Preparation and characterization of in-situ ionic cross-linked pectin films: II. Biodegradation and drug diffusion.

In the present study the enzymatic biodegradation of a series of calcium pectinate (CaP) films, produced by in-situ crosslinking of pre-formed low methoxy pectin films in a calcium chloride (CaCl2) solution, has been assessed. The degradation level was determined by measuring the concentration of short chain fatty acid salts (SCFA), which are the natural metabolites of pectin. To this end an ex-vivo model, mimicking the colon's environment, was utilized. The results showed that a fully calcified film from a high concentration of CaCl2 solution did not exhibit any tendency to biodegradability throughout the test time. Contrastively, a low concentration of the crosslinking solution resulted in fully calcified films which could clearly present considerably higher biodegradability. SEM analysis was used to characterize the surface of CaP films after an exposure to human feces. The permeability of CaP films to different model drugs was also tested.

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery.

Stimuli-responsive micelles have emerged as the drug carrier for cancer therapy since they can exclusively release the drug via their structural changes in response to the specific stimuli of the target site. Herein, we developed the in situ diselenide-crosslinked micelles (DCMs), which are responsive to the abnormal ROS levels of tumoral region, as anticancer drug carriers. The DCMs were spontaneously derived from selenol-bearing triblock copolymers consisting of polyethylene glycol (PEG) and polypeptide derivatives. During micelle formation, doxorubicine (DOX) was effectively encapsulated in the hydrophobic core, and diselenide crosslinks were formed in the shell. The DCMs maintained their structural integrity, at least for 6 days in physiological conditions, even in the presence of destabilizing agents. However, ROS-rich conditions triggered rapid release of DOX from the DOX-encapsulating DCMs (DOX-DCMs) because the hydrophobic diselenide bond was cleaved into hydrophilic selenic acid derivatives. Interestingly, after their systemic administration into the tumor-bearing mice, DOX-DCMs delivered significantly more drug to tumors (1.69-fold and 3.73-fold higher amount compared with their non-crosslinked counterparts and free drug, respectively) and effectively suppressed tumor growth. Overall, our data indicate that DCMs have great potential as drug carriers for anticancer therapy.

An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin.

The use of pectin for colon-specific drug delivery has been extensively investigated; however, when used alone, pectin is often compromised due to its high solubility. This study explored the feasibility of using an in situ compression-coated crosslinking system, composed of pectin and calcium chloride, for colon-specific drug delivery. A pectin/calcium chloride (P/Ca) coating was compressed onto a core tablet. The colon specificity of the compression-coated tablet was verified by dissolution, pharmacokinetics and scintigraphy with (99m)Tc labeling. The in situ pectin and calcium chloride gel slowed the release of indomethacin. The lag time varied between 3 h and 7 h depending on the amount of calcium chloride and the coating weight. Pectinase triggered the release of indomethacin from the compression-coated tablet, which was then accelerated by the calcium chloride in the coating layer. The compression-coated tablet had a prolonged tmax and apparent t1/2, as well as a decreased Cmax and AUC0-t, compared with the core tablet counterpart. Evaluation with γ-scintigraphy verified colon-specific delivery of the compression-coated tablet. In conclusion, the P/Ca in situ crosslinking system worked well for colon-specific drug delivery.

Preparation and characterization of in situ ionic cross-linked pectin films: unique biodegradable polymers.

The study aimed to investigate the swelling and degradation of calcium pectinate (CaP) films that were cross-linked by the innovative approach of adding aqueous calcium chloride (CaCl2) to pre-formed pectin films in situ. The films, cast from low methoxy pectin, were dried and cross-linked by immersion in a selected CaCl2 solution for a selected period. It was found that CaCl2 concentration, immersion time, and temperature affected the films' dissolution and swelling behaviors in simulated intestinal fluid. With lower CaCl2 concentration, more time was needed to form a proper film. Heat accelerated the cross-linking reaction, probably by elevating the cross-linked solution flux into the matrix. Depending upon cross-linking conditions, similar calcium contents in the CaP films resulted in different swelling and degradation behaviors. The degree of pectin esterification (DE) affected the films' degradation rate. The role of pectin molecular weight and DE on the films' mechanical properties was determined by stress/strain analysis.