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- 저자 : Emirhan Nemutlu (검색결과 2 건)
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Electrospun Nanofibers for Dual and Local Delivery of Neuroprotective Drugs
Mohammad Karim Haidar,Selin Seda Timur,Gülen Melike Demirbolat,Emirhan Nemutlu,R. Neslihan Gürsoy,Kezban Ulubayram,Levent Öner,Hakan Eroğlu 한국섬유공학회 2021 Fibers and polymers Vol.22 No.2
Drug delivery for neuroprotection/neuroregeneration after traumatic peripheral nerve injuries still remains achallenge. For this purpose, we formulated composite nanofiber formulation for the dual local delivery of alpha lipoic acid(ALA) and atorvastatin (ATR) to enhance regeneration process after peripheral nerve injury. The initial stage involvedencapsulation of ATR into nanosprayed chitosan (CH) nanoparticles after which the CH nanoparticles were embedded intopoly(lactic-co-glycolic acid) (PLGA) nanofibers containing freely dispersed ALA within the fiber structure. Morphologyinvestigations revealed that smooth and randomly aligned nanofibers with mean diameter of 340±69 nm were formed. Encapsulation efficiency for ALA and ATR were calculated as 92.76±3.53 % and 89.27±5.053 %, respectively. DifferentialScanning Calorimetry and FT-IR analysis confirmed successful encapsulation of ALA and ATR into the compositenanofibers; however, XRD results indicated surface localization of ALA within the structure. Porosity and pore volume of thenanofibers increased in accordance with increase in density of the electrospunned solution. Similarly, mechanical strength ofthe nanofibers was found to increase significantly following the incorporation of ALA and ATR with respect to the unloadednanofibers (p<0.05). Dual release of ALA and ATR in different fashions was confirmed by in-vitro release test of thenanofibers. For ALA, an immediate release percentage of 83.90 % within the first hour was observed. On the other hand,ATR exhibited a three-stage release profile which begins with a relatively lower initial release (22.07 %) in comparison toALA followed by an increasing release (82.439 %) up to 150 h. According to cell viability results, blank and loadedformulations were found to have no cytotoxic effect on both L-929 and B35 cell lines after incubation for up to 48 h. Basedon this, composite PLGA nanofibers could be classified as suitable candidates for long-term and local delivery ofneuroprotective drugs in peripheral nerve injury.
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Erdoğar Nazlı,Akkın Safiye,Nielsen Thorbjorn T.,Özçelebi Esin,Erdoğdu Batuhan,Nemutlu Emirhan,İskit Alper B.,Bilensoy Erem 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.3
Purpose Aprepitant (APRT), a selective neurokinin 1 antagonist, is clinically used in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. The low solubility of APRT, which limits its oral bioavailability, is overcome by nanonization. This study aimed to design and evaluate novel in vitro and in vivo chitosan (CS)–polyethylene glycol (PEG)-coated cyclodextrin (CD) nanoparticles and nanocapsules to enhance the solubility and oral bioavailability of APRT. Methods A novel amphiphilic CD derivative with alkyl chains of 9 carbons (ACD-C9) was synthesized to form nanoparticles and nanocapsules by using nanoprecipitation. The nanocarriers were coated with the CS–PEG conjugate to increase their biological interaction with cell membranes via the positive charge and penetration-enhancer properties of CS. The nanosystems were evaluated for particle size, surface charge, drug loading, imaging, release, cell culture, and oral bioavailability in an animal model. Results The CS–PEG-coated nanosystems had particle size of 400–550 nm, a narrow polydispersity index, positive zeta potential, and favorable drug loading (55 and 93% for nanoparticles and nanocapsules, respectively). Sustained release was observed within 24 h. Blank nanoparticles and nanocapsules were non-cytotoxic against the L929 cell line. The intestinal permeability of the nanocarriers was 2–threefold (2-3 fold) higher than that of the drug solution, and the nanocapsules afforded the highest APRT permeability through Caco-2 cells. Oral bioavailability studies in rats revealed comparable degree of drug absorption between nanocapsules and commercial APRT products. Conclusion Oral ACD-C9 nanocapsules have the potential for the treatment of chemotherapy-induced nausea and vomiting.
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