Microneedles (MNs) are micron-scaled needles measuring 100 to 1000 μm that were initially explore... more Microneedles (MNs) are micron-scaled needles measuring 100 to 1000 μm that were initially explored for delivery of therapeutic agents across the skin. Considering the success in transcutaneous drug delivery, the application of microneedles has been extended to different tissues and organs. The review captures the application of microneedles to the oral mucosa, the eye, vagina, gastric mucosa, nail, scalp, and vascular tissues for delivery of vaccines, biologics, drugs, and diagnostic agents. The technology has created easy access to the poorly accessible segments of eye to facilitate delivery of monoclonal antibodies and therapeutic agents in management of neovascular disease. Microporation has been reported to drastically improve the drug delivery through the poorly permeable nail plate. Curved microneedles and spatially designed microneedle cuffs have been found to be capable of delivering stem cells and therapeutic macromolecules directly to the cardiac tissue and the vascular smooth muscle cells, respectively. Besides being minimally invasive and patient compliant, the technology has the potential to offer viable solutions to deliver drugs through impermeable barriers owing to the ability to penetrate several biological barriers. The technology has been successful to overcome the delivery hurdles and enable direct delivery of drug to the target sites, thus maximizing the efficacy thereby reducing the required dose. This review is an attempt to capture the non-dermatological applications of microneedles being explored and provides an insight on the future trends in the field of microneedle technology. Graphical abstract Pictorial representation of different microneedle application.
Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis ... more Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.
Quality by Design (QbD) is a systematic, scientific, holistic and proactive approach that begins ... more Quality by Design (QbD) is a systematic, scientific, holistic and proactive approach that begins with pre-defined objectives and emphasis on product, process understanding and process control. It essentially necessitates designing and developing the product and the manufacturing process to achieve the predefined product quality objectives. QbD identifies characteristics that are vital to quality from the patient’s point of view and converts them into critical quality attributes (CQAs) that the product should possess. Further, it establishes the limits, the design space, for critical process parameters (CPPs) and critical material attributes (CMAs) that affect the CQAs within which the process will be unaffected and consistently manufacture the desired product. This knowledge is then used to implement a flexible and robust manufacturing process that can adapt and yield a stable product. Risk assessment tools and design of experiments (DoE) are its integral components. This article gi...
Ulceration of gastro-intestinal mucosa is caused by disruption of normal balance of corrosive eff... more Ulceration of gastro-intestinal mucosa is caused by disruption of normal balance of corrosive effect of gastric acid and the protective effect of mucus on gastric epithelial cells. The major cause of ulcer is increased gastric secretions, which may be further aggravated by factors including NSAIDs, impaired production of somatostatins, Helicobacter pylori infection, by stress and dietary habits. Up to 80-90% of ulcers has been associated with H. pylori infection in the stomach. The parietal cells in the stomach secrete hydrochloric acid regulated by the protein H+/K+-ATPase also called proton pump. Acid secretion is also regulated by hormones such as gastrin, chemicals like acetylcholine and histamine. Acid neutralization was recognized as an effective treatment, however with the understanding of pathogenesis of peptic ulcer, treatment has become more effective. One approach for treating ulcer is to block the proton pump by using proton pump inhibitors like omeprazole, lansoprazole. In another approach, blocking of regulatory molecules that stimulate acid secretion like acetylcholine, histamine and gastrin either with anticholinergics or H2 receptor antagonist such as ranitidine, famotidine is effective. H.pylori infection can be eradicated using amoxycillin, clarithromycin, metronidazole or tetracycline. Combination therapy helps in complete eradication of peptic ulcer; one of the combinations, approved by USFDA is omeprazole with clarithromycin. Gastro retentive dosage forms may prove beneficial as they exhibit a prolonged gastric residence time and act locally and systemically.
