Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer

WANG, ZHIOXIONG; Itoh, Yoshiaki; Hosaka, Yoshifumi; Kobayashi, Ichiro; Nakano, Yoshihisa; Maeda, Isamu; Umeda, Fusako; Yamakawa, Junji; Kawase, Masaya; Yag, Kiyohito

doi:10.1016/s1389-1723(03)80059-2

Cited by 93 publications

(26 citation statements)

References 10 publications

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“…21 In the present study, we found that PEG-PAMAM could help DOX penetrate much deeper into bladder mucosa ( Figure 5). The actual mechanism of how PEG-PAMAM could enhance urothelial permeability is not yet fully understood.…”

Section: Discussionsupporting

confidence: 50%

“…As a drug carrier, PAMAM has showed its great ability to penetrate cell speroids, 19 oral mucosa, 20 and the skin. 21 Therefore, PAMAM is considered to be an applicable carrier for intravesical instillation, although it has not yet been explored. 5 This study was therefore designed to develop a drug delivery system on the basis of PAMAM and polyethylene glycol (PEG) for the enhancement of intravesical instillation.…”

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confidence: 99%

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Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

Qiu¹,

Cao²,

Lin³

et al. 2017

IJN

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Intravesical instillation of antitumor agents following transurethral resection of bladder tumors is the standard strategy for the treatment of superficial bladder cancers. However, the efficacy of current intravesical instillation is limited partly due to the poor permeability of the urothelium. We therefore aimed to develop a high-penetrating, target-releasing drug delivery system to improve the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier. Doxorubicin (DOX) was then encapsulated into PEG-PAMAM to generate DOX-loaded PEG-PAMAM nanoparticles (PEG-PAMAM-DOX). Our results indicated that the PEG-PAMAM was a stable nanocarrier with small size and great biosafety. The release of DOX from PEG-PAMAM-DOX was sluggish but could be effectively triggered in an acid microenvironment (pH =5.0). As a drug carrier, PEG-PAMAM could penetrate mice bladder urothelium effectively and increase the amount of DOX within the bladder wall after intravesical instillation. The antitumor effect of PEG-PAMAM-DOX was evaluated using an orthotopic bladder cancer model in mice. Compared to free DOX, PEG-PAMAM-DOX showed significantly improved efficacy of DOX for intravesical instillation with limited side effects. In conclusion, we successfully developed a PEG-PAMAM-based drug delivery system to enhance the antitumor effect of intravesical instillation.

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Section: Discussionsupporting

confidence: 50%

mentioning

confidence: 99%

Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

Qiu¹,

Cao²,

Lin³

et al. 2017

IJN

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“…Of the few reports available on the application of dendrimers for skin-mediated delivery of therapeutics, poly(amidoamine) (PAMAM) dendrimers have been among the most widely reported. Although PAMAM dendrimers have demonstrated potential in the delivery of a range of drugs such as riboflavin, tamsulosin, indomethacin, ketoprofen, diflunisal and 5-fluorouracil, toxicity issues remain an important concern and impediment in their broader use and applicability (Chauhan et al, 2003;Wang et al, 2003;Na et al, 2006;Parekh, 2007;Venuganti & Perumal, 2008;Filipowicz & Wolowiec, 2011).…”

Section: Introductionmentioning

confidence: 99%

Enhancement in deposition and permeation of 5-fluorouracil through human epidermis assisted by peptide dendrimers

