Double-walled microspheres based on poly(lactide-co-glycolide) (PLGA) are potential delivery systems for reducing a very high initial burst release of encapsulated protein and peptide drugs. In this study, double-walled microspheres made of glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA), and carboxyl-terminated PLGA were fabricated using a modified water-in-oil-in-oil-in-water (w1/o/o/w2) emulsion solvent evaporation technique for the controlled release of a model protein, lysozyme. Microspheres size, morphology, encapsulation efficiency, lysozyme in vitro release profiles, bioactivity, and structural integrity, were evaluated. Scanning electron microscopy (SEM) images revealed that double-walled microspheres comprising of Glu-PLGA and PLGA with a mass ratio of 1:1 have a spherical shape and smooth surfaces. A statistically significant increase in the encapsulation efficiency (82.52% ± 3.28%) was achieved when 1% (w/v) polyvinyl alcohol (PVA) and 2.5% (w/v) trehalose were incorporated in the internal and external aqueous phase, respectively, during emulsification. Double-walled microspheres prepared together with excipients (PVA and trehalose) showed a better control release of lysozyme. The released lysozyme was fully bioactive, and its structural integrity was slightly affected during microspheres fabrication and in vitro release studies. Therefore, double-walled microspheres made of Glu-PLGA and PLGA together with excipients (PVA and trehalose) provide a controlled and sustained release for lysozyme.

Opioid dependency or tolerance is a worldwide problem that affects all societies in terms of health, social and economic welfare. It is a need to explore more alternative treatment to address opiate dependence and tolerance besides our current conventional medication. In exploring the alternative supplement to reduce opiate dependence and tolerance, this article reviews and describes the evidence of a relationship between mineral and opiate dependence and tolerance. We also discuss about the action mechanism of mineral to alleviate opiate dependence and tolerance which are abundantly available in the Holy Zamzam water.

MDMA (3, 4-methylenedioxymethamphetamine) is a psychoactive substance that is associated with neurotoxicity. MDMA exposure to human results in the degeneration of neuronal cells in the hippocampus. Hence, the purpose of this study was to examine the potential of a natural compound known as thymoquinone (TQ) to protect against neuronal damage and memory impairment in rats stimulated by MDMA. The administration of TQ into MDMA-induced neuronal damage rats was carried out in male Sprague Dawley via a 1-week treatment dividing into four groups (n=36, 7-9 per group). The studied groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (10 mg/kg MDMA), iii) MDMA+TQ (10 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ control (40 mg/kg TQ). A novel object recognition test (NORT) was carried out to evaluate the memory performance of the rats, followed by a histopathological assessment of the hippocampal dentate gyrus. The histopathology analysis revealed a significant increase in numbers of positive cells by Fluoro-Jade C following the effect of MDMA on neuronal damage (MDMA induced group) compared to control (P<0.05). Next, the TQ treatments observed in MDMA+TQ exhibited a decline in positive cells from Fluoro-Jade C. The index of recognition memory was found to be increased in MDMA+TQ compared to the MDMA alone (P<0.05). This study suggests that the neuronal damage inflicted by MDMA in a rat model has the potential to be treated by TQ.

Evaluation of Socioeconomic Status on Drug Addicted Person

Potassium voltage-gated channel subfamily H member 2 (KCNH2) polymorphisms have been found to influence the heart-rate adjusted QT (QTc) intervals. We investigated the association between KCNH2 polymorphisms and QTc intervals among Malay opioid-dependent methadone maintenance treatment (MMT) recipients. A cross-sectional study was conducted involving 111 patients with stable methadone dosage for at least 6 months attending several methadone clinics in Kelantan, Malaysia between March 2011 and October 2012. Those with cardiac structural defects, recipients of other QTc-prolonging pharmacotherapeutic agents, had aggressive behavior or other active psychiatric illnesses, chronic medical and surgical ailments and who were unable to communicate in Malay and English were excluded. The Fridericia-corrected QTc intervals were recorded using a 12-lead electrocardiogram. DNA samples were extracted from peripheral blood leukocytes and genotyped using nested allele-specific polymerase chain reaction for these four KCNH2 polymorphisms: 1539C > T, 1956T > C, 2350C > T, and 2690A > C. Mean QTc interval is 408 ms (SD: 24). Molecular docking was performed on all four KCNH2 polymorphisms to investigate the impact of the nucleotide changes on methadone binding. Based on multiple regression analysis, only 1539T > C polymorphism (β_adjusted: 10.506 (95% CI:0.846, 20.166), p = 0.033; recessive model), serum methadone trough (β_adjusted: 0.025 (95% CI: 0.006, 0.043), p = 0.009), potassium (β_adjusted: -8.756 (95% CI: -15.938, -1.575), p = 0.017) and magnesium (β_adjusted: -106.226 (95% CI: -159.291, -53.161), p < 0.001) levels were significantly associated with mean QTc. Molecular docking analysis resulted in good binding-energy values between the 1539C > T and methadone, with the formation of hydrophobic and π–π stacking interactions, suggesting that 1539C > T was the newly discovered SNP involved in QTc prolongation. In conclusion, the 1539C > T KCNH2 polymorphism is associated with QTc prolongation in our MMT recipients, necessitating QTc monitoring to prevent methadone-associated cardiotoxicity in this Malay MMT population.