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Various environmental signals, such as temperature, pH, nutrient levels, salt content and the presence of other microorganisms, can influence biofilm’s development and dynamics. However, the innate mechanisms that govern at the molecular and cellular levels remain elusive. Here, we report the impact of physiologically relevant concentrations of NaCl on biofilm formation and the associated differences in an undomesticated natural isolate of Bacillus subtilis. NaCl exposure and its uptake by bacterial cells induced substantial changes in the architecture of pellicle biofilm and an upsurge in the expansion of biofilm colonies on agar surfaces. We have observed the upregulation of genes involved in motility and the downregulation of genes involved in the biosynthesis of extracellular matrix components through the transcription factor sigD, suggesting the possible underlying mechanisms. To further support these observations, we have used ΔsigD and ΔsrfAC null mutants, which showed compromised NaCl-induced effects. Our results indicate that NaCl induces a lifestyle shift in B. subtilis from a sessile biofilm state to an independent unicellular motile state. Overall, we present evidence that NaCl can reprogramme gene expression and alter cellular morphology and the state of cells to adapt to motility, which facilitates the expansion of bacterial colonies.

Emerging and reemerging fungal infections are very common in nosocomial and non-nosocomial settings in people having poor immunogenic profiles either due to hematopoietic stem cell transplants or are using immunomodulators to treat chronic inflammatory disease or autoimmune disorders, undergoing cancer therapy or suffering from an immune weakening disease like HIV. The refractory behavior of opportunistic fungi has necessitated the discovery of unconventional antifungals. The emergence of black fungus infection during COVID-19 also triggered the antifungal discovery program. Natural products are one of the alternative sources of antifungals. Endophytic fungi reside and co-evolve within their host plants and, therefore, offer a unique bioresource of novel chemical scaffolds with an array of bioactivities. Hence, immense possibilities exist that these unique chemical scaffolds expressed by the endophytic fungi may play a crucial role in overcoming the burgeoning antimicrobial resistance. These chemical scaffolds so expressed by these endophytic fungi comprise an array of chemical classes beginning from cyclic peptides, sesquiterpenoids, phenols, anthraquinones, coumarins, etc. In this study, endophytic fungi reported in the last six years (2018–2023) have been explored to document the antifungal entities they produce. Approximately 244 antifungal metabolites have been documented in this period by different groups of fungi existing as endophytes. Various aspects of these antifungal metabolites, such as antifungal potential and their chemical structures, have been presented. Yet another unique aspect of this review is the exploration of volatile antifungal compounds produced by these endophytic fungi. Further strategies like epigenetic modifications by chemical as well as biological methods and OSMAC to induce the silent gene clusters have also been presented to generate unprecedented bioactive compounds from these endophytic fungi.

Lung cancer is the leading cause of cancer-related mortality worldwide. Patients usually present at an advanced stage, so early diagnosis is important for better prognosis and management. Ultrasound-guided fine needle aspiration cytology (FNAC) is the diagnostic procedure of choice in lung lesions for timely diagnosis and better prognosis. Our study aimed to determine the specificity and sensitivity of FNAC in the diagnosis of pulmonary tumors and to assess the morphological features of various lung tumors. A retrospective study was carried out from June 2020 to August 2021 at a tertiary care center in Jabalpur, Madhya Pradesh, India. A total of 81 cases presenting with clinical and radiological features suggestive of lung malignancies were studied. Image-guided FNAC was done in all cases, and smears were stained using PAP and Giemsa stain. Typing was conducted on cytological evaluation, and histopathological correlation was obtained wherever possible. Immunohistochemistry was performed in a few cases where necessary. Eighty-one cases of ultrasound-guided FNAC of lung lesions were studied. Lung cancers were found to be more common in males, with a male-to-female ratio of 5.75:1, and the mean age at presentation was 55 years. Neoplastic lesions were 86.41%, and non-neoplastic lesions were 7.40%. Squamous cell carcinoma (60.49%) was found to be most common malignancy, followed by adenocarcinoma (11.11%) and small cell carcinoma (8.64%). Diagnostic specificity and sensitivity of FNAC were 100% and 95.65%, respectively. Image-guided FNAC is a safe, rapid, inexpensive, highly sensitive, and specific diagnostic procedure with fewer complications when performed by trained personnel. It helps in the early diagnosis and management of patients with pulmonary lesions leading to a better prognosis.

