The slow release of BMP-7 at a low dose accelerates dental implant healing in an osteopenic environment

The aim of the present study was to investigate in vivo whether bone morphogenetic protein-7 (BMP-7) was able to promote and accelerate dental implant healing at a low dose in an osteopenic environment by using a delayed drug-release system. Skeletally mature Chinese goats, having physiologically osteopenic (osteoporotic-like) facial bones, served as an animal model. Dental implants were provided with a delayed-release drug-delivery system and BMP-7 was applied at three different dosages. The implants, inserted into healed extraction sockets, were removed 1, 2 and 3 weeks after surgery. Quantification of osseointegration and formation of new bone in the peri- implant space were measured histomorphometrically. Data revealed no evidence of any adverse drug effect at or near the implantation sites. After the first postoperative week, bone neoformation was minimal; after the second week, peri-implant bone formation appeared, particularly in the groups with low dosages of BMP-7. After 3 weeks, new-bone volume was the largest in the group with the lowest (near-physiological) dosage of BMP-7, also showing the highest efficacy of BMP-7. Other dosage or release modes were found to be significantly less effective. BMP-7 was highly efficacious in promoting and accelerating bone formation in the peri-implant space in a hostile osteopenic environment if released by a slow-mode mechanism over time at near physiological activities. Therefore, biological functionalisation of dental implants by a high-power osteogenic factor may improve their healing success in hostile bony environments (osteopenia, osteoporosis, bone atrophy etc.).

Pectin-Coated Curcumin-Chitosan Microparticles Crosslinked with Mg2+ for Delayed Drug Release in the Digestive System

Curcumin-loaded chitosan-pectin microparticles based on polymeric microencapsulation were prepared by two methods to delay the release of curcumin in the digestive system, employing Mg2+ as a pectin-crosslinking agent for the first time. Pectin-coated curcumin-chitosan microparticles (C-g-PMg) and curcumin-loaded chitosan-pectin composite microparticles (C-PMg-g) were formulated, and their release profiles at pH 1.2 and at pH 6.8 were tested. The former (C-g-PMg) showed slower curcumin release profiles than the latter (C-PMg-g) because the C-g-PMg are composed of two layers, a chitosan-glutaraldehyde layer and a pectin-Mg2+ layer, which together hold the curcumin for a longer duration. Of the pectin-coated microparticles, those crosslinked with Mg2+ showed a slower release rate than those crosslinked with Ca2+, but the former showed a faster release rate at pH 6.8 in the presence of pectinase, acting as a promising drug delivery carrier for treating a colonic disease. The pectin layer and the pectin-crosslinking agent play a vital role in prolonging the release of curcumin until pectin is degraded by pectinase.

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery.