in Africian-Americans compared to Caucasians and constitutes a major health disparity challenge. Fibroids are the leading indication for hysterectomy and their management averages $21 billion annually in the US. No long term minimally invasive therapies exist. Thus, promising drug therapies, their chemistry, pharmacology, and clinical efficacy, focusing first on innovative drug delivery approaches, are reviewed.

Recent advances in the utilization of polyaniline in protein detection: a short review.

Various reports have been published based on covalently attaching biomolecules to polyaniline (PANI). The functional groups connected to the surface of polymeric units determine the immobilization method as well as the method of detection. The present mini-review aims at covering recent advances in the field of protein binding and detection using PANI. Several proteins have been attached to the polymer using different immobilization techniques. The application of PANI in protein detection has also been discussed along with the future scope of these materials in diagnosis and detection.

Using rheology to quantify the effects of localized collagenase treatments on uterine fibroid digestion.

Uterine fibroids are stiff, benign tumors containing excessive, disordered collagens that occur in 70-80% of women before age 50 and cause bleeding and pain. Collagenase Clostridium histolyticum (CCH) is a bacterial enzyme capable of digesting the collagens present in fibroids. By combining CCH with injectable drug delivery systems to enhance effectiveness, a new class of treatments could be developed to reduce the stiffness of fibroids, preventing the need for surgical removal and preserving fertility. In this work, we achieved localization of CCH via physical entrapment by co-injecting a thermoresponsive pNIPAM-based polymeric delivery system called LiquoGel (LQG), which undergoes a sol-gel transition upon heating. Toxicity study results for LQG injected subcutaneously into mice demonstrate that LQG does not induce lesions or other adverse effects. We then used rheology to quantify the effects of localized CCH injections on the modulus and viscoelasticity of uterine fibroids, which exhibit gel-like behavior, through ex vivo and in vivo digestion studies. Ex vivo CCH injections reduce the tissue modulus by over two orders of magnitude and co-injection of LQG enhances this effect. Rheological results from an in vivo digestion study in mice show a significant reduction in tissue modulus and increase in tissue viscoelasticity 7 days after a single injection of LQG+CCH. Parallel histological staining validates that the observed rheological changes correspond to an increase in collagen lysis after treatment by LQG+CCH. These results show promise for development of injectable and localized enzymatic therapies for uterine fibroids and other dense tumors. STATEMENT OF SIGNIFICANCE: Uterine fibroids are stiff, benign tumors containing high collagen levels that cause bleeding and pain in women. Fertility-preserving and minimally-invasive treatments to soften fibroids are needed as an alternative to surgical removal via hysterectomy. We demonstrate through ex vivo and in vivo studies that co-injecting a thermoresponsive polymer delivery system (LQG) alongside a bacterial collagenase (CCH) enzyme significantly increases treatment effectiveness at softening fibroids through CCH localization. We use rheology to measure the modulus and viscoelasticity of fibroids and histology to show that fibroid softening corresponds to a decrease in collagen after treatment with LQG+CCH. These results highlight the utility of rheology at quantifying tissue properties and present a promising injectable therapy for fibroids and other dense tumors.

Effect of substitution on the optical properties and HOMO-LUMO gap of oligomeric paraphenylenes.

A series of dialkyl amino benzophenone dimers with various alkyl chain lengths is presented. Gaussian B3LYP/6-31G(d) calculations show that the band gap decreases within the dimer series as a function of the donor group efficiency. Theoretical calculations show that the interaction between phenyl-phenyl rings is more important than simple donor-acceptor effects. We report the experimental and electro-optical properties of one of these dimers, N,N-(dibutyl)-4-amino-benzophenone. The experimental and theoretical results enabled us to design a new dimer. Altogether, side chain substituents reported herein tune the theoretical band gap of paraphenylene based dimers by over 8.86 eV.

In Situ Drug Delivery to Breast Cancer-Associated Extracellular Matrix.

The extracellular matrix (ECM) contributes to tumor progression through changes induced by tumor and stromal cell signals that promote increased ECM density and stiffness. The increase in ECM stiffness is known to promote tumor cell invasion into surrounding tissues and metastasis. In addition, this scar-like ECM creates a protective barrier around the tumor that reduces the effectiveness of innate and synthetic antitumor agents. Herein, clinically approved breast cancer therapies as well as novel experimental approaches that target the ECM are discussed, including in situ hydrogel drug delivery systems, an emerging technology the delivers toxic chemotherapeutics, gene-silencing microRNAs, and tumor suppressing immune cells directly inside the tumor. Intratumor delivery of therapeutic agents has the potential to drastically reduce systemic side effects experienced by the patient and increase the efficacy of these agents. This review also describes the opposing effects of ECM degradation on tumor progression, where some studies report improved drug delivery and delayed cancer progression and others report enhanced metastasis and decreased patient survival. Given the recent increase in ECM-targeting drugs entering preclinical and clinical trials, understanding and addressing the factors that impact the effect of the ECM on tumor progression is imperative for the sake of patient safety and survival outcome.

Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management.

Uterine leiomyomas (fibroids) are the most prevalent medical problem of the female reproductive tract, but there are few non-surgical treatment options. Although many advances in the understanding of the molecular components of these tumors have occurred over the past five years, an effective pharmaceutical approach remains elusive. Further, there is currently no clinical method to distinguish a benign uterine leiomyoma from a malignant leiomyosarcoma prior to treatment, a pressing need given concerns about the use of the power morcellator for minimally invasive surgery. This paper reviews current studies regarding the molecular biology of uterine fibroids, discusses non-surgical approaches and suggests new cutting-edge therapeutic and diagnostic approaches.

Soluble reduced graphene oxide sheets grafted with polypyridylruthenium-derivatized polystyrene brushes as light harvesting antenna for photovoltaic applications.

Soluble graphene nanosheets, prepared by grafting polystyrene-based polymer chains from the surface of reduced graphene oxide (RGO), have been functionalized with pendant Ru(II) polypyridine chromophores. N-Hydroxysuccinimide (NHS) derivatized p-vinylbenzoic acid polymer chains were grown from methyl bromoisobutyrate initiation sites on the surface of RGO by atom transfer radical polymerization (ATRP). Deprotection of the resulting NHS polystyrene chains followed by amide coupling with the amine-derivatized Ru(II) polypyridyl complex [Ru(4-CH2NH2-4'-CH3-bpy)(bpy)2](2+) (4-CH2NH2-4'-CH3-bpy = 4-aminomethyl-4'-methyl 2,2'-bipyridine and bpy = 2,2'-bipyridine) afforded the covalently linked RGO-metallopolymer. The hybrid graphene-polymer assembly has been fully characterized with clear evidence for covalent attachment of the metallopolymer brushes to the graphene substrate. On the basis of thermal gravimetric analysis, one polymer strand is grafted to the surface of RGO for every hundred graphene carbons. The covalently linked polymer brushes feature controlled chain lengths of ∼30 repeat units with a small polydispersity index (PDI, ∼ 1.2). Photovoltaic cells based on the derivatized polymers and graphene-polymer assemblies were evaluated. The graphene-polymer assembly in the configuration, ITO/PEDOT:PSS/RGO-PSRu/PC60BM/Al, exhibited enhanced photocurrent and power conversion efficiencies (∼5 fold) relative to devices with the configuration, ITO/PEDOT:PSS/PSRu/PC60BM/Al.

Temperature-responsive biocompatible copolymers incorporating hyperbranched polyglycerols for adjustable functionality.

Temperature-triggered copolymers are proposed for a number of bio-applications but there is no ideal material platform, especially for injectable drug delivery. Options are needed for degradable biomaterials that not only respond to temperature but also easily accommodate linkage of active molecules. A first step toward realizing this goal is the design and synthesis of the novel materials reported herein. A multifunctional macromer, methacrylated hyperbranched polyglycerol (HPG-MA) with an average of one acrylate unit per copolymer, was synthesized and copolymerized with N-isopropylacrylamide (NIPAAm), hydroxyethyl methacrylate-polylactide (HEMAPLA) and acrylic acid (AAc). The potential to fully exploit the copolymers by modification of the multiple HPG hydroxyl groups will not be discussed here. Instead, this report focuses on the thermoresponsive, biocompatible, and degradation properties of the material. Poly(NIPAAm-co-HEMAPLA-co-AAc-co-HPG-MA) displayed increasing lower critical solution temperatures (LCST) as the HPG content increased over a range of macromer ratios. For the copolymer with the maximum HPG incorporation (17%), the LCST was ~30 °C. In addition, this sample showed no toxicity when human uterine fibroid cells were co-cultured with the copolymer for up to 72 h. This copolymer lost approximately 92% of its mass after 17 hours at 37 °C. Thus, the reported biomaterials offer attractive properties for the design of drug delivery systems where orthogonally triggered mechanisms of therapeutic release in relatively short time periods would be attractive.