Synovial sarcoma is a rare malignant mesenchymal tumor that can develop at any anatomic site. Pulmonary sarcomas constitute 0.1–0.5% of all primary lung malignancies. Primary pulmonary synovial sarcoma is highly uncommon. Most of the patients present with large intrathoracic masses with complaints of cough, chest pain, shortness of breath, or hemoptysis. Multimodality treatment in the form of wide excision, chemotherapy, and radiotherapy is the mainstay of therapy. Synovial sarcoma is considered a high-grade tumor with a poor prognosis. We hereby present three cases of histologically proven synovial sarcoma with predominantly pulmonary involvement, along with their management and in hospital outcome.

Lymphadenopathy is a common but non-specific presentation of tuberculosis. Fine Needle Aspiration Cytology (FNAC) and Ziehl Neelsen (ZN) stain are preferred investigations of choice in evaluating lymphadenopathy. The aspirate obtained from FNAC may be used to perform a cartridge-based nucleic acid amplification test (CBNAAT). This study aimed to assess the efficacy of CBNAAT in the diagnosis of tubercular lymphadenopathy and to compare the CBNAAT and ZN stain microscopy results with FNAC findings. The study was conducted for a year at a tertiary referral center. FNAC was performed on 86 cases suspected of tubercular lymphadenitis. CBNAAT was performed on FNA material obtained from all these cases. Results of CBNAAT and ZN microscopy were compared with FNAC findings. CBNAAT was positive in 29 cases and ZN stain was positive in 15 cases. Out of 73 cases reported as tubercular lymphadenitis on FNAC, one case of reactive lymphoid hyperplasia and suppurative lymphadenitis was positive on the CBNAAT test. The sensitivity, specificity, and positive and negative predictive values of CBNAAT were 39.72%, 84.61%, 93.54%, and 20%, respectively. CBNAAT from FNA material can be used as an adjuvant diagnostic test in suspected tubercular lymphadenitis. However, CBNAAT cannot replace FNAC in the diagnosis of extra-pulmonary tuberculosis.

The characterization of Finsler spaces with Ricci curvature is an ancient and cumbersome one. In this paper, we have derived an expression of Ricci curvature for the homogeneous generalized Matsumoto change. Moreover, we have deduced the expression of Ricci curvature for the aforementioned space with vanishing the S-curvature. These findings contribute significantly to understanding the complex nature of Finsler spaces and their curvature properties.

Sarcoidosis is an idiopathic granulomatous disease and can virtually affect any organ system. Multiple factors, including tubercular antigens organic and environmental exposures, have been implicated in its pathogenesis. In addition to drugs, sarcoid-like reactions have been reported following varicella and influenza vaccination. Few reports of erythema nodosum and Lofgren syndrome have been reported after the COVID19 vaccination, though no histologic diagnosis was pursued in these cases. We herein report a case of sarcoidosis presenting with bilateral acute onset vision loss with a temporal association with COVID19 vaccination (ChadOx-1 n-COV, COVISHIELDTM). Symptoms started within two weeks of receiving the vaccine. Alternate causes for optic neuritis were excluded. Transbronchial lung biopsy showed the presence of non-caseating epithelioid cell granulomas. The patient received high-dose corticosteroids immediately after diagnosis, albeit with incomplete clinical improvement in vision on a three-month follow-up. In conclusion, we report a novel case of sarcoidosis-related optic neuritis following COVID19 vaccination.

Facial teratomas are uncommon tumours in children that distort the face and may be associated with functional problems. They are less common than cervical teratomas though they are often grouped together and considered an emergency due to their tendency to cause respiratory compromise. They tend to be large and cause cosmetic issues; hence usually noticed early and medical help sought promptly by parents. The close proximity of facial teratomas to structures like eyes, parotid gland, facial nerve, vessels and brain makes them challenging and requires a patient and meticulous exploration during surgery. We present a case of an 11 month old girl with left sided temporal teratoma. Well planning of the incision and complete excision of the tumour with careful sparing of the facial nerves and parotid gland yielded good result.

Wooden foreign body (WFB) injuries in children are common. They may report with acute presentation or be delayed as retained foreign body giving rise to complications. Cases with superficial skin penetration by these foreign bodies and acute presentation may be convenient to diagnose and remove. However, localising deeply impacted and chronically retained WFB is challenging, as they are usually not radiopaque and have a tendency to move deeper into the surrounding soft tissues with time. Foreign body retained for prolonged duration may present with either cellulitis, deep tissue infections, sinus, restriction of joint movements, necrotising fasciitis, osteomyelitis or tumour-like mass. We present an 8-year-old boy with discharging sinuses in the right iliac fossa and medial aspect of the right upper thigh, due to an impacted WFB for 3 months. Prompt radiological imaging and surgical removal helped him recover completely.

