Sameer Vyas

Liposomes modified with cyclic RGD peptide for tumor targeting.

Cyclic RGD peptide anchored sterically stabilized liposomes (RGD-SL) were investigated for selective and preferential presentation of carrier contents at angiogenic endothelial cells overexpressing αvβ3 integrins on and around tumor tissue and thus for assessing their targetabilty. Liposomes were prepared using distearoylphosphatidylcholine (DSPC), cholesterol and distearoylphosphatidylethanolamine–polyethyleneglycol–RGD peptide conjugate (DSPE–PEG–RGD) in a molar ratio 56:39:5. The control RAD peptide anchored sterically stabilized liposomes (RAD-SL) and liposome with 5 mol% PEG (SL) without peptide conjugate which had similar lipid composition were used for comparison. The average size of all liposome preparations prepared was approximately 105 nm and maximum drug entrapment was 10.2±1.1%. In vitro endothelial cell binding of liposomes exhibited 7-fold higher binding of RGD-SL to HUVEC in comparison to the SL and RAD-SL. Spontaneous lung metastasis and angiogenesis assays show that RGD peptide anchored liposomes are significantly (p<0.01) effective in the prevention of lung metastasis and angiogenesis compared to free 5-FU, SL and RAD-SL. In therapeutic experiments, 5-FU, SL, RGD-SL and RAD-SL were administered intravenously on day 4 at the dose of 10 mg 5-FU/kg body weight to B16F10 tumor bearing BALB/c mice resulting in effective regression of tumors compared with free 5-FU, SL and RAD-SL. Results indicate that cyclic RGD peptide anchored sterically stabilized liposomes bearing 5-FU are significantly (p<0.01) active against primary tumor and metastasis than the non-targeted sterically stabilized liposomes and free drug. Thus cyclic RGD peptide anchored sterically stabilized liposomes hold potential of targeted cancer chemotherapeutics.

Chitosan nanoparticles encapsulated vesicular systems for oral immunization: preparation, in‐vitro and in‐vivo characterization

BSA‐loaded chitosan nanoparticles were prepared and encapsulated in vesicles (liposomes and nio‐somes) to make them acid resistant upon oral administration. Prepared systems were characterized in‐vitro for shape, size, entrapment efficiency and stability in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The immune stimulating activity was studied by measuring serum IgG titre and secretory IgA (sIgA) levels in mucosal secretions following oral administration of various formulations in albino rats. Significantly higher (P < 0.05) serum IgG titres were achieved following oral administration of novel nanoparticulate vesicular formulations as compared with unmodified chitosan nanoparticles. Further, high sIgA levels in mucosal secretions advocated a possible application of chitosan nanoparticle encapsulated in vesicles as an oral vaccine delivery carrier‐adjuvant system.

Mannosylated Niosomes as Adjuvant-Carrier System for Oral Mucosal Immunization

The aim of the present study was to develop mannosylated niosomes as oral vaccine delivery carrier and adjuvant for the induction of humoral, cellular, and mucosal immunity. Tetanus toxoid (TT) loaded niosomes composed of sorbiton monostearate (Span 60), cholesterol, and stearylamine were prepared by the reverse-phase evaporation method. They were coated with a modified polysaccharide o-palmitoyl mannan (OPM) to protect them from bile salts caused dissolution and enzymatic degradation in the gastrointestinal tract and to enhance their affinity toward the antigen presenting cells of Peyers patches. Prepared niosomes were characterized in vitro for their size, shape, entrapment efficiency, ligand binding specificity, and stability in simulated gastric fluid and simulated intestinal fluid. OPM-coated niosomes were found to more stable in simulated gastrointestinal conditions. The immune stimulating activity was studied by measuring serum IgG titer, IgG2a/IgG1 ratio in serum, and sIgA levels in intestinal and salivary secretions following oral administration of niosomal formulations in albino rats. The results were compared with alum-adsorbed TT following oral and intramuscular administration, and it was observed that OPM-coated niosomes produced better IgG levels as compared to plain uncoated niosomes and alum-adsorbed TT upon oral administration. Oral niosomes also elicited a significant mucosal immune response (sIgA levels in mucosal secretions). The developed formulations also elicited a combined serum IgG2a/IgG1 response, suggesting that they were capable of eliciting both humoral and cellular response. The study signifies the potential of OPM-coated niosomes as an oral vaccine delivery carrier and adjuvant. The proposed system is simple, stable, and cost-effective and may be clinically acceptable.

