Lisinopril loaded solid lipid nanoparticles; evaluation of the effect of chitosan coating on their invitro characteristics

Lisinopril belongs to a family of anti-hypertensive drugs named as angiotensin converting enzyme inhibitors (ACE inhibitors). This drug is used as hypertension-related disorders such as systemic hypertension and glaucoma via multiple extra-vascular administration routes. The bioavailability of lisinopril is poor and restricted to maximum 25% and thus many studies are conducted to increase its bioavailability. Application of nanotechnology is the one of the most strategies which were used to overcome the mentioned problem. In this study, it was tried to overcome the mentioned limitation though application of chitosan-coated solid lipid nanoparticles (SLNs).SLNs were prepared through solvent diffusion technique; here a relatively small volume of lipid phase (stearic acid, glyceryl mono stearate and stabilizer in ethanol) is diffused in a relatively large volume of aqueous phase at stirring condition and higher temperature. Invitro characteristics of the formed nanoparticles were determined via different analysis such as loading calculations, SEM image, DSC, FTIR analysis and also drawing the release profile of the drug.The optimized particle sizes of drug loaded SLNs and chitosan-coated SLNs were 105±6 nm and 142±11 nm respectively. The bigger particle size of last sample was due to chitosan-coating. The zeta potentials of these nanoparticles were calculated as -52mV and +23mV, respectively. The high negative sign of the SLNs was due to the anionic nature of the lipid fraction of its constituents and the positive value of the last sample was related to coating with cationic chains of chitosan polymer. SEM images of these nanoparticles showed nanometer scale of their sizes and also differences in their surface morphology due to branched coating of SLNs surfaces. These findings confirm the formation of such chitosan-coted SLNs. The entrapmentefficiency of these two nanocarriers were 18 and 34 %, respectively. The coating of hydrophobic SLN structure with a hydrophilic coat as chitosan could yield a more adjutant situation to encapsulate hydrophilic drugs. The data from DSC and FTIR analysis showed no unwanted interactions between lisinopril and nanocarriers. Although the electrostatic interactions of the negatively charged surface of SLNs and positively charged chitosan chains were proved via changes in their FTIR spectrums. Drawing of release profile of lisinopril from the uncoated and coated SLNs showed that where the 80 % of the drug was depleted in first 3 hours of release time in uncoated SLNs, this interval was elongated to 10 hours in chitosan-coated SLNs.The results of this study confirms the capability of chitosan-coating onto the surface of SLNs in order to control the drug release of a hydrophilic drug;lisinopril at sustain release manner.

Keywords:

Lisinopril , Solid lipid nanoparticles (SLN) , Chitosan , Burst release , Sustain release