Preparation, characterization, and in vitro evaluation of amphiphilic peptide P12 and P12-DOX nanomicelles as antitumor drug carriers

Song, Ping; Du, Wuchen; Li, Wanzhen; Zhu, Liping; Zhang, Weiwei; Gao, Xinxing; Tao, Yugui; Ge, Fei

doi:10.1177/1847980420911519

Cited by 13 publications

(14 citation statements)

References 30 publications

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“…In this study, AS-AL-mPEG-PLGA was prepared by the dialysis method as described in the previous study (Song et al., 2020 ). Next, 10 mg of AL-mPEG-PLGA was precisely weighed and dissolved in 10 mL of distilled water.…”

Section: Methodsmentioning

confidence: 99%

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats

Xi¹,

Wang²,

et al. 2022

Drug Delivery

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Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (−23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10–200 μg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.

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Section: Methodsmentioning

confidence: 99%

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats

Xi¹,

Wang²,

et al. 2022

Drug Delivery

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“…46,47 The product was obtained in a 90% yield. 1 Synthesis of Glu(OtBu)-NCA. A reflux column and an argon (Ar) inlet and outlet were fitted to a dry evacuated two-neck flask containing Glu(OtBu) (10.0 g; 49.0 mmol).…”

Section: ■ Materials and Instrumentationmentioning

confidence: 99%

“…Recently, various smart drug carriers, including liposomes, micelles, nanotubes, dendrimers, and peptides, have been designed. Significant common characteristics of these carriers are their high targeting ability, high efficiency, biocompatibility, responsiveness to specific triggers in tumor microenvironments, and ability to control drug release . Micelles can be formed by the self-assembly of amphiphilic copolymers.…”

Section: Introductionmentioning

confidence: 99%

“…42 Incorporating RGD as a targeting agent on the surface of the amphiphilic arborescent polymers would improve the current work even further. We should also highlight that a high magnetic field (800 MHz) 1 H NMR spectroscopy was used for the RGD ratio determination. DOX is widely used in chemotherapy to treat many cancer types; 43 it was loaded by physical entrapment in the arborescent polypeptide unimolecular micelles to study the loading capacity of the system.…”

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confidence: 99%

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Hybrid Arborescent Polypeptide-Based Unimolecular Micelles: Synthesis, Characterization, and Drug Encapsulation

2022

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This paper reports novel hybrid arborescent polypeptides based on poly(γ-benzyl l-glutamate)-co-poly(γ-tert-butyl l-glutamate)-g-polysarcosine [P(BG-co-Glu(OtBu))-g-PSar]. The synthesis is launched by ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl l-glutamate (BG-NCA) and γ-tert-butyl l-glutamate (Glu(OtBu)-NCA) to synthesize a random copolymer P(BG-co-Glu(OtBu)) serving as a precursor for the arborescent system, followed by deprotection of the tert-butyl (tBu) groups to afford free COOH moieties serving as coupling sites. Two copolymerization reactions were carried out to afford the side chains. One type of side chain was a random copolymer P(BG-co-Glu(OtBu)), while the other type was a triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu). The peptide coupling reactions were conducted between the COOH moieties on the precursor and the terminus amine on the chain end of the P(BG-co-Glu(OtBu)) random copolymer or the PGlu(OtBu)-b-PBG-b-PGlu(OtBu) triblock copolymer to obtain G0 polymers. Afterward, hydrolyzing the tBu moieties of the G0 substrates yielded randomly functionalized G0 and end-functionalized G0. Randomly functionalized G0 was used as a substrate for the next generation G1 (randomly functionalized and end-functionalized G1 after deprotection) or coated with polysarcosine (PSar) to gain G0-g-PSar. The G0 substrate prepared with the triblock copolymer PGlu(OtBu)-b-PBG-b-PGlu(OtBu) was only grafted with PSar after deprotection, resulting in G0-eg-PSar. Depending on the functionality mode of the G1 substrate, the PSar coating yielded two different graft polymers, G1-g-PSar and G1-eg-PSar, for randomly functionalized and end-functionalized G1, respectively. The PSar hydrophilic shell was decorated with the sequence of (arginine, glycine, and aspartic acid) tripeptides (RGD) as a targeting ligand to improve the potentiality of the arborescent unimolecular micelles as drug carriers. Preparative size exclusion chromatography (SEC) was used to fractionate these complex macromolecular architectures. Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), Raman spectroscopy, and SEC were used for molecular characterization of all intermediate and final products and dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) for micellar characterization. A comparison between randomly grafted (g) and end-grafted (eg) unimolecular micelles demonstrates that the former has an undefined core–shell structure, unlike its end-grafted analog. In addition, this study has proved that decoration of the shell with RGD contributed to avoiding micelle aggregation but limited chemotherapy agent encapsulation. However, more than their naked analog, the sustained release was noticeable in decorated micelles. Doxorubicin was utilized as a chemotherapy model, and loading was achieved successfully by physical entrapment.

