Disclosed herein are delivery systems including coated and uncoated yarns, yarn precursors, threads, fibers, and other substrates for the constant or near-constant release of active compounds, as well as methods for manufacturing such delivery systems. The yarns, yarn precursors, threads, fibers, and other substrates can include a cross-linked hydrophobic elastomer and an active compound. One or more coatings that are impermeable or substantially impermeable to the active compound may partially or fully occlude the yarn or substrate to control release rates of the active compound. The delivery systems may be used in a variety of applications, including the making of articles of clothing, textiles, and fabrics, and may be used in methods of treating various conditions and diseases.

At present, there is a great need for the development of new tumor pH-shiftable nanoparticles that are effective to reduce side effects, enhance active tumor focusing, improve the cellular uptake, and nuclear/cytoplasmic targeting of chemotherapy and gene therapeutic. Hence, we designed novel solid lipid nanoparticles (SLN) and liposomes (Lip) to deliver microRNA and antineoplastic agent, respectively. The designed SLN and liposomes incorporating microRNA and anticancer drugs in the core, which is surrounded by lipids modified with peptide T (a ligand plus a cell-penetrating peptide) and a nucleus-targeted sequence of peptide R as the inner shell. Moreover, coating a pH-responsive polymer (PGA-PEG) on the outer layer of Lip-TR (PGA-Lip-TR) and SLN-T (PGA-SLN-T) can protect the peptide T and R from degradation by peptidases during systemic circulation and enhance directing to the acidic tumor sites. Collectively, these pH-shiftable nanoparticles may provide a novel and potential strategy for anticancer therapy.

At present, there is a great need for the development of new tumor pH-shiftable nanoparticles that are effective to reduce side effects, enhance active tumor focusing, improve the cellular uptake, and nuclear/cytoplasmic targeting of chemotherapy and gene therapeutic. Hence, we designed novel solid lipid nanoparticles (SLN) and liposomes (Lip) to deliver microRNA and antineoplastic agent, respectively. The designed SLN and liposomes incorporating microRNA and anticancer drugs in the core, which is surrounded by lipids modified with peptide T (a ligand plus a cell-penetrating peptide) and a nucleus-targeted sequence of peptide R as the inner shell. Moreover, coating a pH-responsive polymer (PGA-PEG) on the outer layer of Lip-TR (PGA-Lip-TR) and SLN-T (PGA-SLN-T) can protect the peptide T and R from degradation by peptidases during systemic circulation and enhance directing to the acidic tumor sites. Collectively, these pH-shiftable nanoparticles may provide a novel and potential strategy for anticancer therapy.

Aspects of the present disclosure relate to compounds which have enhanced oral bioavailability. A transition metal complex includes a transition metal coordinated by a macrocycle comprising the pentaaza 15-membered macrocyclic ring corresponding to Formula A and two axial ligands having the formula OC(O)X.sub.1.

##STR00001## each of the two axial ligands has the formula OC(O)X.sub.1 wherein each X.sub.1 is independently substituted or unsubstituted phenyl or C(X.sub.2)(X.sub.3)(X.sub.4); each X.sub.2 is independently substituted or unsubstituted phenyl, or substituted or unsubstituted alkyl; each X.sub.3 is independently hydrogen, hydroxyl, alkyl, amino, X.sub.5C(O)R.sub.13 where X.sub.5 is NH or O, and R.sub.13 is C.sub.1-C.sub.18 alkyl, substituted or unsubstituted aryl or C.sub.1-C.sub.18 aralkyl, or OR.sub.14, where R.sub.14 is C.sub.1-C.sub.18 alkyl, substituted or unsubstituted aryl or C.sub.1-C.sub.18 aralkyl, or together with X.sub.4 is (O); and each X.sub.4 is independenly hydrogen or together with X.sub.3 is (O).

Aspects of the present disclosure relate to compounds which have enhanced oral bioavailability. A transition metal complex includes a transition metal coordinated by a macrocycle comprising the pentaaza 15-membered macrocyclic ring corresponding to Formula A and two axial ligands having the formula OC(O)X.sub.1.

##STR00001## each of the two axial ligands has the formula OC(O)X.sub.1 wherein each X.sub.1 is independently substituted or unsubstituted phenyl or C(X.sub.2)(X.sub.3)(X.sub.4); each X.sub.2 is independently substituted or unsubstituted phenyl, or substituted or unsubstituted alkyl; each X.sub.3 is independently hydrogen, hydroxyl, alkyl, amino, X.sub.5C(O)R.sub.13 where X.sub.5 is NH or O, and R.sub.13 is C.sub.1-C.sub.18 alkyl, substituted or unsubstituted aryl or C.sub.1-C.sub.18 aralkyl, or OR.sub.14, where R.sub.14 is C.sub.1-C.sub.18 alkyl, substituted or unsubstituted aryl or C.sub.1-C.sub.18 aralkyl, or together with X.sub.4 is (O); and each X.sub.4 is independenly hydrogen or together with X.sub.3 is (O).

The present invention relates to compositions and methods for treatment of cholangiocarcinoma and in particular to combination therapies comprising panobinostat compositions in combination with other cytotoxic agents, e.g. agents that potentiate the effects of panobinostat, for use in the treatment of cholangiocarcinoma. Pharmaceutical compositions comprising panobinostat and other cytotoxic agents are also provided.

The present invention relates to compositions and methods for treatment of cholangiocarcinoma and in particular to combination therapies comprising panobinostat compositions in combination with other cytotoxic agents, e.g. agents that potentiate the effects of panobinostat, for use in the treatment of cholangiocarcinoma. Pharmaceutical compositions comprising panobinostat and other cytotoxic agents are also provided.

A composition for use in the treatment and/or prevention of adverse side effects induced by an anti-cancer compound, said composition comprising an aqueous liquid extract, the aqueous liquid extract comprising Phycocyanin. The present invention also relates to the use of this aqueous liquid extract comprising Phycocyanin and optionally Spirulina polysaccharides, for the treatment and/or prevention of adverse side effects induced by an anti-cancer compound.

Indeed, Phycocyanin, thanks to its antioxidant effects, can reduce the undesirable side effects induced by an anti-cancer compound.

Drug delivery systems and wearable articles including the drug delivery systems are provided. The drug delivery systems may include a substrate coated with at least one polymer and at least one active compound. The substrate is operable to include yarns, yarn precursors, threads, filaments, fibers, and/or other suitable substrates. Methods for manufacturing drug delivery systems are also provided. The methods are operable to include disposing a solution including a monomer and an active compound on the substrate. The methods are also operable to include exposing the solution and the substrate to UV light to initiate polymerization of the solution.

Drug delivery systems and wearable articles including the drug delivery systems are provided. The drug delivery systems may include a substrate coated with at least one polymer and at least one active compound. The substrate is operable to include yarns, yarn precursors, threads, filaments, fibers, and/or other suitable substrates. Methods for manufacturing drug delivery systems are also provided. The methods are operable to include disposing a solution including a monomer and an active compound on the substrate. The methods are also operable to include exposing the solution and the substrate to UV light to initiate polymerization of the solution.