Sleep Quality in relation with Perceived Stress and Physical Activity in the Students of Pakistani Medical Colleges

Background: Sleep is an essential function of our body. Many surveys have reported the prevalence of poor sleep in university students, especially in medical students.  Objectives: The objective of the study was to evaluate the effect of physical activity and stress on sleep quality among medical students in Pakistan. Materials & Methods: An observational cross-sectional study was conducted on medical students of private medical colleges in Lahore. A convenient sampling technique was used and 210 students were selected. The Pittsburgh Sleep Quality Index (PSQI), Godin Shephard Leisure Time Physical Activity Questionnaire (GSLTPAQ), and Perceived Stress Scale (PSS 10) were used for data collection. We used SPSS version 20 to analyze data and applied statistical tests: Chi-square test and Logistic Regression.  p-value < 0.05 was taken to establish significance. Results: Among the study participants 91(43.3%) were males and 119 (57.7%) were females. There was a significant effect of stress level on sleep quality (P=0.000*). The frequency of good sleepers was seen to increase by almost three times with increasing physical activity, however, this difference remained non-significant (p=0.07). The logistic regression test showed a significant relationship between poor sleep and stress (p=0. 008**) while no significant relationship was seen between sleep quality and physical activity. Conclusion: There was a significant association between poor sleep and high-stress levels and an increase in physical activity showed an increase in the frequency of good sleep, however, this difference was non-significant. It can be inferred that this positive effect of increasing physical activity on the quality of sleep could be indirectly due to its relieving effect on stress.  

Macromolecular Prodrugs of Some Antibiotics onto Polyglucans: Fabrication, Characterization, Applications and Studies of Nano-Assemblies in Solution

Present study reports the synthesis and characterization of hydroxypropylcellulose (HPC) based macromolecular prodrugs (MPDs) of a broad spectrum class of antibacterial agents; fluoroquinolones. Prodrugs of some fluoroquinolones, i.e., moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin were fabricated as ester conjugates of HPC in various mole ratios using p-toluenesulfonyl chloride as carboxylic acid activating agent. All prodrugs were found organo- as well as water-soluble. Structural characterization of HPC-fluoroquinolone conjugates 1-17 was carried out by FTIR, 1H, 13 C and 2D NMR spectroscopic techniques. Covalently loaded drug content (DC) of the conjugates was determined by UV/Vis spectrophotometry as well as by HPLC/UV method. Degree of substitution (DS) of the conjugates was derived from the respective DC of each conjugate. DS of all conjugates was also determined by acid-base titration after saponification and found to be 0.27-0.38, 0.53- 0.71, 0.57-0.64 and 0.87-1.15 per AGU for moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin, respectively. Nano-assembly behavior of HPC-fluoroquinolone conjugates at solvent interface (DMSO/H2O) was assessed by transmission electron microscopy (TEM). TEM images showed that HPC-fluoroquinolone conjugates behaved differently; HPC- moxifloxacin conjugate 3 self-assembled into nanowires of 30 nm diameter, while HPC- ofloxacin conjugate 7, HPC-levofloxacin conjugate 11 and HPC-ciprofloxacin conjugate 15 self-assembled onto nanoparticles having diameter range of 200-270, 50-250 and 150-250 nm, respectively. In vitro drug release studies revealed higher release from prodrugs in simulated intestinal fluid (SIF) as compared to simulated gastric fluid (SGF). Conjugates 3, 7, 11 and 15 showed release of 49, 39, 44 and 43%, respectively, in SIF after first 6 h. While these conjugates showed only 12-15% release in SGF in the same time period. Higher release in SIF confirmed that the synthesized prodrugs could be used as devices for achieving colon targeted drug delivery. Pharmacokinetic studies of the conjugates in rabbit models indicated enhanced bioavailability of the respective drugs. Following single oral dose, conjugates 3, 7, 11 and 15 showed half-life of 25.20, 18.07, 18.08 and 10.87 h, respectively. These enhanced half-life values suggest the potential of the fabricated MPDs for once daily dosage formulation. Thermal analyses of the synthesized prodrugs were carried out to assess their pharmaceutical performance parameters. Thermal stability of HPC, drugs and prodrugs was compared in terms of thermal degradation temperatures (Tdi, Tdm,Tdf). Comparable Tdm values of drugs and conjugates suggested that no thermal stress was developed after the attachment of bulky drug molecules to polymer backbone. Thermal stability of conjugates was also evaluated in terms of integral procedure decomposition temperature (IPDT) and index of thermal stability (ITS). Conjugate 3, 7, 11 and 15 showed IPDT values of 450, 442, 464 and 486 °C, respectively. The ITS values were found to be 0.51, 0.52, 0.46 and 0.51, respectively, for these conjugates. Significantly higher IPDT and ITS values also confirmed the intrinsic thermal stability of these conjugates. Modulated differential scanning calorimetry was also performed to analyze glass-transition temperatures (Tg) imparted due to attachment with polymer. Tg values observed were 111.60, 84.16, 113.85 and 61.91 °C for conjugates 3, 7, 11 and 15, respectively. PXRD studies confirmed that some crystallinity was imparted to MPDs of fluoroquinolones. Powder X-ray analysis also confirmed the amorphous characteristics of the conjugates. Therefore, such MPDs can be used for colon targeted delivery of fluoroquinolones with enhanced bioavailability and reduced dosage frequency.