Mannosylated niosomes as carrier adjuvant system for topical immunization

The aim of this study was to develop mannosylated niosomes as a topical vaccine delivery carrier and adjuvant for the induction of both humoral and cellular immunity. Bovine serum albumin (BSA)‐loaded niosomes composed of sorbitan monostearate/sorbitan trioleate (Span 60/Span 85), cholesterol and stearylamine as constitutive lipids were prepared by the reverse‐phase evaporation method. The niosomes were coated with a modified polysaccharide O‐palmitoyl mannan (OPM) to target them to Langerhans cells, the major antigen presenting cells found in abundance beneath the stratum corneum. Prepared niosomes were characterized in‐vitro for their size, shape, entrapment efficiency and ligand binding specificity. The immune stimulating activity was studied by measuring serum IgG titre and its subclasses (IgG2a/IgG1 ratio) following topical application of various niosomal formulations in albino rats. The results were compared with alum‐adsorbed BSA following topical application and intramuscular injection. It was observed that niosomal formulations elicited a significantly higher serum IgG titre upon topical application as compared with topically applied alum adsorbed BSA (P<0.05). The serum IgG levels were significantly higher for the mannosylated niosomes as compared with plain uncoated niosomes (P<0.05). All formulations displayed a combined serum IgG2a/IgG1 response, which suggested that the formulations were capable of eliciting both humoral and cellular responses. The study signified the potential of OPM‐coated niosomes as a topical vaccine delivery carrier and adjuvant. The proposed system would be simple, stable, and cost effective and might be clinically acceptable.

Spontaneous perforation of pyometra in a cervical cancer patient: a case report and literature review

Abstract Pyometra is an uncommon condition with an incidence of less than 1% in gynaecologic patients. Spontaneous rupture of pyometra in cervical cancer presenting as generalized peritonitis is very rare. Only four cases have been described in the English literature to the best of our knowledge and from a PubMed search. The index case is an elderly postmenopausal female who was diagnosed with cervical cancer, started on radiotherapy and presented with features of generalized peritonitis. Contrast-enhanced CT revealed uterine perforation at the fundus with multiple abdominal and pelvic collections. A brief review of all the cases of ruptured pyometra in cervical cancer in the literature and a discussion of the role of imaging is presented.

Hepatic arteriovenous fistulae: role of interventional radiology.

IntroductionHepatic arterial venous fistulae are abnormal communications between the hepatic artery and portal or hepatic vein and commonly occur either secondary to iatrogenic causes like liver biopsy, transhepatic biliary drainage, transhepatic cholangiogram and surgery, or following mechanical insult like blunt or penetrating trauma. Congenital fistulae are rare. Treatment is warranted as an emergency management or in the development of portal hypertension/heart failure in chronic cases. Both surgical and endovascular occlusion of the fistula can be attempted with the latter carrying low intra and post-procedure morbidity. Endovascular treatment has thus currently emerged as a minimally invasive reliable treatment option in such individuals.Methods and ResultsWe describe a short series consisting of four cases of acquired hepatic arterioportal/venous fistulae, which were referred to interventional radiology for endovascular management over the last 2 years. Three patients had arterio-portal communication and one patient had communication between the hepatic artery and middle hepatic vein. Successful embolization through the transarterial route was achieved in all four patients. A brief discussion of these cases is presented along with a relevant review of literature.ConclusionsEndovascular techniques currently form less invasive and first line treatment options in arterioportal/venous fistulae, surgery being reserved only for unsuccessful embolizations/complex fistulae.

