Enhanced Gastric Tolerability And Improved Anti-obesity Effect Of Capsaicinoids-loaded PCL Microparticles

Enhanced gastric tolerability and improved anti-obesity effect of

capsaicinoids-loaded PCL microparticles

Martinha A. Almeida a, Jessica M. Nadal a, SabrinaGrassiolli b, Katia S. Paludo a, Sônia F. Zawadzki c, Letícia Cruz d,

Josiane P. Paula a, Paulo V. Farago a,⁎

a Postgraduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Brazil

b Department of General Biology, State University of Ponta Grossa, Brazil

c Department of Chemistry, Federal University of Paraná, Brazil

d Department of Industrial Pharmacy, Federal University of Santa Maria, Brazil

a r t i c l e i n f o a b s t r a c t

Article history:

Received 23 September 2013

Received in revised form 10 March 2014

Accepted 21 March 2014

Available online 30 March 2014

Keywords:

Capsaicin

Controlled-release carriers

Dihydrocapsaicin

Low-irritative oral preparation

Poly(ε-caprolactone)

Weight-loss strategy

Capsaicinoids show several pharmacological effects including weight loss. However, their pungency limits the

long-term use through the gastrointestinal tract. In that sense, the goal of this study was to prepare

capsaicinoids-loaded poly(ε-caprolactone) microparticles as an oral carrier in order to improve their gastric tolerability

and to make feasible the long-term treatment of obesity. Formulations containing 3, 5 and 10%

capsaicinoids were successfully obtained by simple emulsion/solvent evaporation method. Values of encapsulation

efficiency above 90% were achieved. Microparticles showed spherical shape and smooth surface. The particle

sizewas suitable for oral use in order to provide an extended release through the gastrointestinal tract. No chemical

bondwas observed between drug and polymer.Microencapsulation led to drug amorphization. Formulations

prolonged the release of capsaicinoids without changing the release kinetic (biexponential model).Microencapsulation

increased the gastric tolerability of capsaicinoids because it prevented inflammatory processes in the

stomach of rats. Microparticles containing 5% capsaicinoids demonstrated a statistically significant reduction of

Lee index, mesenteric and retroperitoneal fat pads of rats with obesity induced by hypothalamic lesion using

monosodium L-glutamate. In summary, capsaicinoids-loaded poly(ε-caprolactone) microparticles are lowirritative

oral controlled-release carriers for a long-term use in obesity.

© 2014 Elsevier B.V. All rights reserved.

1. Introduction

Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) and dihydrocapsaicin

(8-methyl-N-vanillylnonanamide) (Fig. 1) are the two most

pungent capsaicinoids from chili peppers (Capsicum spp.). These

capsaicinoids exert multiple pharmacological and physiological effects

including analgesic, anticancer, anti-inflammatory, antioxidant and

anti-obesity activities. Therefore capsaicinoids have a potential value

in clinic for pain relief, cancer prevention and weight loss [1].

A current systematic reviewreported that consumption of capsaicinoids

increases energy expenditure by about 50 kcal/day which produces a

clinically significant weight loss in 1–2 years [2]. It was also observed

that a regular use of capsaicinoids significantly reduced abdominal

adipose