Background: Coronavirus disease Pandemic has affected the health-care delivery at all institutions worldwide. Analysis of multi-institutional data would reflect the impact and challenges of this pandemic in managing pediatric surgical cases. To assess the impact of lockdown due to coronavirus disease 2019 (COVID-19) on the pediatric surgical cases operated at four tertiary care institutions. Materials and Methods: Retrospective data of all patients operated at four tertiary care centers in North India in three different states during the imposition of lockdown due to COVID-19 were collected and compared to the immediate prelockdown period. The impact of following the guidelines for surgery during this period was studied. Results: All the institutions involved in the study showed a significant fall in the number and nature of patients treated during the lockdown period when compared to the prelockdown data. No elective cases were operated; 100 children were operated during this period of which neonates (56%) formed the major group; most of them were cases of congenital anomalies which could not be deferred; solid tumours (3/100) were operated on semi-emergency basis; number of trauma patients fell down drastically (1/100); one patient had bronchoscopic foreign body removal; other patients were operated for different causes of acute abdomen. Several measures in the outpatient, intraoperative, and in-patient care were adopted to lessen the spread of virus to the patient and health-care team. Conclusion: Corona pandemic severely impacted both the number and types of patients operated. Strict adherence to the protocol delayed emergency treatment and increased the cost of definitive management.

Curcumin is a well-recognized antioxidant phytoactive isolated from the rhizomes of Curcuma longa. Numerous landmark investigations have proved the antioxidant and hepatoprotective potential of curcumin. The aim of present study was to target curcumin loaded nanocarriers to hepatocytes using asialoglycoprotein receptors targeting strategy. Mannose, a water-soluble carbohydrate, was hydrophobized by anchoring stearylamine with an objective to conjugate mannose on the surface of curcumin loaded nanostructured lipid carriers for targeting asialoglycoprotein receptors on hepatocytes. Mannose conjugated stearylamine was synthesized and characterized using various analytical techniques. The synthesized targeting ligand was incorporated curcumin loaded nanostructured lipid carriers and characterized by photon correlation spectroscopy. Zeta potential measurement was used to confirm the conjugation of the synthesized ligand to the surface of drug-loaded nanostructured lipid carriers. CCl4 induced hepatotoxicity in male Wistar rats was used as an experimental animal model to evaluate the hepatoprotective potential of formulated drug encapsulated nanostructured lipid carriers. The hepatoprotective potential was assessed by measuring serum liver injury markers and oxidative stress parameters in the liver post–mitochondrial supernatant. Mannose conjugated nanostructured lipid carriers showed acceptable particle size which revealed its suitability for hepatocyte targeting. In addition to this, mannose conjugated nanocarriers revealed significantly better (p ​

Langerhans cell histiocytosis is an uncommon disease of childhood. Intrathoracic transposition flaps have been described for a management of number of conditions. We discuss our experience of the use of serratus anterior flap for the obliteration of a pulmonary bulla with a communicating airway, in a 1½-year-old pediatric patient with multisystem Langerhans cell histiocytosis who presented with recurrent pneumothorax with empyema due to rupture of bullae.

Background: Overexposure to sunlight and high UV radiation leads to uncontrolled melanin production in the skin, leading to hyperpigmentation and inflammatory diseases. Therefore, there is a need to discover safe and highly prospective drugs from natural sources. Previous studies have shown that leaves and rhizome extract of Alpinia nigra possesses antioxidant and anti-inflammatory activities. Among the components of the most bioactive methanol and ethyl acetate extract, flavones seem to be the most promising compound. Aim: To evaluate the antioxidant, anti-tyrosinase and anti-inflammatory efficacy of 3,5-dihydroxy-4′,7-dimethoxyflavone (DHDM). Methods: The flavone DHDM was isolated from A. nigra ethyl acetate leaf extract and characterized by multi spectroscopic techniques. The toxicity of DHDM was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The antioxidant and reactive oxygen species (ROS) inhibitory activity were determined by 2,2-Diphenyl-1-picrylhydrazy (DPPH) assay and by flow cytometry. Further, the anti-tyrosinase activity was evaluated by in silico (molecular docking), fluorescence, and enzyme kinetics studies. The anti-inflammatory activity was demonstrated by western blotting. Results: The cell viability assay with DHDM showed no inhibition at ≤200 µM concentration in THP-1 (human macrophage) and ≤80 µM in HaCaT (human keratinocyte) cell lines. Additionally, strong antioxidant properties and reduced ROS generation suggested prevention from oxidative damage and skin aging. Strong binding of DHDM to tyrosinase leading to the conformational change was revealed by fluorescence quenching studies and molecular docking. Further, the anti-tyrosinase activity of the isolated compound was observed at 42.5 µM (IC50). Moreover, DHDM inhibited the expression of anti-inflammatory proteins like TNF-α and NF-κB. Conclusion: The DHDM demonstrates the efficient antioxidant, anti-tyrosinase and anti-inflammatory potential, which could be developed for obtaining a new drug for the management of hyperpigmentation and inflammatory-related diseases.