The Journal of pharmacy and pharmacology, Jan 23, 2015
Tamoxifen (TMX), a non-steroidal antiestrogen is a first-line drug in the treatment and preventio... more Tamoxifen (TMX), a non-steroidal antiestrogen is a first-line drug in the treatment and prevention of all stages of estrogen-receptor-positive breast cancer. However, oxidative liver damage and hepatocarcinoma are the major problems associated with its long-term clinical use. The aim of this study was to investigate the ameliorative effect of phospholipid against TMX-induced hepatotoxicity. Fifteen female Sprague-Dawley rats were divided into three groups with five rats in each group. Group I received only standard diet and distilled water for 28 days and served as normal. Group II received TMX per day p.o., for 28 days and served as control, and group III received TMX-phospholipid complex (TMX-PLC) per day p.o., for 28 days. Rats were examined for the effect of phospholipid on TMX-induced depletion of antioxidant enzymes, serum biochemical parameters and induction of lipid peroxidation. Treatment with TMX-PLC significantly ameliorates the TMX-induced hepatotoxicity by diminishing t...
Journal of Nanopharmaceutics and Drug Delivery, 2014
ABSTRACT The present study was undertaken to evaluate the potential effect of combinatorial thera... more ABSTRACT The present study was undertaken to evaluate the potential effect of combinatorial therapy of solid lipid nanoparticles of curcumin (CUR-SLN) and doxorubicin (DOX-SLN) in a mammary carcinoma (MC) rat model.CUR-SLN was optimized by a 3-factor, 3-level central composite design and its impact on pharmacokinetic profile of CUR was evaluated in Sprague-Dawley rats. The combinatorial therapeutic protocol consisted of intravenous administration of DOX and DOX-SLN (2.5 mg/body weight/week) for five weeks with oral administration of CUR and CUR-SLN (50 mg/kg body weight/day) for 28 days. We evaluated efficacy of treatment based on body weight, tumor volume and survival analysis in 7, 12-dimethyl benz[α]anthraceneDMBA-induced MCrats. We also compared the toxicity of combination of CUR-SLN and DOX-SLN by evaluating oxidative stress levels, cardiac and kidney function tests, hematological parameters, TNF-α expression and histopathological examinations.The optimized parameters of CUR-SLN include: 10% stearic acid, homogenization time of 30 min and 4 % Pluronic F68 to obtain optimum particle size (262.73±8.34 nm)and entrapment efficacy (63.15±2.15%).CUR-SLN exhibited significant enhancement (p<0.05) in BA in comparison to CUR. CUR-SLN exhibited higher peak plasma concentration, increased area under the curve (12.54±0.012 vs. 0.221±0.002 µg/ml*h).In addition, efficacy and toxicity profiles distinctly demonstrated health and safety potential of CUR-SLN withDOX-SLN in comparison to other treatment groups.Further; CUR-SLN exhibited a potential significant protective role in DOX-associated toxicity.The collective results of efficacy and toxicity profile demonstrate that combinatorial therapy of CUR-SLN with DOX-SLN,in MC model,is safe and effective culminating in increased life span.
The objective of the present investigation was formulation of raloxifene loaded solid lipid nanop... more The objective of the present investigation was formulation of raloxifene loaded solid lipid nanoparticles (R-SLN) for oral administration and evaluation of its anticancer potential in 7,12- dimethylbenzanthracene (DMBA)-induced breast cancer in Sprague-Dawley rats. Optimized R-SLN formulation prepared by modified micro-emulsion method resulted in R-SLN of 288.0±28.5 nm size and 95.56% entrapment efficiency. R-SLN exhibited in vitro prolonged release of raloxifene for 72 h in phosphate buffered saline. R-SLN was stable in simulated gastro-intestinal (GIT) fluids consisting of pH 1.2, pH 7.4, simulated gastric fluid and simulated intestinal fluid. A two-fold increase was observed in raloxifene oral bioavailability from R-SLN. R-SLN exhibited enhanced efficacy and chemopreventive activity over pure raloxifene as indicated by evaluation of tumor burden (P < 0.001) and tumor incidence (P < 0.001). The results indicate the potential of raloxifene solid lipid nanoparticles in optimizing chemoprevention of breast cancer by R-SLN.
