Injectable hydrogel enables local and sustained co-delivery to the brain: Two clinically approved biomolecules, cyclosporine and erythropoietin, accelerate functional recovery in rat model of stroke

Tuladhar, Anup; Obermeyer, Jaclyn M.; Payne, Samantha L.; Siu, Ricky; Zand, Sohrab; Morshead, Cindi M.; Shoichet, Molly S.

doi:10.1016/j.biomaterials.2020.119794

Cited by 52 publications

(39 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IP delivery was sufficient to transport protein to the CNS across the BBB. The system utilised the liver as a depot organ to reduce the frequency of drug administration [ 337 , 346 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

“…Shoichet and coworkers have reported the controlled release of proteins to address brain issues [ 335 , 346 , 347 , 348 ], such as stroke [ 335 , 346 , 348 ] and spinal cord injuries. [ 347 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

“…The hydrodynamic radius was increased by a factor of 1.5 and 1.2 after the addition of the first and second 5 kDa PEG, respectively. PEG modification was seen to reduce the rate of elimination of growth factor by an order of magnitude [ 346 ]. Tuladhar et al [ 346 ] reported the delivery of EPO (and cyclosporine) from a composite hydrogel comprising drug-loaded PLGA particles dispersed in HA and methylcellulose (MC) via surgery in a rat model of stroke [ 346 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

“…A 3-fold drug increase. as compared to systemic delivery, was reported with their formulation, since it was able to pass the BBB [ 346 ]. Cooke et al [ 335 ] designed a shear-thinning controlled release vehicle consisting of MC and HA to deliver epidermal growth factor (EGF) and PEG-EGF for the treatment of stroke (via surgery) [ 335 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

See 3 more Smart Citations

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

View full text Add to dashboard Cite

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

show abstract

“…IP delivery was sufficient to transport protein to the CNS across the BBB. The system utilised the liver as a depot organ to reduce the frequency of drug administration [ 337 , 346 ].…”

Section: Polypeptide Deliverymentioning

confidence: 99%

Section: Polypeptide Deliverymentioning

confidence: 99%

Section: Polypeptide Deliverymentioning

confidence: 99%

Section: Polypeptide Deliverymentioning

confidence: 99%

See 2 more Smart Citations

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The combination of hyaluronic acid + methyl cellulose (HAMC) has been used for the first time by Gupta et al (2006) and has been widely used in models of stroke, spinal cord injury, and retinal degeneration (Ho et al, 2019). One of the last published articles has been a study developed by Tuladhar et al (2020), where they have used this HAMC combination as a vehicle to release cyclosporine and erythropoietin, to promote functional recovery in stroke.…”

Section: Naturalmentioning

confidence: 99%

Neurorestoration Approach by Biomaterials in Ischemic Stroke

et al. 2020

View full text Add to dashboard Cite

BACKGROUND Stroke is one of the most important health problems worldwide. Ischemic stroke (IS) constitutes 85-90% of the casuistry among the types of stroke and is the leading cause of disability in people over 65 years of age worldwide (Ghuman and Modo, 2016). Due to the epidemiological importance and the big socioeconomic expenditure involved, it is priority advance in its prevention, control, and treatment (Kalaria et al., 2016; Benjamin et al., 2017). The ischemic injury is caused by an interruption of blood supply in one or more cerebral blood vessels triggering a set of dynamic processes that affect all brain cells and extracellular matrix (ECM) deteriorating the "glioneurovascular niche" (Boisserand et al., 2016). The pathophysiology of IS lies in the restriction or reduction of the supply of oxygen, glucose, and nutrients in the affected brain area. The ischemic cascade begins while there is arterial obstruction causing accidental cell death of core cells damaging tissue irreversibly. This process is accompanied by events of glutamate excitotoxicity, oxidative stress, and neuroinflammation, which affect the homeostatic functioning of the neurons in the affected tissue. The combination of all of them induces permanent brain lesions (Taylor et al., 2008; Thundyil and Lim, 2015; Thornton et al., 2017). However, there are regions near the nucleus or ischemic penumbra (IP) that have had access to a collateral blood circulation, being able to partially counteract the energy deficit (Fisher and Albers, 2013; Gavaret et al., 2019).

show abstract

Wielding the Double‐Edged Sword of Inflammation: Building Biomaterial‐Based Strategies for Immunomodulation in Ischemic Stroke Treatment

Khait

Shoichet

2021

Adv Funct Materials

Self Cite

View full text Add to dashboard Cite

Stroke is a leading cause of disability with no current treatment to regenerate lost brain tissue. Innovative preclinical and clinical trials have attempted to improve stroke recovery by promoting cell survival, downregulating astrogliosis and inflammation, and improving neurogenesis and angiogenesis; however, the complexity of stroke pathophysiology raises many challenges. Previous attempts to grossly inhibit the inflammatory reaction failed to improve stroke outcomes, prompting scientists to explore selective modulation rather than unbiased inhibition. Although experimental studies involving immunomodulation are successful, strategies have largely failed in the clinic. Some of these approaches are hindered by poor delivery efficiency or cell survival, challenges that could be at least partially overcome using biomaterials. Biomaterials may enhance immunomodulatory processes by improving drug and cell delivery to the injured tissue. Furthermore, the materials themselves can support healing and may be designed to act as immunomodulators, thereby contributing to tissue regeneration and endogenous repair processes. Described here are novel biomaterial-based strategies to modulate the immune response after ischemic stroke, with an emphasis on extracellular matrix mimetics and hydrogels for local delivery of drugs and cells. Finally, a future perspective is described, highlighting the potential of these therapies to achieve clinical translation and improve patients' functional repair.

show abstract

Injectable hydrogel enables local and sustained co-delivery to the brain: Two clinically approved biomolecules, cyclosporine and erythropoietin, accelerate functional recovery in rat model of stroke

Cited by 52 publications

References 66 publications

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Neurorestoration Approach by Biomaterials in Ischemic Stroke

Wielding the Double‐Edged Sword of Inflammation: Building Biomaterial‐Based Strategies for Immunomodulation in Ischemic Stroke Treatment

Contact Info

Product

Resources

About