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Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits.

ABSTRACT: Solid lipid nanoparticles (SLNs) are prospective carriers for oral delivery of poorly soluble drugs with low bioavailability. Therefore, the study aimed at developing carvedilol (CVD) in SLNs to control its release and enhance its bioavailability in the management of hypertension, and cardiac diseases. Box-Behnken design (BBD) was applied to optimize the variables affecting the quality of CVD-SLNs which prepared by homogenization-ultrasonication technique. The concentrations of Percirol (X1), Gelucire (X2), and stearylamine (X3) were chosen as the crucial independent variables. The dependent variables were estimated and analyzed by Statgraphics software to achieve the optimum characteristics of the developed SLNs. The optimized SLNs was evaluated in vitro and in vivo for pharmacokinetic parameters on male New Zealand white rabbits. The results of this study revealed that the CVD-SLNs have a colloidal size of 31.3 nm with zeta potential of 24.25 mV indicating good stability and 91.43% entrapment efficiency. The in vitro release of CVD from the SLNs was best fitted to Hixon-Crowell model that describes the release from the particles with uniform size. The in vivo pharmacokinetics results indicated the prolongation in the mean residence time of CVD to 23 h when delivered in SLNs and its oral bioavailability enhanced by more than 2-folds.

SUBMITTER: El-Say KM

PROVIDER: S-EPMC6117064 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits.

El-Say Khalid Mohamed KM Hosny Khaled Mohamed KM

PloS one 20180830 8

Solid lipid nanoparticles (SLNs) are prospective carriers for oral delivery of poorly soluble drugs with low bioavailability. Therefore, the study aimed at developing carvedilol (CVD) in SLNs to control its release and enhance its bioavailability in the management of hypertension, and cardiac diseases. Box-Behnken design (BBD) was applied to optimize the variables affecting the quality of CVD-SLNs which prepared by homogenization-ultrasonication technique. The concentrations of Percirol (X1), Ge ...[more]

PMID: 30161251

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Project description:Carvedilol (CRV) is an antihypertensive drug with both alpha and beta receptor blocking activity used to preclude angina and cardiac arrhythmias. To overcome the low, variable oral bioavailability of CRV, niosomal formulations were prepared and characterized: plain niosomes (without bile salts), bile salt-enriched niosomes (bilosomes containing various percentages of sodium cholate or sodium taurocholate), and charged niosomes (negative, containing dicetyl phosphate and positive, containing hexadecyl trimethyl ammonium bromide). All formulations were characterized in terms of encapsulation efficiency, size, zeta potential, release profile, stability, and morphology. Various formulations were administered orally to ten groups of Wistar rats (n=6 per group). The plasma levels of CRV were measured by a validated high-performance liquid chromatography (HPLC) method and pharmacokinetic properties of different formulations were characterized. Contribution of lymphatic transport to the oral bioavailability of niosomes was also investigated using a chylomicron flow-blocking approach. Of the bile salt-enriched vesicles examined, bilosomes containing 20% sodium cholate (F2) and 30% sodium taurocholate (F5) appeared to give the greatest enhancement of intestinal absorption. The relative bioavailability of F2 and F5 formulations to the suspension was estimated to be 1.84 and 1.64, respectively. With regard to charged niosomes, the peak plasma concentrations (Cmax) of CRV for positively (F7) and negatively charged formulations (F10) were approximately 2.3- and 1.7-fold higher than after a suspension. Bioavailability studies also revealed a significant increase in extent of drug absorption from charged vesicles. Tissue histology revealed no signs of inflammation or damage. The study proved that the type and concentration of bile salts as well as carrier surface charge had great influences on oral bioavailability of niosomes. Blocking the lymphatic absorption pathway significantly reduced oral bioavailability of CRV niosomes. Overall twofold enhancement in bioavailability in comparison with drug suspension confers the potential of niosomes as suitable carriers for improved oral delivery of CRV.

Project description:Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 106 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN®). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

Dataset Information

Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits.

Publications

Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits.

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