ABSTRACT
This study aimed to design and evaluate enhanced permeation and retention (EPR)-mediated anticancer effect of polymer-modified and drug-loaded magnetite nanocomposites. The preformulated bare (10 nm), chitosan-superparamagnetic iron oxide (SPIO; 69 nm), heparin-SPIO (42 nm), and (3-aminopropyl)triethoxysilane-polyethylene glycol-SPIO (17 nm) nanocomposites were utilized to evaluate the EPR-mediated localized cancer targeting and retention of doxorubicin (DOX) and paclitaxel (PTX) in human ovarian cancer cell lines, A2780 and OVCAR-3 in vitro and in the tumor-baring Balb/c mice in vivo. Fluorescence microscopy showed that DOX- and PTX-loaded SPIO nanoparticles caused long-term accumulation and cytoplasmic retention in A2780 and OVCAR-3 cells, as compared to free drugs in vitro. In vivo antiproliferative effect of present formulations on immunodeficient female Balb/c mice showed a tremendous amount of ovarian tumor shrinkage within 6 weeks. The present nanocomposite systems of targeted drug delivery proved to be efficient drug carrier with sustained drug release and long-term retention with enhanced cytotoxic properties in vitro and in vivo.
Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Drug Carriers/administration & dosage , Magnetite Nanoparticles/administration & dosage , Ovarian Neoplasms/drug therapy , Animals , Cell Line, Tumor , Chitosan/chemistry , Female , Humans , Mice, Inbred BALB C , Mice, SCID , Polyethylene Glycols/chemistry , Propylamines/chemistry , Silanes/chemistryABSTRACT
Magnetite nanoparticles are particularly attractive for drug delivery applications because of their size-dependent superparamagnetism, low toxicity, and biocompatibility with cells and tissues. Surface modification of iron oxide nanoparticles with biocompatible polymers is potentially beneficial to prepare biodegradable nanocomposite-based drug delivery agents for in vivo and in vitro applications. In the present study, the bare (10 nm) and polyethylene glycol (PEG)-(3-aminopropyl)triethoxysilane (APTES) (PA) modified (17 nm) superparamagnetic iron oxide nanoparticles (SPIO NPs) were synthesized by coprecipitation method. The anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately encapsulated into the synthesized polymeric nanocomposites for localized targeting of human ovarian cancer in vitro. Surface morphology analysis by scanning electron microscopy showed a slight increase in particle size (27 ± 0.7 and 30 ± 0.45 nm) with drug loading capacities of 70 and 61.5 % and release capabilities of 90 and 93 % for the DOX- and PTX-AP-SPIO NPs, respectively (p < 0.001). Ten milligrams/milliliter DOX- and PTX-loaded AP-SPIO NPs caused a significant amount of cytotoxicity and downregulation of antiapoptotic proteins, as compared with same amounts of free drugs (p < 0.001). In vivo antiproliferative effect of present formulation on immunodeficient female Balb/c mice showed ovarian tumor shrinkage from 2,920 to 143 mm(3) after 40 days. The present formulation of APTES-PEG-SPIO-based nanocomposite system of targeted drug delivery proved to be effective enough in order to treat deadly solid tumor of ovarian cancer in vitro and in vivo.
Subject(s)
Antineoplastic Agents/administration & dosage , Biocompatible Materials/chemistry , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Magnetite Nanoparticles/chemistry , Ovarian Neoplasms/drug therapy , Silanes/chemistry , Animals , Antineoplastic Agents/chemistry , Doxorubicin/chemistry , Drug Delivery Systems , Female , Humans , Mice , Mice, Inbred BALB C , Polyethylene Glycols/chemistry , PropylaminesABSTRACT
BACKGROUND: Genital tuberculosis is a common entity in gynecological practice particularly among infertile patients. It is rare in developed countries but is an important cause of infertility in developing countries. OBJECTIVE: The present study has investigated the prevalence of female genital tract tuberculosis (FGT) among infertile patients, which was conducted at the Obstetrics and Gynecology Unit-I, Allied Hospital, affiliated with Punjab Medical College, Faisalabad, Pakistan. MATERIALS AND METHODS: 150 infertile women who were referred to infertility clinic were selected randomly and enrolled in our study. Patients were scanned for possible presence of FGT by examination and relevant investigation. We evaluated various aspects (age, symptoms, signs, and socio-economic factors) of the patients having tuberculosis. RESULTS: Very high frequency of FGT (20%) was found among infertile patients. While, a total of 25 patients out of 30 (83.33%) showed primary infertility and the remaining 5 cases (16.67%) had secondary infertility. Among secondary infertility patients, the parity ranged between 1 and 2. A total of 40% of patients (12 cases) were asymptomatic but infertile. Evidence of family history was found in 4 out of a total of 30 patients (13.3%), respectively. According to histopathological and bacteriological examination of endometrial biopsy and laparotomy, tuberculous endometritis was found in 20 out of a total of 25 (80%) cases, while tuberculous salpingitis and tuberculous oophoritis were found both in 2 (8%) of the cases, respectively. Only one case (4%) of tuberculosis cervicitis was found in the present study. CONCLUSION: Although infertility is not a disease in classical sense, but it is an extremely important personal concern for many couples and a significant health problem for our profession. So, it is worthwhile to identify and evaluate the factors contributing to infertility.
