Temperature-responsive silk-elastinlike protein polymer enhancement of intravesical drug delivery of a therapeutic glycosaminoglycan for treatment of interstitial cystitis/painful bladder syndrome
“…Another emerging class of therapeutic GAGs involves semi-synthetic GAG-ethers (SAGE) offering both mucosal restoration and potent analgesic and anti-inflammatory effects. For example, SAGE GM-0111 was tested by several groups demonstrating attenuation of inflammation [ 43 , 44 , 45 ]. These novel GAGs offer improved protection of the damaged urothelium, but still encounter many limitations, such as poor urothelial binding and consequent fast clearance with micturition.…”
Section: Resultsmentioning
confidence: 99%
“…These novel GAGs offer improved protection of the damaged urothelium, but still encounter many limitations, such as poor urothelial binding and consequent fast clearance with micturition. The synthetic polymer drug delivery systems offer a better accumulation of GAGs, but can potentially weaken normal bladder function by reducing bladder capacity or causing bladder outflow obstruction (BOO) [ 43 ].…”
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.
“…Another emerging class of therapeutic GAGs involves semi-synthetic GAG-ethers (SAGE) offering both mucosal restoration and potent analgesic and anti-inflammatory effects. For example, SAGE GM-0111 was tested by several groups demonstrating attenuation of inflammation [ 43 , 44 , 45 ]. These novel GAGs offer improved protection of the damaged urothelium, but still encounter many limitations, such as poor urothelial binding and consequent fast clearance with micturition.…”
Section: Resultsmentioning
confidence: 99%
“…These novel GAGs offer improved protection of the damaged urothelium, but still encounter many limitations, such as poor urothelial binding and consequent fast clearance with micturition. The synthetic polymer drug delivery systems offer a better accumulation of GAGs, but can potentially weaken normal bladder function by reducing bladder capacity or causing bladder outflow obstruction (BOO) [ 43 ].…”
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.
“…The Ghandehari group synthesized positively charged SELP hydrogels that could electrostatically interact with an anionic polysaccharide —semisynthetic glycosaminoglycan ether (SAGE)— that is an anti-inflammatory drug for mucosa restoration. Unfortunately when SAGE is administered, it does not achieve a high enough therapeutic concentration due to its insufficiently long residence time [ 409 , 410 ]. To solve this problem for treatment of radiation-induced proctitis (RIP), the Ghandehari group designed an in situ gelling enema ( Fig.…”
Section: Applications In Drug Deliverymentioning
confidence: 99%
“…The Ghanedhari group further adapted the SELP platform for the sustained release of intravesically delivered SAGE for treatment of interstitial cystitis (IC) model. They found that employing a softer SELP with a slower gelation time could provide an analgesic effect for 24 h without exacerbating the discomfort associated with IC, whereas stiffer gels could reduce the capacity of or obstruct the bladder [ 409 ]. Fig.…”
Engineering protein and peptide-based materials for drug delivery applications has gained momentum due to their biochemical and biophysical properties over synthetic materials, including biocompatibility, ease of synthesis and purification, tunability, scalability, and lack of toxicity. These biomolecules have been used to develop a host of drug delivery platforms, such as peptide- and protein-drug conjugates, injectable particles, and drug depots to deliver small molecule drugs, therapeutic proteins, and nucleic acids. In this review, we discuss progress in engineering the architecture and biological functions of peptide-based biomaterials —naturally derived, chemically synthesized and recombinant— with a focus on the molecular features that modulate their structure-function relationships for drug delivery.
“…SELP hydrogels have been used as prolonged drug delivery systems for interstitial cystitis to repair the bladder mucosa, [ 69 ] as well as a treatment to reduce intraocular pressure to prevent glaucoma; [ 70 ] however, they are most commonly used in cancer therapies. [ 71 ] For example, Cappello, Ghandehari, and co‐workers have extensively studied SELPs for intratumoral, matrix‐mediated delivery of adenoviruses to improve thymidine kinase enzyme prodrug therapy in head and neck squamous cell carcinoma.…”
Elastin‐like polypeptides (ELPs) are thermally responsive biopolymers that consist of a repeated amino acid motif derived from human tropoelastin. These peptides exhibit temperature‐dependent phase behavior that can be harnessed to produce stimuli‐responsive biomaterials, such as nanoparticles or injectable drug delivery depots. As ELPs are genetically encoded, the properties of ELP‐based biomaterials can be controlled with a precision that is unattainable with synthetic polymers. Unique ELP architectures, such as spherical or rod‐like micelles or injectable coacervates, can be designed by manipulating the ELP amino acid sequence and length. ELPs can be loaded with drugs to create controlled, intelligent drug delivery systems. ELPs are biodegradable, nonimmunogenic, and tolerant of therapeutic additives. These qualities make ELPs exquisitely well‐suited to address current challenges in drug delivery and have spurred the development of ELP‐based therapeutics to treat diseases—such as cancer and diabetes—and to promote wound healing. This review focuses on the use of ELPs in drug delivery systems.
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