Poly(succinimide) nanoparticles as reservoirs for spontaneous and sustained synthesis of poly(aspartic acid) under physiological conditions: potential for vascular calcification therapy and oral drug delivery

Adelnia, Hossein; Blakey, Idriss; Little, Peter J.; Ta, Hang T.

doi:10.1039/d2tb01867e

Cited by 10 publications

(8 citation statements)

References 34 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PSI was synthesised using poly-condensation reactions of aspartic acid as described by Adelnia et al [34], Nakato et al [35] and Tomida et al [36]. Aspartic acid (21 g), H 3 PO 4 (1.5 ml) and sulfolane (75 ml) were separately poured into a 100 ml three-necked flask immersed in a 185 °C oil bath under nitrogen gas flow with 150 rpm over-head stirring.…”

Section: Synthesis Of Psimentioning

confidence: 99%

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method

Chen,

Moonshi,

Nguyen

et al. 2023

Nanotechnology

Self Cite

View full text Add to dashboard Cite

Currently, the treatment for acute disease encompasses the use of various biological drugs (BDs). However, the utilisation of BDs is limited due to its rapid clearance and non-specific accumulation in unwanted sites which results in a lack of therapeutic efficacy accompanied with adverse effects. While nanoparticles were considered a good candidate to resolve this problem, some available polymeric carriers for these BDs are mainly designed for long-term sustained release. Thus, there is a need to explore new polymeric carriers for diseases’ acute phase that requires sustained release of BDs in a short period such as thrombolysis and infec-tion. Poly(succinimide)-oleylamine (PSI-OA), a biocompatible polymer with tuneable dissolu-tion profile, represents a promising strategy to load BD for sustained release within a 48-hour period. In this work, we developed a two-step nanoprecipitation method to load the model protein (e.g. bovine serum albumin (BSA) and lipase) with PSI-OA. The characteristics of the nanoparticles were assessed based on various loading parameters, such as concentration, stir-ring rate, flow rate, volume ratios, dissolution, and the release of the protein. The optimised NPs displayed a size within 200 nm that is suitable for vasculature delivery to the target sites. These findings suggest that PSI-OA can be employed as a carrier for BDs for applications that require sustained release in a short period.

show abstract

Section: Synthesis Of Psimentioning

confidence: 99%

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method

Chen,

Moonshi,

Nguyen

et al. 2023

Nanotechnology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This can be explained by the insolubility of PSI in water. When PSI is exposed to water, its structure collapses instantaneously, and polymer precipitation is evenly dispersed and blended in NaAlg before this mixture forms a hydrogel with CaCl 2 crosslinking, leading to a rough surface [31]. This demonstrates that PSI was incorporated into the hydrogel.…”

Section: Synthesis and Characterization Of Alg-psimentioning

confidence: 99%

“…PSI nanoparticles (NPs) were shown to hydrolyze slowly under physiological pH 7.4 conditions while being stable under acidic conditions. The ability of NPs to be dissolved under neutral conditions while maintaining stability in acidic environments is a highly desirable property for oral delivery technologies [31]. Therefore, it is considered that PSI exhibits potential for the development of medication delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Development of Efficient Sodium Alginate/Polysuccinimide-Based Hydrogels as Biodegradable Acetaminophen Delivery Systems

