Cross-Linked Poly(cyclotriphosphazene-co-phloretin) Microspheres and Their Application for Controlled Drug Delivery

Mehmood, Sahid; Yu, Haipeng; Wang, Li; Uddin, Md Alim; Amin, Bilal Ul; Haq, Fazal; Fahad, Shah; Haroon, Muhammad

doi:10.1007/s13233-022-0066-0

Cited by 14 publications

(4 citation statements)

References 39 publications

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“…Recently, an innovative hydrogel containing polymeric nanocapsules loaded with phloretin has been developed, which enhanced skin penetration and adhesion, and was therefore used to treat skin cancer-related issues without showing any side effects [76]. Recently, cross-linked poly(cyclotriphosphazene-co-phloretin) microspheres have been developed and are being tested for their application for controlled drug delivery in the treatment of cancer [78].…”

Section: Nano Delivery Studies Of Phloretinmentioning

confidence: 99%

Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

et al. 2022

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Phloretin is a natural dihydrochalcone found in many fruits and vegetables, especially in apple tree leaves and the Manchurian apricots, exhibiting several therapeutic properties, such as antioxidant, antidiabetic, anti-inflammatory, and antitumor activities. In this review article, the diverse aspects of the anticancer potential of phloretin are addressed, presenting its antiproliferative, proapoptotic, antimetastatic, and antiangiogenic activities in many different preclinical cancer models. The fact that phloretin is a planar lipophilic polyphenol and, thus, a membrane-disrupting Pan-Assay Interference compound (PAIN) compromises the validity of the cell-based anticancer activities. Phloretin significantly reduces membrane dipole potential and, therefore, is expected to be able to activate a number of cellular signaling pathways in a non-specific way. In this way, the effects of this minor flavonoid on Bax and Bcl-2 proteins, caspases and MMPs, cytokines, and inflammatory enzymes are all analyzed in the current review. Moreover, besides the anticancer activities exerted by phloretin alone, its co-effects with conventional anticancer drugs are also under discussion. Therefore, this review presents a thorough overview of the preclinical anticancer potential of phloretin, allowing one to take the next steps in the development of novel drug candidates and move on to clinical trials.

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Section: Nano Delivery Studies Of Phloretinmentioning

confidence: 99%

Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

et al. 2022

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“…The hydrogen-bonding interaction between acriflavine molecules and quercetin nanospheres may also contribute to the steady release rate ( Scheme 10 ) [ 160 ]. Radical-containing microspheres based on a cyclophosphazene core and phloretin polymeric arms have been prepared by reaction with (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) and used as drug loading (camptothecin) while investigating the drug release at different pH levels: it was reported that 41% of camptothecin was released at a pH of 4.0 and 32.6% at a pH of 7.4 from microspheres after 350 h, respectively ( Scheme 10 ) [ 161 ].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Cyclo- and Polyphosphazenes for Biomedical Applications

et al. 2022

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Cyclic and polyphosphazenes are extremely interesting and versatile substrates characterized by the presence of -P=N- repeating units. The chlorine atoms on the P atoms in the starting materials can be easily substituted with a variety of organic substituents, thus giving rise to a huge number of new materials for industrial applications. Their properties can be designed considering the number of repetitive units and the nature of the substituent groups, opening up to a number of peculiar properties, including the ability to give rise to supramolecular arrangements. We focused our attention on the extensive scientific literature concerning their biomedical applications: as antimicrobial agents in drug delivery, as immunoadjuvants in tissue engineering, in innovative anticancer therapies, and treatments for cardiovascular diseases. The promising perspectives for their biomedical use rise from the opportunity to combine the benefits of the inorganic backbone and the wide variety of organic side groups that can lead to the formation of nanoparticles, polymersomes, or scaffolds for cell proliferation. In this review, some aspects of the preparation of phosphazene-based systems and their characterization, together with some of the most relevant chemical strategies to obtain biomaterials, have been described.

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“…[ 14 ] Cyclomatrix polyphosphazene is a type of highly crosslinked polymer formed through the direct precipitation polymerization of hexachlorocyclotriphosphonitrile (HCCP) and polyphenolic monomers via nucleophilic substitution reactions under environmentally friendly conditions. [ 15 ] Since Phloretin contains four hydroxyl groups, it is susceptible to nucleophilic substitution and covalent cross‐linking with HCCP to form microspheres. [ 15 ] These cyclomatrix polyphosphazene can be utilized as carriers for Phloretin, acting as prodrugs that encapsulate the compound.…”

Section: Introductionmentioning

confidence: 99%

“…[ 15 ] Since Phloretin contains four hydroxyl groups, it is susceptible to nucleophilic substitution and covalent cross‐linking with HCCP to form microspheres. [ 15 ] These cyclomatrix polyphosphazene can be utilized as carriers for Phloretin, acting as prodrugs that encapsulate the compound. Using such prodrug carriers enables the regulation of Phloretin release by adjusting the degradation of the polyphosphazene, thus addressing the issue of initial burst release.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial, Antioxidant, and Anti‐Inflammatory Nanoplatform for Effective Management of Infected Wounds

Su,

Chen,

Jing

et al. 2023

Adv Healthcare Materials

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Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti‐inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH‐sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro‐inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti‐inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.

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Cross-Linked Poly(cyclotriphosphazene-co-phloretin) Microspheres and Their Application for Controlled Drug Delivery

Cited by 14 publications

References 39 publications

Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

Phloretin, as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

Cyclo- and Polyphosphazenes for Biomedical Applications

Antimicrobial, Antioxidant, and Anti‐Inflammatory Nanoplatform for Effective Management of Infected Wounds

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