Formulations and Delivery Limitations of Nucleic‐Acid‐Based Therapies

Segura, Tatiana

doi:10.1002/9780470571224.pse321

Cited by 2 publications

(2 citation statements)

References 291 publications

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“…Despite all obstacles, there are encouraging reports describing the successful in vivo expression of genes after topical delivery of DNA loaded on cationic or PEGylated liposome as well as chitosan nanoparticles 105–107. Tissue growth, vaccination, anticancer treatment, and anti-inflammatory therapy can be achieved by gene transfer or regulation of gene expression 108,109. Principally, all skin diseases with a genetic basis could be treated by delivery of the missing or dysfunctional gene.…”

Section: Challenges For Carrier-based Dermatotherapiesmentioning

confidence: 99%

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Utilization of biodegradable polymeric materials as delivery agents in dermatology

Rancan

Blume-Peytavi

Vogt

2014

CCID

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Biodegradable polymeric materials are ideal carrier systems for biomedical applications. Features like controlled and sustained delivery, improved drug pharmacokinetics, reduced side effects and safe degradation make the use of these materials very attractive in a lot of medical fields, with dermatology included. A number of studies have shown that particle-based formulations can improve the skin penetration of topically applied drugs. However, for a successful translation of these promising results into a clinical application, a more rational approach is needed to take into account the different properties of diseased skin and the fate of these polymeric materials after topical application. In fact, each pathological skin condition poses different challenges and the way diseased skin interacts with polymeric carriers might be markedly different to that of healthy skin. In most inflammatory skin conditions, the skin’s barrier is impaired and the local immune system is activated. A better understanding of such mechanisms has the potential to improve the efficacy of carrier-based dermatotherapy. Such knowledge would allow the informed choice of the type of polymeric carrier depending on the skin condition to be treated, the type of drug to be loaded, and the desired release kinetics. Furthermore, a better control of polymer degradation and release properties in accordance with the skin environment would improve the safety and the selectivity of drug release. This review aims at summarizing the current knowledge on how polymeric delivery systems interact with healthy and diseased skin, giving an overview of the challenges that different pathological skin conditions pose to the development of safer and more specific dermatotherapies.

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Section: Challenges For Carrier-based Dermatotherapiesmentioning

confidence: 99%

“… 105 – 107 Tissue growth, vaccination, anticancer treatment, and anti-inflammatory therapy can be achieved by gene transfer or regulation of gene expression. 108 , 109 Principally, all skin diseases with a genetic basis could be treated by delivery of the missing or dysfunctional gene.…”

Section: Challenges For Carrier-based Dermatotherapiesmentioning

confidence: 99%

Utilization of biodegradable polymeric materials as delivery agents in dermatology

Rancan

Blume-Peytavi

Vogt

2014

CCID

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Poly[N-(2-aminoethyl)ethyleneimine] as a New Non-Viral Gene Delivery Carrier: The Effect of Two Protonatable Nitrogens in the Monomer Unit on Gene Delivery Efficiency

et al. 2014

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Purpose. The aim of this study was to investigate the in vitro gene delivery efficiency of poly[N-(2-aminoethyl)ethylene-imine](PAEEI), a polymer with a linear Polyethyleneimine (LPEI) backbone and with aminoethyl side groups that has two protonatable nitrogen atoms per monomer unit instead of one as in LPEI (an established gene delivery polymer). Method. PAEEI (Mn=4.5 kDa, Mw= 10 kDa) was synthesized by ring-opening polymerization of N-(2-(1’-aziridino)ethyl)formamide followed by hydrolysis of the amide groups. The buffering capacity of the resulting polymer was determined by acid-base titration and consequently the percentage of the protonated nitrogen atoms was calculated. Polyplexes were prepared separately in buffers with different ionic strength including Hepes buffered saline (150 mM NaCl) and Hepes buffered glucose (5% glucose) and their zeta-potential, hydrodynamic diameter and colloidal stability were measured. Transfection activity (and toxicity in Hela cells) of the polyplexes were done in HeLa, CHO and HEK293T cells. Cell incubations with polyplexes were done both in the presence and absence (HeLa cells) of serum. Results. PAEEEI showed two times more buffering capacity than LPEI. PAEEI-based Polyplexes had about the same size and zeta-potential as those of LPEI, with a higher colloidal stability in saline buffer in continuous particle size measurement. Their transfection activity was slightly higher than 22-kDa LPEI polyplexes whereas their toxicity profiles were similar in cell lines studied. The PAEEI polyplexes showed gene expression activity both in the presence and absence of serum. Conclusion. Paying attention to the fact that LPEI molecules with smaller sizes than 22 kDa show less transfection efficiency than LPEI 22, the effect of smaller size of PAEEI (10 kDa) on the gene delivery efficiency was compensated by its higher buffering capacity due to carrying more protonatable nitrogen per monomeric unit comparing with LPEI (22 kDa). Having slightly higher transfection efficiency and better colloidal stability than PEI-based systems, PAEEI is an attractive candidate for future in vivo gene delivery studies.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Formulations and Delivery Limitations of Nucleic‐Acid‐Based Therapies

Cited by 2 publications

References 291 publications

Utilization of biodegradable polymeric materials as delivery agents in dermatology

Utilization of biodegradable polymeric materials as delivery agents in dermatology

Poly[N-(2-aminoethyl)ethyleneimine] as a New Non-Viral Gene Delivery Carrier: The Effect of Two Protonatable Nitrogens in the Monomer Unit on Gene Delivery Efficiency

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