Polyglutamic Acid Functionalization of Chitosan Nanoparticles Enhances the Therapeutic Efficacy of Insulin Following Oral Administration

Urimi, Dileep; Agrawal, Ashish Kumar; Kushwah, Varun

doi:10.1208/s12249-019-1330-2

Cited by 32 publications

(12 citation statements)

References 30 publications

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“…Further improvement of SC-514 drug entrapment by conjugation during nanoparticle formulation can be considered advantageous in reduction of multidrug resistance in prostate cancer. This is important because prolonged drug release has been shown to reduce drug resistance in cancer treatment [114,115]. The goal of this study was to investigate SC-514 drug release from nanoparticle formulations that has the potential to reduce multidrug resistance by sustained release of SC-514 drug from the PLGA nanoparticle formulations.…”

Section: Resultsmentioning

confidence: 99%

“…The use of Nano encapsulation of SC-514 will improve the chance to target the prostate cancer cells and not harm normal prostate cells because targeted drug delivery of nanoparticles decorated with sitespecific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells [115]. SC-514 was internalized into the PLGA nanoparticles by endocytosis which may be released via endosome escape delivering the encapsulated SC-514 drug to the cytosol of the cells.…”

Section: Citationmentioning

confidence: 99%

“…However, the major limitation of this antibody-conjugated formulation such as SC-514-PLGA-NF-κBAb is the saturation of cell surface target protein (antigen). Once the surface antigen proteins are saturated, the formulation would not be able to target the neoplastic cells only and prolong presence without its distribution in neoplastic cells, which may affect normal prostate cells [115]. in-vivo studies.…”

Section: Citationmentioning

confidence: 99%

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Drug Release Studies of SC-514 PLGA Nanoparticles

Oloruntobi

Bowers

Bentley

et al. 2021

PVPE

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A major problem associated with prostate cancer treatment is the development of drug resistance. The development of drug resistance often leads to prostate cancer metastasis and prostate cancer-targeted drug delivery systems can be utilized to address this problem. Traditional drug delivery systems have many challenges, including the inability to control the drug release rate, target site inaccuracy, susceptibility to the microenvironment, poor drug solubility, and cytotoxicity of chemotherapeutics to non-malignant cells. As a result, there is an urgent need to formulate and functionalize a drug delivery system that better controls drug release. This study was designed to quantify the release of SC-514 from SC-514 Polylactic-Co-Glycolic Acid (PLGA) nanoparticles and conjugate SC-514-PLGA coated nanoparticles with the NF- κβ antibody, as well as fats. This study further explored new methods to quantify the release of SC-514 drug from the SC-514-PLGA coated nanoparticles after utilizing Liquid Chromatography–Mass Spectrometry (LC-MS) as the standard method to quantify SC-514 drug released. After quantification was completed, cell viability studies indicated that the ligand conjugated nanoparticles demonstrated a considerable ability to reduce tumor growth and SC-514 drug toxicity in the PC-3 cell line. The prepared drug delivery systems also possessed a significantly lower toxicity (P<0.05), bettered controlled-release behaviors in prostate cancer, and increased the solubility of SC-514 in comparison to free SC-514. SC-514 released from SC-514-PLGA, SC-514-PLGA-NF- κβAb, and SC-514-PLGA-Fat nanoparticles, significantly inhibited tumor growth when compared to that of free SC-514. The anti-cancer therapeutic effects of SC-514 were improved through the encapsulation of SC-514 with a PLGA polymer. The functionalized SC-514-PLGA nanoparticles can further control burst release. The new methods utilized in this study for quantifying drug release, may prove to be as effective as the current standard methods, such as LC/MS.

