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A biocompatible, biodegradable and FDA-approved polymer [Poly lactic-co-glycolic acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of solvents, stabilizers and their concentrations on the physical properties of the PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects of different proportions of PVA/PVP with DCM/chloroform on the physiochemical properties (particle size, the polydispersity index, the zeta potential by Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was used to check the physical state, the possible complexation of PLGA with stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. Average size of 273.2–563.9 nm was obtained when PVA (stabilizer) with DCM, whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 273.2–563.9 nm when PVP was the stabilizer with DCM, while it was 381.4–466.6 nm with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative (−0.62 mV) while they were comparatively higher and positive for PVP-stabilized NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1–3%), which resulted in sufficient encapsulation (54.94–74.86%) and drug loading (4.99–6.81%). No endothermic peak of PVA/PVP appeared in the optimized formulation, which indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro release study indicated a sustained release of IND (32.83–52.16%) from the PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics followed by Korsmeyer–Peppas models. The cell proliferation assay clearly established that the organic solvents used to prepare PLGA-NPs had evaporated. The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the dose range of IND (250–500 µg/mL) and at an equivalent concentration of PLGA-NPs (3571.4–7142.7 µg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced by its encapsulation into PLGA-NPs. The outcomes of this investigation could be implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of low/high molecular weight drugs. It would be useful for further in vitro and in vivo applications to use this delivery system. [ABSTRACT FROM AUTHOR]

Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = −18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m2/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly (p < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations. [ABSTRACT FROM AUTHOR]