Effects of diabetes mellitus on retreatment of Tuberculosis: A multi-centered case-control study from Bangladesh.

Objectives: Several studies suggested that diabetes mellitus (DM) worsens the tuberculosis (TB) treatment outcome. But information regarding the association of DM with retreatment of TB is very scarce in Bangladesh. Present study aimed to assess the effects of DM on retreatment of TB. Methods: This case-control study was conducted among 254 patients (127 cases and 127 controls) from January 2022 - December 2022. Patients were recruited by purposive sampling from 92 centers of the Diabetic Association of Bangladesh (BADAS). Data were collected by face-to-face interview and record reviewing with the help of semi-structured questionnaire and checklist respectively. Quality of data was maintained in all stages of the study. Data were analyzed by using IBM SPSS software. Informed written consent was taken from each patient prior to the study. Ethical issues were maintained strictly. Results: Present study matched the age and sex of cases and controls. The study revealed that majority of case (89.0) and controls (97.6) were married. Among cases 78.0 % had DM and among controls 64.6 % had DM. Among diabetic patients, 78.8 % cases' and 64.6 % controls' HbA1C level was not within normal range. The study found that, the number of episodes of previous TB (AOR = 3.088, ρ = 0.019), presence of DM (AOR = 2.817, ρ = 0.012) and uncontrolled HbA1C level (AOR = 2.500, ρ = 0.028) were independently associated with retreatment of TB. Conclusion: The study found that presence of DM, uncontrolled HbA1C level and multiple episodes of previous TB were the risk factors for retreatment of TB. So, a separate guideline for treatment of TB-DM patients should be established to prevent retreatment cases.

The Epidemiology of Melioidosis and Its Association with Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Melioidosis is an under-recognized fatal disease in humans, caused by the Gram-negative bacterium Burkholderia pseudomallei. Globally, more than 35,000 human melioidosis cases have been reported since 1911. Soil acts as the natural reservoir of B. pseudomallei. Humans may become infected by this pathogen through direct contact with contaminated soil and/or water. Melioidosis commonly occurs in patients with diabetes mellitus, who increase the occurrence of melioidosis in a population. We carried out a systematic review and meta-analysis to investigate to what extent diabetes mellitus affects the patient in getting melioidosis. We selected 39 articles for meta-analysis. This extensive review also provided the latest updates on the global distribution, clinical manifestation, preexisting underlying diseases, and risk factors of melioidosis. Diabetes mellitus was identified as the predominant predisposing factor for melioidosis in humans. The overall proportion of melioidosis cases having diabetes was 45.68% (95% CI: 44.8-46.57, p < 0.001). Patients with diabetes mellitus were three times more likely to develop melioidosis than patients with no diabetes (RR 3.40, 95% CI: 2.92-3.87, p < 0.001). The other potential risk factors included old age, exposure to soil and water, preexisting underlying diseases (chronic kidney disease, lung disease, heart disease, and thalassemia), and agricultural activities. Evidence-based clinical practice guidelines for melioidosis in patients with diabetes mellitus may be developed and shared with healthcare professionals of melioidosis endemic countries to reduce morbidity.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin.

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08-206.4 ± 2.26 nm, zeta potential was -17.8 ± 1.26 to -24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

Micro and nanorobot-based drug delivery: an overview.

Progress in the drug delivery system in the last few decades has led to many advancements for efficient drug delivery. Both micro and nanorobots, are regarded as superior drug delivery systems to deliver drugs efficiently by altering other forms of energy into propulsion and movements. Furthermore, it can be advantageous as it is directed to targeted sites beneath physiological environments and conditions. They have been validated to possess the capability to encapsulate, transport, and supply therapeutic contents directly to the disease sites, thus enhancing the therapeutic efficiency and decreasing systemic side effects of the toxic drugs. This review discusses about the microand nanorobots for the diagnostics and management of diseases, types of micro, and nanorobots, role of robots in drug delivery, and its biomedical applications.

Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein.

The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced in vitro dissolution. Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45-762.8±2.05 nm and -22.4±0.55-31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier (Maltodextrin) followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.

Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma.

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81-187.13 ± 4.15 nm), colloidal stability (-13.27 ± 0.04 to -32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01-79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer-Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer efficacy.

AIMS: The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line. MATERIALS AND METHODS: The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells. SIGNIFICANT FINDINGS: Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents. SIGNIFICANCE: The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.

Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy.

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization.

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50-148µm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.

Emphysematous pyelonephritis: experience at a tertiary care hospital in Bangladesh.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the renal parenchyma, collecting system and/or perinephric tissues, characterized by gas accumulation. We describe clinical, laboratory and imaging characteristics and in-hospital outcomes of patients with EPN. METHODS: This retrospective observational study was carried out at BIRDEM General Hospital, Dhaka, Bangladesh between 2014 and 2020. RESULTS: We followed 20 patients (mean age 49.4 years; females 70%). Risk factors for EPN were diabetes mellitus (in 100%) and renal stones (in 10%). Fever, loin pain, vomiting and dysuria were common. Complications included acute kidney injury (AKI, 70%; mostly stage 1, 78.6%), hyponatraemia (55%) and bacteraemia (15%). Escherichia coli was the most common (60%) urinary isolate. Most patients (80%) had class 2 EPN, with 15% class 3B and 5% class 3A. Besides medical management, four (20%) required surgery (nephrectomy in 3). Nephrectomised patients had a higher radiological class (p = 0.032) and incidence of AKI (p = 0.034). No deaths occurred. CONCLUSION: EPN occurred predominantly in female diabetic patients, who presented with fever, loin pain, vomiting and dysuria. Two-thirds of patients had AKI and one-fifth required surgery, and there were no deaths.

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting.

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

Class 4 emphysematous pyelonephritis with emphysematous cystitis: report of a rare case from Bangladesh.

Emphysematous pyelonephritis is a rare, severe form of necrotising infection of the kidneys and peri-nephric tissues with gas accumulation, occurring predominantly among patients with diabetes mellitus. Computed tomography scan can identify the distribution of gas in the affected reno-ureteral units and so establish and classify the diagnosis. We report a case of class 4 emphysematous pyelonephritis with emphysematous cystitis, occurring in a young Bangladeshi male, who presented with features of upper urinary tract infection. He had a background history of fibro-calculous pancreatic diabetes and chronic kidney disease. Imaging also revealed renal stones. He responded to conservative treatment.

In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.

AIMS: The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. MATERIALS AND METHODS: Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. KEY FINDINGS: A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. SIGNIFICANCE: The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.

Microfluidic fabrication and characterization of Sorafenib-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery.

Lipid polymer hybrid nanoparticles (LPHNPs) have been merged as potential nanocarriers for treatment of cancer. In the present study, LPHNPs loaded with Sorafenib (SFN) were prepared with PLGA, Lecithin and DSPE-PEG 2000 by using the bulk nanoprecipitation and microfluidic (MF) co-flow nanoprecipitation techniques. Herein, a glass capillary microfluidic device was primed to optimize the LPHNPs and compared to the bulk nanoprecipitation method. The morphological analysis of prepared LPHNPs revealed the well-defined spherical nano-sized particles in bulk nanoprecipitation method. Whereas, core shell morphology was observed in the MF method. The formulation prepared by the MF method (MF1-MF3) indicated relatively higher % EE (95.0%, 93.8% and 88.7%) and controlled release of the SFN from the particles as compared to the LPHNPs obtained by the bulk nanoprecipitation method. However, the release of SFN from all LPHNP formulation followed Higuchi model (R2 = 0.9901-0.9389) with Fickian diffusion mechanism. Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and powder X-rays diffraction (pXRD) studies depicted the compatibility of SFN with all the structural components. In addition, the colloidal stability, in vitro cytotoxicity and cell growth inhibition studies of LPHNPs also demonstrated stability in biological media, biocompatibility and safety with enhanced anti-proliferative effects than the free SFN in breast cancer and prostate cancer cells. In conclusion, LPHNPs provided a prospective platform for the cancer chemotherapy and substantially improved the knowledge of fabrication and optimization of the hybrid nanoparticles.

