Biodegradable Polymeric Biomaterials in Different Forms for Long-acting Contraception and Drug Delivery to the Eye and Brain

Efficacy of many of the new and existing therapeutics is often hampered by the lack of an effective and compliant method of delivery. Typically, drugs have poor water solubility, short half-lives, and low permeability across the biological membranes. The result is low bioavailability of the drugs at the target site and can cause toxicity and side effects at high doses. Often the conventional dosage forms fail to overcome these limitations. In the recent decades, biodegradable polymeric drug delivery systems have emerged as promising candidates to solve the challenges of poor solubility, low permeability and sustained release owing to the advantages of biocompatibility, versatility, and tunable drug release. Polyesters and polysaccharides are the most common polymers that were explored for drug delivery applications because of their unique advantages including non-toxic nature, wide availability, relatively low cost, and flexibility in chemistry. Although a major progress has been in the field of drug delivery, still there are unmet medical needs which require new materials for delivering drugs such as, injectable systems that can achieve long-term contraception (five months or longer) at low cost, and drug delivery systems that can enhance the permeability of drugs across ocular/blood-brain barriers and sustain release as well for treating chronic diseases such as diabetic retinopathy in the eye and Alzheimer’s disease in the brain. Therefore, this research has evaluated the potential of different biodegradable polymeric biomaterials based on polyesters or polysaccharides for long-acting contraception and drug delivery to the eye and brain to resolve the issues such as poor compliance and adherence to the existing contraceptive dosage forms or poor solubility and permeability of the drugs across ocular/blood-brain barriers. The first system includes polyester-based injectable in situ forming depot systems (ISD) for long-acting contraception. The aim of this project was to develop injectable ISD system containing levonorgestrel (LNG) for contraceptive effect for five months or longer after single shot that helps to reduce unintended pregnancies with high patient compliance and low cost. A series of LNG-containing ISD formulations were designed by employing unique strategies which include the use of poly(lactic acid-co-glycolic acid), poly(lactic acid) with different biodegradable properties, and blends of these polyesters, use solvent mixtures of N-methyl-2-pyrrolidone, triethyl citrate, benzyl benzoate, and vary the polymer/solvent ratios, and various drug loadings. The formulations were evaluated for viscosity, initial burst, in vitro and in vivo long-term release. In vivo investigation in rats showed the sustained-release pharmacokinetic profile of LNG from the ISD formulations for at least five months and continued for more than seven months depending on the composition, and the vaginal cytology studies have demonstrated that formulations have successfully suppressed the rat estrous cycle. After the end of the treatment, a rapid and predictable return of fertility was observed in rats. The optimized lead formulation has shown promising injectability (23 G) and low initial in vivo burst profiles. The results suggested that the developed LNG-ISD formulations have a great potential for developing into future robust affordable long-acting contraceptive products for improving patient compliance and adherence. Another type of polymeric biomaterial systems that were evaluated in this study includes polysaccharide-based biodegradable nanoparticles for drug delivery across ocular and blood-brain barriers. Depending on the need of the therapeutic application, two types of polysaccharide-based nanoparticles were investigated for their drug delivery feasibility which includes: (a) Poly(N-isopropylacrylamide-co-Dextran-lactateHEMA) nanogels for the potential delivery of hydrophilic peptide (insulin) across ocular barriers for the treatment of diabetic retinopathy. The in vitro, and ex vivo studies showed that the developed nontoxic nanogels have great potential to enhance the drug permeability across ocular barriers including the in vitro retinal pigment epithelium, sclera and cornea barriers for treating diabetic retinopathy; and (b) β-cyclodextrin-poly(β-amino ester) nanoparticles as potential drug carriers to enhance the solubility and blood-brain barrier (BBB) permeability of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) to treat Alzheimer’s disease. The nanoparticles sustained the release of 17-AAG for at least one week in vitro and showed increased permeability (2-fold) of the 17-AAG across BBB in vivo in mice, and resulted in enhanced expression of the Hsp70 protein in the brain. In conclusion, the developed biodegradable polymeric biomaterials have shown potential to be used in long-acting contraception and drug delivery to the eye and brain

Study of ascitic fluid cytology in ovarian tumors

Background: The objectives of this study were to examine the validity of ascitic fluid cytology in the detection of pathological findings, to examine the percentage of false positive and false negative results in the cytology of ascitic fluid and to determine the validity of peritoneal cytology in relation to the histopathological type of the ovarian tumour.Methods: This retrospective study, over a period of 6 months, included 106 peritoneal cytology findings. The experimental group included 106 cytology findings obtained from patients who presented with an abdominal lump/mass with ascites and diagnosed with ovarian tumors clinically. They included 88 benign ovarian tumours (83%) and 18 malignant ovarian tumors (17%). Patients with other causes of ascites were excluded from the study.Results: The sensitivity of peritoneal cytology is 90%, specificity is 96.5%, positive predictive value is 85.7%, and negative predictive value is 97.6%. In 1.8% of patients, the peritoneal cytology showed false negative results, while in 2.8%, the results were false positive. False negative results were found in one case of teratoma with squamous cell carcinoma and one case of yolk sac tumor. False positive results were found in 2 cases of tuberculous-salpingo- oophoritis and one case of chronic salpingo-oophoritis due to reactive mesothelial proliferation, mistaken for adenocarcinoma.Conclusions: Peritoneal cytology of ascitic fluid is highly specific and sensitive for detection of ovarian malignancies, particularly in grade 3 and grade 4 disease, since most of the patients with ovarian malignancies present to us at advanced stage of the disease

