Brain-targeted delivery of Valsartan using solid lipid nanoparticles labeled with Rhodamine B; a promising technique for mitigating the negative effects of stroke.
Shereen A SabryAmal M Abd El RazekMohamed NabilShaimaa M KhedrHanan Mohammed El-NahasNoura G EissaPublished in: Drug delivery (2023)
The brain is a vital organ that is protected from the general circulation and is distinguished by the presence of a relatively impermeable blood brain barrier (BBB). Blood brain barrier prevents the entry of foreign molecules. The current research aims to transport valsartan (Val) across BBB utilizing solid lipid nanoparticles (SLNs) approach to mitigate the adverse effects of stroke. Using a 3 2 -factorial design, we could investigate and optimize the effect of several variables in order to improve brain permeability of valsartan in a target-specific and sustained-release manner, which led to alleviation of ischemia-induced brain damage. The impact of each of the following independent variables was investigated: lipid concentration (% w/v), surfactant concentration (% w/v), and homogenization speed (RPM) on particle size, zeta potential (ZP), entrapment efficiency (EE) %, and cumulative drug release percentage (CDR) %. TEM images revealed a spherical form of the optimized nanoparticles, with particle size (215.76 ± 7.63 nm), PDI (0.311 ± 0.02), ZP (-15.26 ± 0.58 mV), EE (59.45 ± 0.88%), and CDR (87.59 ± 1.67%) for 72 hours. SLNs formulations showed sustained drug release, which could effectively reduce the dose frequency and improve patient compliance. DSC and X-ray emphasize that Val was encapsulated in the amorphous form. The in-vivo results revealed that the optimized formula successfully delivered Val to the brain through intranasal rout as compared to a pure Val solution and evidenced by the photon imaging and florescence intensity quantification. In a conclusion, the optimized SLN formula (F9) could be a promising therapy for delivering Val to brain, alleviating the negative consequences associated with stroke.
Keyphrases
- blood brain barrier
- cerebral ischemia
- drug release
- white matter
- resting state
- subarachnoid hemorrhage
- atrial fibrillation
- high resolution
- drug delivery
- brain injury
- fatty acid
- emergency department
- early stage
- computed tomography
- photodynamic therapy
- machine learning
- multiple sclerosis
- living cells
- endothelial cells
- preterm infants
- convolutional neural network
- magnetic resonance
- mass spectrometry
- high intensity
- optical coherence tomography
- drug induced
- contrast enhanced