Abstract
Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from −14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (p < 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.
Highlights
The development of effective technologies to enable the delivery of BCS (Biopharmaceutical Classification System) class IV drugs is a challenge, because the dissolution is a rate-limiting step for oral absorption [1]
Captopril-surface functionalized Multi-wall lipid-core nanocapsule (MLNC) and captopril-surface functionalized furosemide-loaded MLNC were developed in four steps: (a) self-assembling of the materials, (b) chitosan coating, (c) Zn2+ interfacial reaction and (d) complexation forming the ligand-Zn2+ organometallic complex on the nanocapsule surface
Six formulations of Capt(0.5)-Zn-MLNC-Fur(0.45) were prepared varying the concentrations of Zn2+ (0, 25, 50, 100, 200 and 400 μg mL−1) and maintaining constant the captopril concentration (0.5 mg mL−1)
Summary
The development of effective technologies to enable the delivery of BCS (Biopharmaceutical Classification System) class IV drugs is a challenge, because the dissolution is a rate-limiting step for oral absorption [1]. A few years ago, our research group proposed a new process to functionalize the surface of chitosan-coated lipid-core nanocapsules using a ligand-metal ion-chitosan-lecithin complex [27,28,29,30,31,32,33] This method is based on a rapid one-pot synthesis without needing any purification step, overcoming the drawbacks of other methodologies. The liquid formulation containing the laronidase-functionalized multiwall lipid-core nanocapsules showed a higher catalytic activity in vivo in liver, kidney and heart compared to the commercial product. Our hypothesis considered that their association in multiwall nanocapsules could bring improvements in treatment effectiveness To prove this concept, the pharmacodynamic effect and the toxicity of this innovative formulation (captopril-surface functionalized furosemide-loaded multiwall nanocapsules) administered by the oral route to spontaneously hypertensive rats were evaluated. The study constitutes the first investigation of the surface-functionalized nanocapsules administered by the oral route
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