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“…Recently, the application of nanotechnology such as micelles, liposomes, nanoparticles, microemulsions, and nanoemulsions has attracted attention for improving oral absorption and bioavailability. 9 Microemulsions and nanoemulsions are emulsion-based delivery systems, having some unique properties that benefit their application in drug delivery including simplicity of preparation, and their ability to improve the physical stability of natural oils. 10 –14 Both systems have a small particle size (less than 200 nm) and have a lipophilic core and a hydrophilic shell; nevertheless, nanoemulsions are thermodynamically unstable systems but can be designed to be kinetically stable, whereas microemulsions are thermodynamically stable.…”

Section: Introductionmentioning

confidence: 99%

Formulation design and pharmacokinetic evaluation of docosahexaenoic acid containing self-nanoemulsifying drug delivery system for oral administration

Alhakamy

Aldawsari

Hosny

et al. 2020

Nanomaterials and Nanotechnology

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Docosahexaenoic acid is a omega-3-fatty acid which together with other long-chain omega-3-fatty acid known to have protective effect against various diseases including hypertension, myocardial infarction, Alzheimer disease, and cancers. Poor bioavailability owning to limited aqueous solubility limits its effective therapeutic delivery. Self-nanoemulsifying drug delivery systems are known to enhance the systemic absorption of poorly bioavailable lipophilic bioactive/therapeutics compounds. The purpose of this work was to investigate the potential of self-nanoemulsifying drug delivery systems produced by spontaneous nanoemulsification to enhance the oral bioavailability of docosahexaenoic acid. Initially, the screening of oil, surfactant, and cosurfactant was carried out by determining the miscibility and emulsifiability of the component with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems were prepared using Capryol 90, Tween 20, and polyethylene glycol 200 due to their excellent miscibility and emulsifiability with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems’ droplet size, size distribution, and zeta potential were found to be 111.5 ± 4.2 nm, 0.269 ± 0.05 nm, and −23.53 ± 2.9 mV, respectively. The in vitro drug release and ex vivo absorption studies showed better in vitro release and intestinal absorption as compared to docosahexaenoic acid aqueous dispersion. In vivo studies demonstrated a significant increase ( p < 0.001) in the oral bioavailability of docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems in comparison to a docosahexaenoic acid aqueous dispersion. This indicated the potential of self-nanoemulsifying drug delivery systems as an effective unit dosage form for the oral delivery of docosahexaenoic acid.

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Preparation, characterization, and in vitro evaluation of amphiphilic peptide P12 and P12-DOX nanomicelles as antitumor drug carriers

Cited by 13 publications

References 30 publications

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats

Hybrid Arborescent Polypeptide-Based Unimolecular Micelles: Synthesis, Characterization, and Drug Encapsulation

Formulation design and pharmacokinetic evaluation of docosahexaenoic acid containing self-nanoemulsifying drug delivery system for oral administration

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