Soft tissue tumors are not uncommon in childhood and comprise entities that range from common to very rare malignancies. Infantile fibrosarcoma (IFS) is a rare pediatric malignancy mainly seen in the first two years of life. The data about the incidence of infantile fibrosarcoma occurring in the neck in the Indian subcontinent is scarce. To the best of our knowledge, only one case of infant cervical IFS has been reported previously in the Indian subcontinent. We present another case of an eight-year-old male patient with a rapidly growing mass on the left side of the neck. He was successfully treated with a combined modality of surgery and chemotherapy with a good outcome. Among the soft tissue tumors of childhood, IFS is a rare entity. It has a good prognosis and lesser chance of distant metastasis as compared to adult fibrosarcoma. Though surgical excision is the mainstay of treatment, chemotherapy also has a significant role in the treatment of primary tumor and metastasis. We discuss the stated case to bring to the notice this uncommon cause, which can be considered as a differential diagnosis of upper cervical swellings. A better understanding of this entity would help in early diagnosis and aggressive treatment, reducing the overall morbidity and mortality.

Acute appendicitis is a quite common condition in children, but it is very less common in neonates and infants. Acute appendicitis has several ways of presentations but its presentation as mechanical obstruction is very rare. We report a case of a 16 days old male patients who presented with acute intestinal obstruction due to appendicular band syndrome, and had been treated successfully in our institute

Prune belly syndrome is an extremely rare congenital condition occurring predominantly in males. This triad syndrome comprises of partial or complete deficient abdominal wall muscles, undescended testes and dilated urinary collecting system. We present the case of a 2-year-old male patient, who presented with classic prune belly syndrome, operated with modification in classical Monfort technique of abdominoplasty. The basis of this approach was to save and use the supraumbilical abdominal wall which has better tensile strength. The infraumbilical skin was mostly discarded. The outcome was better in terms of cosmetic appearance as the scar was limited to the lower abdomen and better anterior abdominal wall strength.

Background: Annular pancreas is an uncommon cause of duodenal obstruction and rarely causes complete duodenal obstruction. Due to its rarity of identification in the antenatal period and overlapping imaging features with other causes of duodenal obstruction; it is often misdiagnosed. Case presentation: A 33-year-old primigravida came for routine antenatal ultrasonography at 28 weeks and 4 days of gestational age. On antenatal ultrasonography, dilated duodenum and stomach were seen giving a double bubble sign and a hyperechoic band surrounding the duodenum. Associated polyhydramnios was also present. Fetal MRI was also done. Postpartum ultrasonography demonstrated pancreatic tissue surrounding the duodenum. The upper gastrointestinal contrast study showed a non-passage of contrast beyond the second part of the duodenum. Due to symptoms of obstruction, the neonate was operated on, and the underlying cause was found to be the annular pancreas. Conclusion: Diagnosis of duodenal obstruction due to the annular pancreas is very important in the antenatal period to plan for appropriate therapeutic interventions after birth. A double bubble sign is seen due to various etiologies however the presence of a hyperechoic band in the antenatal ultrasound may point to the diagnosis of the annular pancreas.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an extremely contagious disease whereby the virus damages the host’s respiratory tract via entering through the ACE2 receptor. Cardiovascular disorder is being recognized in the majority of COVID-19 patients; yet, the relationship between SARS-CoV-2 and heart failure has not been established. In the present study, SARS-CoV-2 infection was induced in the monkey model. Thereafter, heart tissue samples were collected, and pathological changes were analyzed in the left ventricular tissue by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to T lymphocytes and macrophages. The findings revealed that SARS-CoV-2 infection induces several pathological changes in the heart, which cause cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells, and hypertrophy. Furthermore, collagen-specific staining showed the development of cardiac fibrosis in the interstitial and perivascular regions in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. These findings suggest the progression of the disease, which can lead to the development of severe complications, including heart failure. Additionally, SARS-CoV-2 antigen staining detected the presence of virus particles in the myocardium. Thus, we found that SARS-CoV-2 infection is characterized by an exaggerated inflammatory immune response in the heart, which possibly contributes to myocardial remodeling and subsequent fibrosis.