Histoplasmosis: An Emerging or Neglected Disease in Bangladesh? A Systematic Review.

Histoplasmosis is uncommon in many parts of the world, including Bangladesh, where, in recent years, cases are increasingly reported. We sought to describe the sociodemographic characteristics, clinical presentation, investigations, treatment, and outcome of histoplasmosis in Bangladesh. We conducted a retrospective data review of published literature from 1962 to 2017, containing information on histoplasmosis in and/or from Bangladesh. Unpublished, well-documented histoplasmosis cases were also included. A total of 26 male patients aged 8-75 years, with a diagnosis of histoplasmosis were included; nine were farmers, seven had diabetes, one was a renal transplant recipient, and four had HIV/AIDS. Fever (n = 20), weight loss (n = 17), anemia (n = 15), lymphadenopathy (n = 9), and hepatosplenomegaly (n = 7) were common. Eleven patients had bilateral adrenal enlargement. Diagnosis was confirmed by histo/cytopathology from skin (n = 1), oropharyngeal ulcers (n = 8), lymph nodes (n = 3), adrenal glands (n = 11), paravertebral soft tissue (n = 2), and bone marrow (n = 4). Cultures of representative samples and antibodies were detected in three and two cases, respectively. Twenty-two patients had disseminated histoplasmosis and four patients had localized oropharyngeal disease. Nine patients were prescribed anti-tuberculosis drugs empirically before establishing the diagnosis of histoplasmosis. Treatment consisted of amphotericin B and itraconazole. Six patients died in hospital, 14 patients recovered with relapse in two cases, and the outcome of the other patients could not be ascertained. Histoplasmosis is thought to be endemic in Bangladesh, but few cases are reported to date, which may be due to many asymptomatic, undiagnosed, misdiagnosed, or under-reported cases. Histoplasmosis should be considered as a differential in appropriate clinical scenarios.

Septicemic melioidosis complicating undiagnosed chronic kidney disease and beta-thalassemia minor in a Bangladeshi farmer.

Melioidosis is an emerging infectious disease in many countries including Bangladesh. Patients with diabetes mellitus are at increased risk for infection by Burkholderia pseudomallei, the causative agent for melioidosis. Here, we report an autochthonous case of septicemic melioidosis occurring in a middle-aged non-diabetic Bangladeshi farmer who presented with prolonged pyrexia and splenomegaly. Diagnostic workup revealed splenic micro-abscesses, previously undetected chronic kidney disease (CKD) and beta-thalassemia minor. This case stresses the importance of searching for less common risk factors for melioidosis such as CKD and hemolytic anemia.

Libman-Sacks endocarditis in a Bangladeshi patient suffering from rhupus.

Libman-Sacks endocarditis (LSE) is one of the most characteristic cardiac lesions in systemic lupus erythematosus (SLE). Patients may remain asymptomatic, while symptomatic patients often suffer with systemic emboli. These commonly test positive for anti-phospholipid antibody (aPA). The association of LSE with an overlap of rheumatoid arthritis (RA) and lupus (also known as 'rhupus') is rare. We report such a patient, who had been diagnosed as having RA seven years before and had suffered an acute ischaemic stroke one year previously and had echocardiographic evidence of LSE found during routine evaluation. However, she tested negative for aPA.

Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation.

INTRODUCTION: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel. METHODS: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats. RESULTS AND DISCUSSION: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm-479.65 nm), and zeta potential (30.45-35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57-69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2 = 0.9734-0.9786, n= 0.264-0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs. CONCLUSION: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.