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Section: Resultsmentioning

confidence: 99%

Section: Citationmentioning

confidence: 99%

Section: Citationmentioning

confidence: 99%

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Drug Release Studies of SC-514 PLGA Nanoparticles

Oloruntobi

Bowers

Bentley

et al. 2021

PVPE

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“…Polymeric NPs were able to resist harsh gastric conditions, while the PGA coating increased intestinal uptake of the NPs via calcium-sensing receptors and amino acid transporters. Furthermore, in vivo assessment in Sprague-Dawley rats showed that CS-PGA NPs produced an increase in cumulative hypoglycemia 1.7 times greater than standard subcutaneous insulin administration, likely owing to a sustained release of insulin that was more similar to the physiological pattern [149].…”

Section: Major Biomedical Applications Of Model Bacterial Biopolymers 41 Drug Delivery Systemsmentioning

confidence: 99%

From Residues to Added-Value Bacterial Biopolymers as Nanomaterials for Biomedical Applications

et al. 2021

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Bacterial biopolymers are naturally occurring materials comprising a wide range of molecules with diverse chemical structures that can be produced from renewable sources following the principles of the circular economy. Over the last decades, they have gained substantial interest in the biomedical field as drug nanocarriers, implantable material coatings, and tissue-regeneration scaffolds or membranes due to their inherent biocompatibility, biodegradability into nonhazardous disintegration products, and their mechanical properties, which are similar to those of human tissues. The present review focuses upon three technologically advanced bacterial biopolymers, namely, bacterial cellulose (BC), polyhydroxyalkanoates (PHA), and γ-polyglutamic acid (PGA), as models of different carbon-backbone structures (polysaccharides, polyesters, and polyamides) produced by bacteria that are suitable for biomedical applications in nanoscale systems. This selection models evidence of the wide versatility of microorganisms to generate biopolymers by diverse metabolic strategies. We highlight the suitability for applied sustainable bioprocesses for the production of BC, PHA, and PGA based on renewable carbon sources and the singularity of each process driven by bacterial machinery. The inherent properties of each polymer can be fine-tuned by means of chemical and biotechnological approaches, such as metabolic engineering and peptide functionalization, to further expand their structural diversity and their applicability as nanomaterials in biomedicine.

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“…The smart polymer shielded PEI (MW=125,000)/DNA by forming ternary polyplex that aids electrostatic interactions between negatively charged cancer cells and positive polyplexes, leading to high cell uptake [62]. PLGA functionalization of chitosan NPs using poly(sodium 4-styrenesulfonate) as a cross-linking agent enhanced the therapeutic efficacy of insulin following oral administration [190]. The PLGA functionalization improved the oral uptake through calcium-sensing receptors and AA transporters present in intestinal epithelium.…”

Section: Types Of Ph-responsive Polypeptidesmentioning

confidence: 99%

pH-Responsive Polypeptide-Based Smart Nano-Carriers for Theranostic Applications

et al. 2019

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Smart nano-carriers have attained great significance in the biomedical field due to their versatile and interesting designs with different functionalities. The initial stages of the development of nanocarriers mainly focused on the guest loading efficiency, biocompatibility of the host and the circulation time. Later the requirements of less side effects with more efficacy arose by attributing targetability and stimuli-responsive characteristics to nano-carriers along with their bio- compatibility. Researchers are utilizing many stimuli-responsive polymers for the better release of the guest molecules at the targeted sites. Among these, pH-triggered release achieves increasing importance because of the pH variation in different organ and cancer cells of acidic pH. This specific feature is utilized to release the guest molecules more precisely in the targeted site by designing polymers having specific functionality with the pH dependent morphology change characteristics. In this review, we mainly concert on the pH-responsive polypeptides and some interesting nano-carrier designs for the effective theranostic applications. Also, emphasis is made on pharmaceutical application of the different nano-carriers with respect to the organ, tissue and cellular level pH environment.

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Polyglutamic Acid Functionalization of Chitosan Nanoparticles Enhances the Therapeutic Efficacy of Insulin Following Oral Administration

Cited by 32 publications

References 30 publications

Drug Release Studies of SC-514 PLGA Nanoparticles

Drug Release Studies of SC-514 PLGA Nanoparticles

From Residues to Added-Value Bacterial Biopolymers as Nanomaterials for Biomedical Applications

pH-Responsive Polypeptide-Based Smart Nano-Carriers for Theranostic Applications

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