Microneedles (MNs) are micron-scaled needles measuring 100 to 1000 μm that were initially explore... more Microneedles (MNs) are micron-scaled needles measuring 100 to 1000 μm that were initially explored for delivery of therapeutic agents across the skin. Considering the success in transcutaneous drug delivery, the application of microneedles has been extended to different tissues and organs. The review captures the application of microneedles to the oral mucosa, the eye, vagina, gastric mucosa, nail, scalp, and vascular tissues for delivery of vaccines, biologics, drugs, and diagnostic agents. The technology has created easy access to the poorly accessible segments of eye to facilitate delivery of monoclonal antibodies and therapeutic agents in management of neovascular disease. Microporation has been reported to drastically improve the drug delivery through the poorly permeable nail plate. Curved microneedles and spatially designed microneedle cuffs have been found to be capable of delivering stem cells and therapeutic macromolecules directly to the cardiac tissue and the vascular smooth muscle cells, respectively. Besides being minimally invasive and patient compliant, the technology has the potential to offer viable solutions to deliver drugs through impermeable barriers owing to the ability to penetrate several biological barriers. The technology has been successful to overcome the delivery hurdles and enable direct delivery of drug to the target sites, thus maximizing the efficacy thereby reducing the required dose. This review is an attempt to capture the non-dermatological applications of microneedles being explored and provides an insight on the future trends in the field of microneedle technology. Graphical abstract Pictorial representation of different microneedle application.
Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis ... more Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.
Quality by Design (QbD) is a systematic, scientific, holistic and proactive approach that begins ... more Quality by Design (QbD) is a systematic, scientific, holistic and proactive approach that begins with pre-defined objectives and emphasis on product, process understanding and process control. It essentially necessitates designing and developing the product and the manufacturing process to achieve the predefined product quality objectives. QbD identifies characteristics that are vital to quality from the patient’s point of view and converts them into critical quality attributes (CQAs) that the product should possess. Further, it establishes the limits, the design space, for critical process parameters (CPPs) and critical material attributes (CMAs) that affect the CQAs within which the process will be unaffected and consistently manufacture the desired product. This knowledge is then used to implement a flexible and robust manufacturing process that can adapt and yield a stable product. Risk assessment tools and design of experiments (DoE) are its integral components. This article gi...
Ulceration of gastro-intestinal mucosa is caused by disruption of normal balance of corrosive eff... more Ulceration of gastro-intestinal mucosa is caused by disruption of normal balance of corrosive effect of gastric acid and the protective effect of mucus on gastric epithelial cells. The major cause of ulcer is increased gastric secretions, which may be further aggravated by factors including NSAIDs, impaired production of somatostatins, Helicobacter pylori infection, by stress and dietary habits. Up to 80-90% of ulcers has been associated with H. pylori infection in the stomach. The parietal cells in the stomach secrete hydrochloric acid regulated by the protein H+/K+-ATPase also called proton pump. Acid secretion is also regulated by hormones such as gastrin, chemicals like acetylcholine and histamine. Acid neutralization was recognized as an effective treatment, however with the understanding of pathogenesis of peptic ulcer, treatment has become more effective. One approach for treating ulcer is to block the proton pump by using proton pump inhibitors like omeprazole, lansoprazole. In another approach, blocking of regulatory molecules that stimulate acid secretion like acetylcholine, histamine and gastrin either with anticholinergics or H2 receptor antagonist such as ranitidine, famotidine is effective. H.pylori infection can be eradicated using amoxycillin, clarithromycin, metronidazole or tetracycline. Combination therapy helps in complete eradication of peptic ulcer; one of the combinations, approved by USFDA is omeprazole with clarithromycin. Gastro retentive dosage forms may prove beneficial as they exhibit a prolonged gastric residence time and act locally and systemically.