Antibiotic resistance is becoming a burning issue due to the frequent use of antibiotics for curing common bacterial infections, indicating that we are running out of effective antibiotics. This has been more obvious during recent corona pandemics. Similarly, enhancement of antimicrobial resistance (AMR) is strengthening the pathogenicity and virulence of infectious microbes. Endophytes have shown expression of various new many bioactive compounds with significant biological activities. Specifically, in endophytic fungi, bioactive metabolites with unique skeletons have been identified which could be helpful in the prevention of increasing antimicrobial resistance. The major classes of metabolites reported include anthraquinone, sesquiterpenoid, chromone, xanthone, phenols, quinones, quinolone, piperazine, coumarins and cyclic peptides. In the present review, we reported 451 bioactive metabolites isolated from various groups of endophytic fungi from January 2015 to April 2021 along with their antibacterial profiling, chemical structures and mode of action. In addition, we also discussed various methods including epigenetic modifications, co-culture, and OSMAC to induce silent gene clusters for the production of noble bioactive compounds in endophytic fungi.

Aim and Objectives: Despite the significant advancements in the management of anorectal malformations (ARMs), there are various surgical and functional complications reported. Complications are closely related with the surgical techniques adopted and the types of malformations. In this article, we present our experiences with ARM patients who required reoperation after unsuccessful previous surgeries or who had developed complications related to the previous surgical techniques. Materials and Methods: We retrospectively reviewed clinical and electronic records of all the patients with ARM who were operated for ARMs in our institute from June 2010 to May 2016. All ARM patients who needed reoperation were included in the study. These patients were previously operated outside our institute and referred to us with ongoing problems of constipation, stool impaction with overflow incontinence, perineal soiling, and difficult urination. Results: There were 31 patients (M:F = 2.1:1) of ARM, reoperated for 38 indications during the above-mentioned period. Five patients had more than one problem. Presentation included neoanal stenosis (11), complete obliteration of neoanus (2), malpositioned neoanus (2), persistent/recurrent rectourethral fistula (3), iatrogenic rectovaginal fistula (4), rectal prolapse (5), large widened neoanus with soiling (2), and urethral stricture (2), which required revision interventions. Six patients had megarectum. All patients showed improvement in their symptoms after revision surgery, but 10 (41.7%) patients required further regular bowel management program (BMP) to avoid the soiling and constipation. Fourteen (58.3%) patients stayed clean without regular BMP. Conclusion: All these complications had clear explanations and are well described in the literature. Revision surgery in such patients had fair outcome, but some sort of BMP was required. Both posterior sagittal anorectoplasty and anterior sagittal anorectoplasty are excellent techniques for revision surgery with few simple modifications.

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.

Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of approximately 10% and a 5-year survival rate of

The true hermaphroditism represents only 5% of all disorders of sexual differentiation, thus it is one of the rarest varieties. Diagnosis of true hermaphroditism requires the presence of both ovary and testis either as separate organs or combined to form unilateral or bilateral ovotestis. Dysgerminoma is one of the tumours which are commonly seen in true hermaphrodites. The main treatment modality includes removal of the dysgerminoma followed by chemotherapy if the tumour is Ib-IV stage So, early diagnosis of hermaphrodite and associated tumours can help the patient to lead a better life ahead as enlarged tumours have more aggressive treatment and are associated with poor prognosis. We are presenting this case because true hermaphrodites are themselves rare, and association with germ cell tumours is still rarer. This case is still special as the diagnosis of true hermaphrodite was made during surgery only.

