Optimizacija kitozanskih filmova kao zamjena za životinjsku i humanu epidermu za in vitro permeaciju polarnih i nepolarnih lijekova

The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.U radu je opisana priprava kitosanskih filmova pogodnih za simulaciju prijelaza modelnih lijekova, 5-fluorouracila (5-FU) i indometacina (INDO), kroz epidermalne slojeve štakora, zeca i čovjeka. Koncentracija kitosana, vrijeme umrežavanja i koncentracija reagensa za umrežavanje značajno su utjecale na in vitro prolaz 5-FU i INDO kroz kitosanske filmove. Multiplom linearnom regresijom pokazano je da sve navedene varijable imaju linearni utjecaj na prolaz 5-FU i INDO. Uz pomoć atomske apsorpcijske spektralne analize, DSC i IR spektroskopskih podataka zaključeno je da je 5%-tna (m/V) otopina natrijevog tripolifosfata (NaTPP) najoptimalnija za umrežavanje kitosanskih filmova. Pronađeno je da je in vitro permeacija 5-FU i INDO kroz optimiziranu formulaciju kitozanskog filma usporediva s permeacijom kroz epidermalne slojeve štakora, zeca i čovjeka. Rezultati upućuju da se optimizirani kitozanski filmovi mogu upotrijebiti kao nadomjestak animalne i humane epiderme u preliminarnim in vitro permeacijskim istraživanjima

Optimizacija kitozanskih filmova kao zamjena za životinjsku i humanu epidermu za in vitro permeaciju polarnih i nepolarnih lijekova

The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.U radu je opisana priprava kitosanskih filmova pogodnih za simulaciju prijelaza modelnih lijekova, 5-fluorouracila (5-FU) i indometacina (INDO), kroz epidermalne slojeve štakora, zeca i čovjeka. Koncentracija kitosana, vrijeme umrežavanja i koncentracija reagensa za umrežavanje značajno su utjecale na in vitro prolaz 5-FU i INDO kroz kitosanske filmove. Multiplom linearnom regresijom pokazano je da sve navedene varijable imaju linearni utjecaj na prolaz 5-FU i INDO. Uz pomoć atomske apsorpcijske spektralne analize, DSC i IR spektroskopskih podataka zaključeno je da je 5%-tna (m/V) otopina natrijevog tripolifosfata (NaTPP) najoptimalnija za umrežavanje kitosanskih filmova. Pronađeno je da je in vitro permeacija 5-FU i INDO kroz optimiziranu formulaciju kitozanskog filma usporediva s permeacijom kroz epidermalne slojeve štakora, zeca i čovjeka. Rezultati upućuju da se optimizirani kitozanski filmovi mogu upotrijebiti kao nadomjestak animalne i humane epiderme u preliminarnim in vitro permeacijskim istraživanjima

Engineered Site Specific Vesicular Systems for Colonic Delivery: Trends and Implications

Steering drug loaded, site-specific, coated lipid vesicles to the target receptor sites has the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of large bowel, especially colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight and peptidase activity in the stomach. Consequently, colon specific coated liposomal systems (CSLS) offer a potential alternate for not only site specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes and issues related to production at pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite these ostensible propitiousnesses, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS have quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery

Lipid synthesis inhibitors: Effect on epidermal lipid conformational changes and percutaneous permeation of levodopa

A combination of lipid synthesis inhibitors was used to enhance the in vitro and in vivo permeation of levodopa (LD) across rat epidermis, and their influence on epidermal lipids was investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Rat epidermis was treated with ethanol and a combination of atorvastatin (750 μg/7 cm2), cerulenin (20 μg/7 cm2), and β-chloroalanine (600 μg/7 cm2) for sustaining the reduced content of epidermal cholesterol, fatty acids (as triglycerides), and ceramide (as sphingosine), respectively, in viable rat skin. This treatment resulted in significant (P<.05) synthesis inhibition of skin lipids up to 48 hours and 6-fold enhancement in the in vitro permeation of LD. The effective plasma concentration of LD was achieved within 1 hour and maintained over 48 hours after topical application to rat epidermis treated with a combination of these lipid synthesis inhibitors. ATR-FTIR studies of inhibitor(s)-treated rat epidermis revealed a significant decrease (P<.05) in peak height and area for both asymmetric and symmetric C−H stretching absorbances, suggesting extraction of lipids. However, an insignificant (P<.05) shift in the frequency of these peaks suggested no fluidization of epidermal lipids by lipid synthesis inhibitors. A direct correlation was observed between epidermal lipid synthesis inhibition, decrease in peak height or area, and percutaneous permeation of LD. Skin lipid synthesis inhibition by a combination of lipid synthesis inhibitors seems to offer a feasible approach for enhancing the transcutaneous delivery of LD