The Journal of pharmacy and pharmacology, Jan 23, 2015
Tamoxifen (TMX), a non-steroidal antiestrogen is a first-line drug in the treatment and preventio... more Tamoxifen (TMX), a non-steroidal antiestrogen is a first-line drug in the treatment and prevention of all stages of estrogen-receptor-positive breast cancer. However, oxidative liver damage and hepatocarcinoma are the major problems associated with its long-term clinical use. The aim of this study was to investigate the ameliorative effect of phospholipid against TMX-induced hepatotoxicity. Fifteen female Sprague-Dawley rats were divided into three groups with five rats in each group. Group I received only standard diet and distilled water for 28 days and served as normal. Group II received TMX per day p.o., for 28 days and served as control, and group III received TMX-phospholipid complex (TMX-PLC) per day p.o., for 28 days. Rats were examined for the effect of phospholipid on TMX-induced depletion of antioxidant enzymes, serum biochemical parameters and induction of lipid peroxidation. Treatment with TMX-PLC significantly ameliorates the TMX-induced hepatotoxicity by diminishing t...
Journal of Nanopharmaceutics and Drug Delivery, 2014
ABSTRACT The present study was undertaken to evaluate the potential effect of combinatorial thera... more ABSTRACT The present study was undertaken to evaluate the potential effect of combinatorial therapy of solid lipid nanoparticles of curcumin (CUR-SLN) and doxorubicin (DOX-SLN) in a mammary carcinoma (MC) rat model.CUR-SLN was optimized by a 3-factor, 3-level central composite design and its impact on pharmacokinetic profile of CUR was evaluated in Sprague-Dawley rats. The combinatorial therapeutic protocol consisted of intravenous administration of DOX and DOX-SLN (2.5 mg/body weight/week) for five weeks with oral administration of CUR and CUR-SLN (50 mg/kg body weight/day) for 28 days. We evaluated efficacy of treatment based on body weight, tumor volume and survival analysis in 7, 12-dimethyl benz[α]anthraceneDMBA-induced MCrats. We also compared the toxicity of combination of CUR-SLN and DOX-SLN by evaluating oxidative stress levels, cardiac and kidney function tests, hematological parameters, TNF-α expression and histopathological examinations.The optimized parameters of CUR-SLN include: 10% stearic acid, homogenization time of 30 min and 4 % Pluronic F68 to obtain optimum particle size (262.73±8.34 nm)and entrapment efficacy (63.15±2.15%).CUR-SLN exhibited significant enhancement (p<0.05) in BA in comparison to CUR. CUR-SLN exhibited higher peak plasma concentration, increased area under the curve (12.54±0.012 vs. 0.221±0.002 µg/ml*h).In addition, efficacy and toxicity profiles distinctly demonstrated health and safety potential of CUR-SLN withDOX-SLN in comparison to other treatment groups.Further; CUR-SLN exhibited a potential significant protective role in DOX-associated toxicity.The collective results of efficacy and toxicity profile demonstrate that combinatorial therapy of CUR-SLN with DOX-SLN,in MC model,is safe and effective culminating in increased life span.
The objective of the present investigation was formulation of raloxifene loaded solid lipid nanop... more The objective of the present investigation was formulation of raloxifene loaded solid lipid nanoparticles (R-SLN) for oral administration and evaluation of its anticancer potential in 7,12- dimethylbenzanthracene (DMBA)-induced breast cancer in Sprague-Dawley rats. Optimized R-SLN formulation prepared by modified micro-emulsion method resulted in R-SLN of 288.0±28.5 nm size and 95.56% entrapment efficiency. R-SLN exhibited in vitro prolonged release of raloxifene for 72 h in phosphate buffered saline. R-SLN was stable in simulated gastro-intestinal (GIT) fluids consisting of pH 1.2, pH 7.4, simulated gastric fluid and simulated intestinal fluid. A two-fold increase was observed in raloxifene oral bioavailability from R-SLN. R-SLN exhibited enhanced efficacy and chemopreventive activity over pure raloxifene as indicated by evaluation of tumor burden (P < 0.001) and tumor incidence (P < 0.001). The results indicate the potential of raloxifene solid lipid nanoparticles in optimizing chemoprevention of breast cancer by R-SLN.
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