The efficacy of a drug in a specific application requires the maintenance of appropriate drug blood level concentration during a prolonged period of time. Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. The objective of this work is to prepare and evaluate diltiazem HCl loaded albumin microparticles using a factorial design. Albumin (natural polymer) microparticles were prepared by emulsion heat-stabilization method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance for entrapment efficiency indicates that entrapment efficiency is best fitted to a response surface linear model. Surface morphology was studied by scanning electron microscopy. Scanning electron microscopy of the microparticles revealed a spherical, nonporous and uniform appearance, with a smooth surface. The geometric mean diameter of the microparticles was found to be 2-9 µm, which more than 75% were below 3.5 µm and drug incorporation efficiency of 59.74 to 72.48% (w/w). In vitro release profile for formulations containing diltiazem HCl loaded BSA microparticles with heat stabilization technique shows slow controlled the release of the drug up to 24 hours. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microparticles exhibited a prolonged release for almost 24 hours. On comparing regression-coefficient (r²) values for Hixson Crowel, Higuchi and Peppas kinetic models, different batches of microparticles showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D:P ratio. From the statistical analysis it was observed that as the drug:polymer (D:P) ratio increased, there was a significant increase in the encapsulation efficiency. Based on the particle size, entrapment efficiency and physical appearance, DTM-3 formulations were selected for in vivo release study and stability study. The in vivo result of drug loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 ºC. In present study, diltiazem HCl loaded BSA microparticles were prepared and targeted to various organs to satisfactory level and were found to be stable at 4 ºC.A eficácia terapêutica de um fármaco depende da manutenção de seu nível plasmático adequado em determinado intervalo de tempo. Nesse sentido, a liberação modificada de fármacos está disponível em muitas vias de administração e oferece muitas vantagens (como micropartículas e nanopartículas) quando comparada às formulações de liberação imediata. Essas vantagens incluem reduzida frequência da dosagem, melhor controle terapêutico e menos efeitos colaterais. Assim sendo, esses produtos apresentam maior aceitação pelos pacientes. Os avanços na ciência dos materiais, na engenharia das partículas, em manufatura e em nanotecnologia permitiram a introdução no mercado de vários produtos de liberação modificada e vários outros se encontram em desenvolvimento pré-clínico e clínico. O objetivo do presente trabalho foi preparar e avaliar o fármaco cloridrato de diltiazem associado a micropartículas de albumina utilizando planejamento fatorial. As micropartículas de albumina, um polímero natural, foram preparadas por método de emulsão empregando estabilização por calor. As formulações selecionadas foram caracterizadas no que se refere à sua eficiência de encapsulamento, tamanho médio de partículas, morfologia de superfície e perfil de liberação do fármaco. A análise de variância relativa à eficiência de encapsulamento indicou superfície de resposta linear. Com referência à morfologia superficial, essa foi avaliada empregando microscopia eletrônica de varredura. Essa análise revelou micropartículas esféricas, não porosas e de aparência uniforme, com superfície lisa. O diâmetro médio das micropartículas foi entre 2 e 9 µm, sendo que mais de 75% das micropartículas se apresentaram abaixo de 3,5 µm. Além disso, a eficiência de encapsulamento foi entre 59,74 e 72,48%. Quanto ao ensaio para avaliação do perfil de liberação in vitro do fármaco associado às micropartículas, as formulações apresentaram liberação lenta até 24 horas. O comportamento foi caracterizado por liberação inicial (efeito burst) seguida por liberação lenta. Todas as fórmulas selecionadas apresentaram liberação prolongada por aproximadamente 24 horas. Na comparação entre os valores de coeficientes de regressão (R²), os modelos propostos por Hixson Crowel, Higuchi e Peppas, para diferentes formulações de micropartículas, demonstraram cinética de liberação de acordo com modelo Fickiano e não-Fickiano. O mecanismo de liberação do fármaco foi regulado pela razão entre o fármaco e o polímero. A análise estatística revelou significativo aumento da eficiência de encapsulamento quando essa razão aumentou. As avaliações relativas à análise dimensional das micropartículas, à eficiência de encapsulamento do fármaco e à morfologia permitiram a seleção da formulação DTM-3 para os ensaios de liberação in vivo e para o estudo da estabilidade. O ensaio de liberação in vivo do fármaco associado às micropartículas demonstrou sítio-alvo preferencial no fígado, seguido pelos pulmões rins e baço. No presente estudo, as micropartículas de albumina contendo cloridrato de diltiazem foram adequadamente preparadas e orientadas satisfatoriamente para vários órgãos. Além disso, a formulação selecionada apresentou estabilidade físico-química a 4 ºC.