Controlled release of injectable liposomal<i>in situ</i>gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits

Hassan, Ali; Hosny, Khaled M.; Murshid, Zuahir A.; Alhadlaq, Adel; Yamani, A.; Naguib, Ghada Hussein; Alkhalidi, Hala M.; Afify, Ahmed R.

doi:10.3109/08982104.2015.1060612

Cited by 12 publications

(17 citation statements)

References 37 publications

(36 reference statements)

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“…BMP target genes include a growing number of osteoblast-determining transcription factors such as Dlx5 , Runx2 and Osterix [ 12 , 13 ]. More importantly, the efficacy of BMPs in bone regeneration is well known in both animal models and clinical applications such as bone fracture healing [ 14 ], alveolar cleft defects [ 15 ], spinal fusion [ 16 ] and craniofacial bone defects [ 17 , 18 ]. As a result, BMP-2 and BMP-7 have been approved for medical use in specific osteoinductive applications.…”

Section: Introductionmentioning

confidence: 99%

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

et al. 2017

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Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

et al. 2017

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“…All the statistical analyses were carried out with GraphPad Prism Version 5.0 software. The integration of growth factors (GFs) in controlled release systems is a useful and much-explored method to improve their efficacy in vivo [28][29][30][31][32]. However, it is assumed that inducing the repair of complex tissues, such as cartilage, might only be possible through the orchestrated co-delivery of two or more GFs.…”

Section: Discussionmentioning

confidence: 99%

New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation

Crecente‐Campo

Borrajo

Vidal

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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“…Finally, the dried thin layer was reconstituted with PBS (phosphate buffer) with pH of 7.4 under continuous stirring for 60 min. The vesicles formed were allowed to swell at room temperature for 2-3 h [27,28]. The multilamellar vesicles were sonicated by Digital Sonifier (St Louis, MO, USA) for 15-20 min to lessen the vesicles' size and subsequently stored at 4 °C until further study.…”

Section: Preparation Of Amphotericin B Nanotransferosomes (Amp-nt)mentioning

confidence: 99%

“…The prepared formulation was added to a Petri dish. Freeze-dried, then the required quantity of acetonitrile was added and mixed vigorously to the dried sample [27]. The resulting dispersion was then centrifuged for 1 h at 10,000 rpm.…”

Section: Entrapment Efficacy (Ee)%mentioning

confidence: 99%

Nasal Gel Loaded with Amphotericin Nanotransferosomes as Antifungal Treatment for Fungal Sinusitis

Hosny

Alhakamy

2020

Pharmaceutics

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On the basis of fungal involvement, rhinosinusitis is categorized into allergic, mycetoma, chronic, and acute invasive types. The aim of the current study was to evaluate the efficacy of an amphotericin gel in situ loaded with nanotransferosomes against Aspergillus flavus, which causes allergic rhinosinusitis. A Box–Behnken design was utilized to study the interaction among the nanotransferosomes and optimize independent variables in formulating them, in order to match the prerequisites of selected responses. The optimal formulation was determined to be 300 mg/mL soybean lecithin, 200 mg/mL amphotericin B (AMP), and 150 mg/mL clove oil, resulting in a particle size of 155.09 nm, 84.30% entrapment efficacy (EE), inhibition zone of 16.0 mm, and 0.1197 mmol serum creatinine. The optimized batch was further prepared into an in situ gel and evaluated for various parameters. The optimized formulation released 79.25% AMP and enhanced permeation through the nasal membrane, while the other formulations did not achieve complete absorption. According to in vivo tests using rabbits as animal models, the optimized AMP-nanotransferosomal formulations (NT) in in situ gel result in a non-significant difference among the various kidney function parameters. In conclusion, nasal in situ gel loaded with AMP-clove oil nanotreansfersomes can act as a promising novel carrier that enhances antifungal activity and decreases AMP nephrotoxicity.

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Controlled release of injectable liposomalin situgel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits

Abstract: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.

Cited by 12 publications

References 37 publications

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation

Nasal Gel Loaded with Amphotericin Nanotransferosomes as Antifungal Treatment for Fungal Sinusitis

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