Effect of Polyethylene Glycol on Properties and Drug Encapsulation–Release Performance of Biodegradable/Cytocompatible Agarose–Polyethylene Glycol–Polycaprolactone Amphiphilic Co-Network Gels

We synthesized agarose–polycaprolactone (Agr-PCL) bicomponent and Agr–polyethylene glycol–PCL (Agr-PEG-PCL) tricomponent amphiphilic co-network (APCN) gels by the sequential nucleophilic substitution reaction between amine-functionalized Agr and activated halide terminated PCL or PCL-<i>b</i>-PEG-<i>b</i>-PCL copolymer for the sustained and localized delivery of hydrophilic and hydrophobic drugs. The biodegradability of the APCNs was confirmed using lipase and by hydrolytic degradation. These APCN gels displayed good cytocompatibility and blood compatibility. Importantly, these APCN gels exhibited remarkably high drug loading capacity coupled with sustained and triggered release of both hydrophilic and hydrophobic drugs. PEG in the APCNs lowered the degree of phase separation and enhanced the mechanical property of the APCN gels. The drug loading capacity and the release kinetics were also strongly influenced by the presence of PEG, the nature of release medium, and the nature of the drug. Particularly, PEG in the APCN gels significantly enhanced the 5-fluorouracil loading capacity and lowered its release rate and burst release. Release kinetics of highly water-soluble gemcitabine hydrochloride and hydrophobic prednisolone acetate depended on the extent of water swelling of the APCN gels. Cytocompatibility/blood compatibility and pH and enzyme-triggered degradation together with sustained release of drugs show great promise for the use of these APCN gels in localized drug delivery and tissue engineering applications

Utility of the RIPS scale and 2CAN score for in-hospital stroke prediction

Background: In-hospital strokes are a small but sizeable proportion of all strokes. Identification of in-hospital strokes is confounded by stroke mimics in as many as half of in-patient stroke codes. A quick scoring system based on risk factors and clinical signs during the initial evaluation of a suspected stroke might be helpful to distinguish true strokes from mimics. Two such scoring systems based on ischemic and hemorrhagic risk factors are the risk for in-patient stroke (RIPS) and the 2CAN score. Materials and Methods: This prospective clinical study was conducted at a quaternary care hospital in Bengaluru, India. All hospitalized patients aged 18 years and above for whom a “stroke code” alert was recorded during the study period of January 2019 to January 2020 were included in the study. Results: A total of 121 in-patient “stroke codes” were documented during the study. Ischemic stroke was the most common etiological diagnosis. A total of 53 patients were diagnosed to have ischemic stroke, 4 had intracerebral hemorrhage, and the rest were mimics. Receiver operative curve analysis was performed and at a cut-off of RIPS ≥3, it predicts stroke with a sensitivity of 77% and a specificity of 73%. At a cut-off of 2CAN ≥3, it predicts stroke with a sensitivity of 67% and a specificity of 80%. RIPS and 2CAN significantly predicted stroke. Conclusions: There was no difference in the use of either RIPS or 2CAN for differentiating stroke from mimics, and hence they may be used interchangeably. They were statistically significant with good sensitivity and specificity, as a screening tool to determine in-patient stroke

PLGA Microspheres of hGH of Preserved Native State Prepared Using a Self-Regulated Process

The challenges of formulating recombinant human growth hormone (rhGH) into sustained-release polymeric microspheres include two mutual causal factors, protein denaturing by the formulation process and severe initial burst release related with relative high dose. The stabilizers to protect the proteins must not evoke osmotic pressure inside the microspheres, and the contact of the protein with the interface between water and organic solution of the polymer must be minimized. To meet these criteria, rhGH was pre-formulated into polysaccharide particles via an aqueous&ndash;aqueous emulsion in the present study, followed by encapsulating the particles into microspheres through a self-regulated process to minimize the contact of the protein with the water&ndash;oil interface. Polysaccharides as the protein stabilizer did not evoke osmotic pressure as small sugar stabilizers, the cause of severe initial burst release. Reduced initial burst enabled reduced protein loading to 9% (from 22% of the once commercialized Nutropin depot), which in turn reduced the dosage form index from 80 to 8.7 and eased the initial burst. A series of physical chemical characterizations as well as biologic and pharmacokinetic assays confirmed that the present method is practically feasible for preparing microspheres of proteins

Association of the MMP1–1607 1G>2G, MMP3-1171 5A>6A and MMP9-1562 C>T genotypes with breast cancer susceptibility and clinicopathological characteristics.

<p>Association of the MMP1–1607 1G>2G, MMP3-1171 5A>6A and MMP9-1562 C>T genotypes with breast cancer susceptibility and clinicopathological characteristics.</p

Synergistic effect of collagenase-1 (MMP1), stromelysin-1 (MMP3) and gelatinase-B (MMP9) gene polymorphisms in breast cancer

<div><p>Background</p><p>Extracellular matrix degradation by matrix metalloproteinases (MMPs) is an important mechanism involved in tumor invasion and metastasis. Genetic variations of MMPs have shown association with multiple cancers. The present study is focused to elucidate the association of MMP-1, 3 and 9 genetic variants with respect to epidemiological and clinicopathological variables by haplotype, LD, MDR, survival in silico analyses among South Indian women.</p><p>Material and methods</p><p>MMP3–1171 5A/6A and MMP9–1562 C/T SNPs were genotyped by Allele specific polymerase chain reaction and MMP1-1607 1G/2G polymorphism by restriction fragment length polymorphism assays respectively, in 300 BC patients and age-matched 300 healthy controls. Statistical analysis was performed using the SNPStats and SPSS software. Linkage disequilibrium and gene-gene interactions were performed using Haploview and MDR software respectively. Further, transcription factor binding sites in the promoter regions of SNPs under study were carried out using AliBaba2.1 software.</p><p>Results</p><p>We have observed an increased frequency of 2G-allele of MMP1, 6A-allele of MMP3 and T-allele of MMP9 (p<0.05) respectively in BC subjects. The 2G-6A haplotype (minor alleles of MMP-1 and MMP-3 respectively) has shown an increased susceptibility to BC. Further, MMP polymorphisms were associated with the clinical characteristics of BC patients such as steroid hormone receptor status, lymph node involvement and metastasis. SNP combinations were in perfect LD in controls. MDR analysis revealed a positive interaction between the SNPs. 5-years survival rate and cox-regression analysis showed a significant association with clinicopathological variables.</p><p>Conclusion</p><p>Our results suggest that MMP1–1607 1G/2G, MMP3–1171 5A/6A and MMP9–1562 C/T gene polymorphisms have synergistic effect on breast cancer. The interactions of MMPs clinical risk factors such as lymph node involvement has shown a strong correlation and might influence the 5-years survival rate, suggesting their potential role in the breast carcinogenesis.</p></div

Clinicopathological parameters among the breast cancer patients.

<p>Clinicopathological parameters among the breast cancer patients.</p

Summary of gene-gene interaction by MDR analysis.

<p>Summary of gene-gene interaction by MDR analysis.</p

Genotype and allele frequencies distribution for MMP-1, MMP-3 and MMP-9 gene polymorphisms in controls and breast cancer subjects.

<p>Genotype and allele frequencies distribution for MMP-1, MMP-3 and MMP-9 gene polymorphisms in controls and breast cancer subjects.</p

Interaction dendrogram of SNP-SNP by MDR analysis.

<p>Interaction dendrogram of SNP-SNP by MDR analysis.</p