Liposomes modified with YIGSR peptide for tumor targeting

YIGSR peptide anchored sterically stabilized liposomes (YIGSR-SL) were investigated for selective and preferential presentation of carrier contents at angiogenic endothelial cells overexpressing laminin receptors on and around tumor tissue and thus for assessing their targetabilty. In vitro endothelial cell binding of liposomes exhibited 7-fold higher binding of YIGSR-SL to HUVEC in comparison to the nontargeted sterically stabilized liposomes (SL). Spontaneous lung metastasis and angiogenesis assays show that YIGSR peptide anchored liposomes are significantly (P ≤ 0.01) effective in the prevention of lung metastasis and angiogenesis compared to free 5-fluorouracil (5-FU) and SL. YIGSR-SL was very effective in regression of tumors in BALB/c mice bearing B16F10 melanoma cells. Results indicate that YIGSR peptide anchored sterically stabilized liposomes bearing 5-FU are significantly (P ≤ 0.01) active against primary tumor and metastasis than the SL and free drug. Thus, YIGSR peptide anchored sterically stabilized liposomes hold potential of targeted cancer chemotherapeutics.

CNS vasculitis and stroke in neonatal lupus erythematosus: A case report and review of literature

Neonatal lupus erythematosus refers to the clinical spectrum of cardiac, cutaneous and other systemic abnormalities in neonates born to mothers with autoantibodies against Ro/SSA and La/SSB antigens. Isolated central nervous system involvement is very rare and has been described as transient vasculopathy only. We describe a 2-months-old girl who presented with acute ischemic stroke secondary to central nervous system vasculitis without any cardiac, cutaneous or hematological manifestations. The mother was pauci-symptomatic with raised anti-Ro autoantibody titers; the baby was positive for autoantibodies against Ro-antigen. Angiography confirmed vasculitis in cerebral vasculature. Our case highlights that neonatal lupus erythematosus can present with isolated nervous system manifestations and the vascular damage can be permanent in the form of vasculitis. Early recognition will help pediatricians identify such possible permanent complications in newborns with neonatal lupus erythematosus. A review of previously reported central nervous system manifestations of neonatal lupus is also presented.

Polymeric nanospheres modified with YIGSR peptide for tumor targeting

YIGSR peptide anchored pegylated nanospheres (YIGSR-SN) loaded with 5-fluorouracil (5-FU) were investigated for selective and preferential presentation of carrier contents at angiogenic endothelial cells over-expressing laminin receptors on and around tumor tissue and thus for assessing their targetability. Pegylated nanosphere (SN) without peptide conjugate were used for comparison. The average size of all nanosphere preparations prepared was ∼108 nm and maximum drug entrapment was 68.5 ± 5.2%. In vitro endothelial cell binding of nanospheres exhibited 8-fold higher binding of YIGSR-SN to HUVEC in comparison to the SN. Spontaneous lung metastasis and angiogenesis assays show that YIGSR peptide anchored nanospheres are significantly (p ≤ 0.05) effective in the prevention of lung metastasis and angiogenesis compared to free 5-FU and SN. In therapeutic experiments, 5-FU, SN, and YIGSR-SN were administered intravenously on day 4 at the dose of 10 mg 5-FU/kg body weight to B16F10 tumor bearing BALB/c mice resulting in effective regression of tumors in YIGSR-SN compared with free 5-FU and SN. Results indicate that YIGSR peptide anchored pegylated nanospheres bearing 5-FU are significantly (p ≤ 0.05) active against primary tumor and metastasis than the non-targeted pegylated nanospheres and free drug. Thus, YIGSR peptide anchored pegylated nanospheres hold potential of targeted cancer chemotherapeutics.

Pheochromocytoma of urinary bladder.

Pheochromocytoma of urinary bladder are rare tumors. They present with nonspecific clinical signs and symptoms, so imaging plays an important role in diagnosing and localizing the tumor. We present two cases of bladder pheochromocytoma, one of them presented with vague abdominal pain and the other with hematuria. Biphasic CT in both the cases showed hypervascular intravesical mass suggestive of bladder pheochromocytoma. The lesions were confirmed biochemically or on postoperative histopathology. A brief review of the imaging in bladder pheochromocytoma is also presented.