One aspect of the present invention generally relates to methods of sealing a wound or tissue plane or filling a void splace. In a preferred embodiment, the wound is an ophthalmic, pleural or dural wound. In certain instances, the compositions used to seal the wound or tissue plane comprises a polyalkyleneimine. In a preferred embodiment, the polyalkyleneimine is polyethyleneimine. Treatment of the polyethyleneimine with a cross-linking reagent causes the polyethyleneimine polymers to polymerize forming a seal. In certain instances, the cross-linking reagent is a polyethylene glycol having reactive terminal groups. In certain instances, the reactive terminal groups are activated esters, such as N-hydroxy succinimide ester. In certain instances, the reactive terminal groups are isocyanates. In certain instances, the polyethyleneimine has a lysine, cysteine, isocysteine or other nucleophilic group attached to the periphery of the polymer. In certain instances, the polyethyleneimine is mixed with a second polymer, such as a polyethylene glycol containing nucleophilic groups. In certain instances, the compositions used to seal the wound or tissue plane are formed by reacting a polyalkyleneimine bearing electrophilic groups with a cross-linking reagent containing nucleophilic groups. In certain instances, the electrophilic groups on the polyalkyleneimine are activated esters, such as N-hydroxy succinimide ester. In certain instances, the compositions used to seal the wound or tissue plane are formed by reacting a polyalkyleneimine bearing photopolymerizable groups with ultraviolet or visible light. Compositions used to seal the wound which contain PEI or a derivative of PEI are found to adhere tightly to the tissue. Other aspects of the present invention relate to methods of filling a void of a patient or adhering tissue. In certain instances, the methods use a polyalkyleneimine. In a preferred embodiment, the polyalkyleneimine is polyethyleneimine. Another aspect of the present invention relates to a polymeric composition formed by exposing a polyalkyleneimine to an activated polyalkylene glycol. In certain instances, the composition is attached to mammalian tissue.

Disclosed herein are polymers containing repeating units of formula (I) or copolymers containing the repeating units of formula (I) and (II), where R.sup.1 to R.sup.12, m, n, p, q, x and y are as defined herein. The polymers and copolymers have an antimicrobial effect and may be used therapeutically or in formulations intended for use as detergents.

Disclosed herein are polymers containing repeating units of formula (I) or copolymers containing the repeating units of formula (I) and (II), where R.sup.1 to R.sup.12, m, n, p, q, x and y are as defined herein. The polymers and copolymers have an antimicrobial effect and may be used therapeutically or in formulations intended for use as detergents.

The disclosure is directed to methods of treating bile acid diarrhea by administering a CFTR chloride channel inhibitor (CFTR-CCI). The CFTR chloride channel inhibitor can be benzopyrimido-pyrrolo-oxazine-dione-CFTR-CCI (e.g., BPO-27), a PPQ-CFTR-CCI, a thiazolidinone-CFTR-CCI, or a glycine hydra-zide-CFTR-CCI.

The disclosure is directed to methods of treating bile acid diarrhea by administering a CFTR chloride channel inhibitor (CFTR-CCI). The CFTR chloride channel inhibitor can be benzopyrimido-pyrrolo-oxazine-dione-CFTR-CCI (e.g., BPO-27), a PPQ-CFTR-CCI, a thiazolidinone-CFTR-CCI, or a glycine hydra-zide-CFTR-CCI.

A polymer nanoparticle includes a polymer having repeating units of formula (I)

##STR00001##

wherein X, L.sup.1, and R.sup.1 are as defined herein. Methods of preparing the polymer nanoparticles and compositions comprising the nanoparticles are also disclosed. The polymers nanoparticles described herein are particularly useful for the treatment of bacterial biofilms.

A polymer nanoparticle includes a polymer having repeating units of formula (I)

##STR00001##

wherein X, L.sup.1, and R.sup.1 are as defined herein. Methods of preparing the polymer nanoparticles and compositions comprising the nanoparticles are also disclosed. The polymers nanoparticles described herein are particularly useful for the treatment of bacterial biofilms.

A polymer nanoparticle includes a polymer having repeating units of formula (I)

##STR00001##

wherein X, L.sup.1, and R.sup.1 are as defined herein. Methods of preparing the polymer nanoparticles and compositions comprising the nanoparticles are also disclosed. The polymers nanoparticles described herein are particularly useful for the treatment of bacterial biofilms.

Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.

Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.