Nature Quotes

Recent days an increasing number of mobile applications and its uploading of photos/images shows that normal in every mobile application, so here is the latest idea we come up with an image/photo uploading with some quotation display on top of the image/photo from the selection of predefined feature quote data bank, and also we can add some user defined inspirational quotes to data bank for further usage and this will be like displaying of photos in slide show manner based on user setup. In this paper, we present an automatic approach that first aligns the photos and displays to the user based on random manner and this will also set up the display of quote and background sequentially, randomly, or fixed on certain one they selected. A user interactive application that can process addition or modification to the feature data bank like photos uploading and quotes changing. Also user can set the speed limit to the slide show to display background and its feature quote and this we are developing with both the versions of android and IOS environments

Prospective study of uterine corpus lesions over a period of one year in tertiary care centre

Background:Hysterectomy is the most commonly performed gynaecological surgery throughout the world. Few studies have been performed describing the pathologic findings in hysterectomy specimens and examining the relationship between the preoperative clinical indication, gross findings and pathologic diagnosis. This study was undertaken to identify the different types of pathologies in hysterectomy specimens and to correlate the findings with the clinical indications and gross findings.Methods: In the present study, five hundred and forty four cases were studied over a period of one year. Surgical specimens were formalin fixed and the tissue was adequately processed for histopathological examination. The sections were stained routinely with hematoxylin and eosin stain.Results: Menorrhagia and fibroid uterus were the most common clinical indications for hysterectomy. Of the 544 cases, 52.75% cases were encountered in the age group of 40 - 49 years which was the most common age group.  The most common pathology identified was leiomyoma in myometrium. Histopathological examination confirmed the clinical and gross diagnosis in majority of the cases.Conclusions: The present study provides a fair insight into the histological patterns of lesions in hysterectomy specimens in our institution. A wide range of lesions are encountered when hysterectomy specimens are subjected to histopathological examination. Though the histopathological analysis correlates well with the clinical and gross diagnoses, a few lesions were also encountered as incidental findings and mismatch diagnoses. Hence, it is mandatory that every hysterectomy specimen should be subjected to detailed gross and histopathological examination to ensure proper postoperative management of patients.

Role of FNAC in the diagnosis of cervical lymphadenopathy

Background: Cervical lymphadenopathy is one of the commonest presentations in inflammatory and neoplastic disorders. Fine Needle Aspiration Cytology (FNAC) is simple, quick, inexpensive and minimally invasive OPD technique used for establishing the etiology of cervical lymphadenopathy. In this study we describe cytomorphological patterns of cervical lymph nodes and its utility in establishing diagnosis. Objectives of present study were to assess the distribution of various cytomorphological patterns of cervical lymphadenopathy and to assess the age specific distribution of various cytomorphological patterns of cervical lymphadenopathy.Methods: This study was carried out in the Department of Pathology, Andhra Medical College on 200 cases of cervical lymphadenopathy over a period of three months from August - October 2017. FNAC diagnosis was correlated with relevant clinical findings and investigations.Results: Total 200 cases were studied. Of these, 170 (85%) were inflammatory and 30 (15%) were neoplastic. Reactive non-specific lymphadenitis was the most common disease found in 95 (47.5%) patients followed by tuberculous lymphadenitis in 60 patients (30%) and granulomatous lymphadenitis in 15 patients (7.5%). Among neoplastic lesions, metastatic tumours were reported in 26 patients (13%) and Lymphoproliferative disorder/Lymphoma was reported in 4 patients (2%). Highest incidence of cervical lymphadenopathy was found in patients of 10-39 years age group, among which most of the cases were non-specific lymphadenitis followed by tuberculous lymphadenitis. Amongst the neoplastic lesions, most of the cases were in the age group of 40-79 years.Conclusions: FNAC is simple, safe, reliable procedure for diagnosis of cervical lymphadenopathy. 

A Study on Psychiatric Disorders and Mental Health Service Use Among Spouses of Advanced Cancer Patients

Aim & Objective: 1.To study the frequency and nature of psychiatric disorders in spouses of cancer patients. 2.To know the relationship between the perceived psychopathology and quality of life of spouses where one is diagnosed with cancer. Methodology: This is a case control observational clinical study assessing the frequency and nature of psychiatric illness in spouses of cancer patients in comparison with spouses of BPAD patients. Results: In the present study, the most common age group to which the cancer patients and their spouses belonged to was 51-64 years whereas the BPAD patients and their spouses belonged to age group of 31-40 years. Most common diagnosis of the cancer patients (whose spouses are being studied) was head and neck cancer (46%)., In the present study psychiatric morbidity is seen in upto 54% of cancer patient spouses and the similar was observed in BPAD spouses .i.e 53.3%.MDD (major depressive disorder) (55.6%) was found to be the most common psychiatric diagnosis followed by adjustment disorder (25.9) in cancer patient spouses..Other psychiatric disorders are generalised anxiety disorder, dysthymia and panic disorder. Adjustment disorder followed by Major depressive disorder was found to be the most common psychiatric diagnosis in BPAD patients. Both cases and controls also had high levels of psychopathology scores without a psychiatric diagnosis. Quality of life was less in the subjects with a psychiatric diagnosis than the ones without a psychiatric diagnosis. Severity and frequency of psychopathology in case and control group was inversely related to quality of life i.e that severe psychopathology tend to have low quality of life. Psychiatric morbidity was more common in spouses of head and neck cancer patients. Female’s spouses of cancer patients had low social functioning when compared to males. Spouses of cancer patients aged between 31-40 years had lower quality of life when compared to other age groups. Conclusion: The present study also highlights the need for spouses’ psychiatric evaluation after a person is diagnosed with cancer and the need for further research in this field in India as well as other nations

An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months