Preparation and in vivo evaluation of cationic elastic liposomes comprising highly skin-permeable growth factors combined with hyaluronic acid for enhanced diabetic wound-healing therapy

Choi, Jeong Uk; Lee, Seong Wook; Pangeni, Rudra; Byun, Youngro; Yoon, In‐Soo; Park, Jin Woo

doi:10.1016/j.actbio.2017.04.034

Cited by 87 publications

(50 citation statements)

References 53 publications

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“…A treatment that combines several GFs may promote chronic wound repair. The most promising combination of GFs to enhance the mitogenic response of diabetic ulcer fibroblasts may include PDGF with IGF-I, bFGF, or EGF 26,27,61. Therefore, in this study, LMWP-fused EGF, IGF-I, PDGF-A, and bFGF in a concentration ratio of 50:50:1:1 were used to accelerate re-epithelialization and connective tissue formation, from the early stages of healing 26,27.…”

Section: Resultsmentioning

confidence: 99%

“…The most promising combination of GFs to enhance the mitogenic response of diabetic ulcer fibroblasts may include PDGF with IGF-I, bFGF, or EGF 26,27,61. Therefore, in this study, LMWP-fused EGF, IGF-I, PDGF-A, and bFGF in a concentration ratio of 50:50:1:1 were used to accelerate re-epithelialization and connective tissue formation, from the early stages of healing 26,27. IGF-I can reportedly act synergistically with EGF to promote the migration and proliferation of keratinocytes by upregulating the EGF receptor, resulting in an increase in the synthesis of fibronectin and other connective tissue molecules and stimulation of cell proliferation 62.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous studies, we designed rapid and enhanced skin-permeable EGF, IGF-I, PDGF-A, and basic fibroblast growth factor (bFGF) by genetically fusing a positively charged low-molecular-weight protamine (LMWP) to N-termini to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. These molecules had markedly increased in vitro skin infiltration, resulting in significantly accelerated recovery from acute and diabetic full-thickness wounds compared to native GFs 26,27…”

Section: Introductionmentioning

confidence: 99%

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<p>Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy</p>

Jee¹,

Pangeni²,

Jha³

et al. 2019

IJN

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Purpose We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site. Methods To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model. Results The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively. Conclusion LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy</p>

Jee¹,

Pangeni²,

Jha³

et al. 2019

IJN

Self Cite

View full text Add to dashboard Cite

show abstract

“…The presence of edge activator renders high flexibility of deformable liposomes and enables them to across the stratum corneum and reach the viable epidermis [46]. Uk Choi et al [47] conjugated low-molecular-weight protamine (LMWP) to the N-termini of EGF, PDGF-A and IGF-1, these molecules were subsequently complexed with hyaluronic acid and eventually incorporated into cationic deformable liposomes. The results showed that the cationic elastic liposomes containing the growth factor complex significantly accelerated the wound closure rate in the diabetic mouse model, with the maximal shrink of wound size by 58% compared with the native growth factor complex.…”

Section: Nano-drug Delivery System In Wound Treatment and Skin Regenementioning

confidence: 99%

Nano-drug delivery systems in wound treatment and skin regeneration

Wang¹,

Lu²,

Yu³

et al. 2019

J Nanobiotechnol

293

174

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Skin damages are defined as one of most common lesions people suffer from, some of wounds are notoriously difficult to eradicate such as chronic wounds and deep burns. Existing wound therapies have been proved to be inadequate and far from satisfactory. The cutting-edge nanotechnology offers an unprecedented opportunity to revolutionize and invent new therapies or boost the effectiveness of current medical treatments. In particular, the nano-drug delivery systems anchor bioactive molecules to applied area, sustain the drug release and explicitly enhance the therapeutic efficacies of drugs, thus making a fine figure in field relevant to skin regeneration. This review summarized and discussed the current nano-drug delivery systems holding pivotal potential for wound healing and skin regeneration, with a special emphasis on liposomes, polymeric nanoparticles, inorganic nanoparticles, lipid nanoparticles, nanofibrous structures and nanohydrogel.

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“…Also, they are a versatile drug delivery system when chemically modified with specific surface ligands [1,7]. There are several types of liposomes including, stimuli-triggered liposomes [8], nebulized liposomes [9], long circulating liposomes [10], elastic liposomes for topical [11], oral [12] and transdermal delivery [13] and covalent lipid-drug complexes. In the last decade, there is a promising approach to develop conventional liposomes through applying several advanced approaches such as modification of liposomes bilayers with certain polymer (like stealth liposomes); enhance their elasticity (like transferosomes) and recently employing targeting ligands.…”

Section: Liposomes and Drug Delivery System With Liposomesmentioning

confidence: 99%

Liposomes and PEGylated liposomes as drug delivery system

Mohamed

Alaaeldin

Hussein

et al. 2020

Journal of advanced Biomedical and Pharmaceutical Sciences

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Generally, it has been thought that PEG-conjugated nanocarriers are non-immunogenic. However, many reports have revealed that unexpected immune responses occur with such PEG-conjugated nanocarriers. The Most important one is the rapid clearance of PEGylated nanocarriers upon repeated administration which is called accelerated blood clearance phenomenon involving the production of antibodies against nanocarrier components, which reduces the safety and effectiveness of the encapsulated therapeutic agent. Such immunogenicity of PEGylated nanocarriers is a potential concern in the evaluation and clinic use of PEGylated therapeutics. Accordingly, screening of the immunogenicity of nanocarriers-based therapeutics is a prerequisite before their adoption into clinical settings to disclose any possible interactions with immune system. This review gives an overview of PEGylated liposomes, immunogenicity of PEG, explanation of accelerated blood clearance (ABC) phenomenon, its mechanism, various factors affecting it and side effects of PEGylated liposomes.

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Preparation and in vivo evaluation of cationic elastic liposomes comprising highly skin-permeable growth factors combined with hyaluronic acid for enhanced diabetic wound-healing therapy

Cited by 87 publications

References 53 publications

<p>Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy</p>

<p>Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy</p>

Nano-drug delivery systems in wound treatment and skin regeneration

Liposomes and PEGylated liposomes as drug delivery system

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