et al. 2013

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Enhancing the deposition and permeation of 5-fluorouracil across human epidermis assisted by appropriately charged and well-defined peptide dendrimers was investigated. Peptide dendrimers with arginine as the terminal amino acid and having a range of terminal positive charges (4þ and 16 þ ) were synthesized by solid phase peptide synthesis. Various parameters including effect of peptide dendrimers on the solubility and partition coefficient of 5-FU, degradation of drug in skin as well as deposition and permeation of 5-FU in/through skin were studied. All the tested dendrimers increased the aqueous solubility and partition coefficient of 5-FU with each also significantly (p50.05) enhancing the deposition and permeation of 5-FU in/across human epidermis in a concentration-dependent manner. Of the three peptide dendrimers examined, R8 dendrimer (bearing 8 þ charge derived from four terminal arginines and MW of &1000 Da) showed greatest values for flux, Q 48 (cumulative amount of drug permeated at the end of 48 h) and amount of drug retained in human skin. Furthermore, this study also scrutinized and reports on the likely mechanisms by which peptide dendrimers act as transdermal permeation enhancers.

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“…They show promising results in the delivery of drugs such as tamsulosin [192], indomethacin [193], ketoprofen and diflunisal [194 ] and 5-fluorouracil [195]. The main problems with this kind of transdermal carrier are poor biodegradation and inherent cytotoxicity [158].…”

Section: Applications Of Nanocarrier Systems In Topical/transdermal Dmentioning

confidence: 99%

Nanocarrier Systems for Transdermal Drug Delivery

Escobar-Chávez¹,

Rodríguez-Cruz²,

Domínguez-Delgado³

et al. 2012

Recent Advances in Novel Drug Carrier Systems

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is an open discussion, in one hand, the nanotechnologist continue making new and more sophisticated nanocarriers and in the other hand, toxicologist continue evaluating possible damaging effects.Whatever it happens, nanotechnology is the new era and nanomedicine cannot be taking off. New nanocarriers will be created and the entire scientist working in nanomedicine bet for it to be the cure of diseases that in this moment are difficult to deal with [3] The application of preparations to the skin for medical purposes is as old as the history of medicine itself, with references to the use of ointments and salves found in the records of Babylonian and Egyptian medicine. The historical development of permeation research is well described by Hadgraft & Lane [4]. Over time, the skin has become an important route for drug delivery in which topical, regional or systemic effects are desired. Nevertheless, skin constitutes an excellent barrier and presents difficulties for the transdermal delivery of therapeutic agents, since few drugs possess the characteristics required to permeate across the stratum corneum in sufficient quantities to reach a therapeutic concentration in the blood. In order to enhance drug transdermal absorption different methodologies have been investigated developed and patented [5,6]. Improvement in physical permeationenhancement technologies has led to renewed interest in transdermal drug delivery. Some of these novel advanced transdermal permeation enhancement technologies include: iontophoresis, electroporation, ultrasound, microneedles to open up the skin and more recently the use of transdermal nanocarriers [3,[7][8][9][10].A number of excellent reviews that have been published contain detailed discussions concerning many aspects of transdermal nanocarriers [11][12][13][14][15][16][17]. The present chapter shows an updated overview of the use of submicron particles and other nanostructures in the pharmaceutical field, specifically in the area of topical and transdermal drugs. This focus is justified due to the magnitude of the experimental data available with the use of these nanocarriers. The development of submicron particles and other nanostructures in the pharmaceutical and cosmetic fields has been emerged in the last decades for designing best formulations for application through the skin [18][19][20][21]. The skinThe skin is the largest organ of the body [22][23][24], accounting for more than 10% of body mass, and the one that enables the body to interact more intimately with its environment. Essentially, the skin consists of four layers: The SC, that is the outer layer of the skin (nonviable epidermis), and forms the rate-controlling barrier for diffusion for almost all compounds. It is composed of dead flattened, keratin-rich cells, the corneocytes. These dense cells are surrounded by a complex mixture of intercellular lipids, namely, ceramides, free fatty acids, cholesterol, and cholesterol sulphate. Their most important feature is that they are structured as ordered bilayer arrays [25]...

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Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer

Cited by 93 publications

References 10 publications

Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

Enhancement in deposition and permeation of 5-fluorouracil through human epidermis assisted by peptide dendrimers

Nanocarrier Systems for Transdermal Drug Delivery

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