Trinh,

Lim,

Lee

et al. 2023

Gels

View full text Add to dashboard Cite

Efficient drug delivery systems are essential for improving patient outcomes. Acetaminophen (AP), which is a kind of oral administration, is a commonly used pain reliever and fever reducer. However, oral administration carries various health risks, especially overdose and frequent use; for instance, AP is administered approximately 4 times per day. Therefore, the aim of this study is to develop an efficient delivery system for once-daily administration by combining sodium alginate and polysuccinimide (PSI) hydrogels to delay the release of analgesic AP. PSI is a biodegradable polymer that can be used safely and effectively in drug delivery systems because it is eliminated by hydrolysis in the intestine. The use of PSI also improves the mechanical properties of hydrogels and prolongs drug release. In this study, hydrogel characterizations such as mechanical properties, drug dissolution ability, and biodegradability were measured to evaluate the hydrolysis of PSI in the intestine. Based on the results, hydrogels could be designed to improve the structural mechanical properties and to allow the drug to be completely dissolved, and eliminated from the body through PSI hydrolysis in the intestines. In addition, the release profiles of AP in the hydrogels were evaluated, and the hydrogels provided continuous release of AP for 24 h. Our research suggests that sodium alginate/PSI hydrogels can potentially serve as biodegradable delivery systems for AP. These findings may have significant implications for developing efficient drug delivery systems for other classes of drugs.

show abstract

“…We recently showed that PASP could be spontaneously, inherently, and slowly synthesized in the physiological conditions from its precursor PSI. 25 In addition to its bioactivity, PSI, as a hydrophobic polymer, can also serve as a carrier of hydrophobic agents, providing a potential platform for the delivery of drugs that are clinically limited with drawbacks, such as low aqueous solubility and rapid metabolism/degradation. Due to the slow conversion to PASP, PSI NPs are expected to release their cargo in a sustained manner, consistent with their dissolution profile.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in our study we proposed using polysuccinimide (PSI), a precursor of PASP, instead of PASP to avoid potential side-effects associated with the direct administration of PASP. We recently showed that PASP could be spontaneously, inherently, and slowly synthesized in the physiological conditions from its precursor PSI …”

Section: Introductionmentioning

confidence: 99%

A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification

Adelnia,

Moonshi,

et al. 2023

ACS Nano

Self Cite

View full text Add to dashboard Cite

Although poly(aspartic acid) (PASP), a strong calcium chelating agent, may be potentially effective in inhibition of vascular calcification, its direct administration may lead to side effects. In this study, we employed polysuccinimide, a precursor of PASP, to prepare targeted polysuccinimide-based nanoparticles (PSI NPs) that not only acted as a prodrug but also functioned as a carrier of additional therapeutics to provide powerful synergistic vascular anticalcification effect. This paper shows that chemically modified PSI-NPs can serve as effective nanocarriers for loading of hydrophobic drugs, in addition to anticalcification and antireactive oxygen species (anti-ROS) activities. Curcumin (Cur), with high loading efficiency, was encapsulated into the NPs. The NPs were stable for 16 h in physiological conditions and then slowly dissolved/hydrolyzed to release the therapeutic PASP and the encapsulated drug. The drug release profile was found to be in good agreement with the NP dissolution profile such that complete release occurred after 48 h at physiological conditions. However, under acidic conditions, the NPs were stable, and Cur cumulative release reached only 30% after 1 week. Though highly effective in the prevention of calcium deposition, PSI NPs could not prevent the osteogenic trans-differentiation of vascular smooth muscle cells (VSMCs). The presence of Cur addressed this problem. It not only further reduced ROS level in macrophages but also prevented osteogenic differentiation of VSMCs in vitro. The NPs were examined in vivo in a rat model of vascular calcification induced by kidney failure through an adenine diet. The inclusion of Cur and PSI NPs combined the therapeutic effects of both. Cur-loaded NPs significantly reduced calcium deposition in the aorta without adversely affecting bone integrity or noticeable side effects/toxicity as examined by organ histological and serum biochemistry analyses.

show abstract

Poly(succinimide) nanoparticles as reservoirs for spontaneous and sustained synthesis of poly(aspartic acid) under physiological conditions: potential for vascular calcification therapy and oral drug delivery

Abstract: This paper describes the preparation of poly(succinimide) nanoparticles (PSI NPs) and investigates their properties and characteristics. Employing direct and inverse precipitation methods, stable PSI NPs with tunable size and narrow...

Cited by 10 publications

References 34 publications

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method

Development of Efficient Sodium Alginate/Polysuccinimide-Based Hydrogels as Biodegradable Acetaminophen Delivery Systems

A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification

Contact Info

Product

Resources

About