Browsing by Author "M.S. Muthu"

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Antibiofilm Potential of Silver Sulfadiazine-Loaded Nanoparticle Formulations: A Study on the Effect of DNase-I on Microbial Biofilm and Wound Healing Activity
(American Chemical Society, 2019) Krishna Kumar Patel; D. Bhavya Surekha; Muktanand Tripathi; Md. Meraj Anjum; M.S. Muthu; Ragini Tilak; Ashish Kumar Agrawal; Sanjay Singh
Biofilm resistance is one of the severe complications associated with chronic wound infections, which impose extreme microbial tolerance against antibiotic therapy. Interestingly, deoxyribonuclease-I (DNase-I) has been empirically proved to be efficacious in improving the antibiotic susceptibility against biofilm-associated infections. DNase-I hydrolyzes the extracellular DNA, a key component of the biofilm responsible for the cell adhesion and strength. Moreover, silver sulfadiazine, a frontline therapy in burn wound infections, exhibits delayed wound healing due to fibroblast toxicity. In this study, a chitosan gel loaded with solid lipid nanoparticles of silver sulfadiazine (SSD-SLNs) and supplemented with DNase-I has been developed to reduce the fibroblast cytotoxicity and overcome the biofilm-imposed resistance. The extensive optimization using the Box-Behnken design (BBD) resulted in the formation of SSD-SLNs with a smooth surface as confirmed by scanning electron microscopy and controlled release (83%) for up to 24 h. The compatibility between the SSD and other formulation excipients was confirmed by Fourier transform infrared, differential scanning calorimetry, and powder X-ray diffraction studies. Developed SSD-SLNs in combination with DNase-I inhibited around 96.8% of biofilm of Pseudomonas aeruginosa as compared to SSD with DNase-I (82.9%). In line with our hypothesis, SSD-SLNs were found to be less toxic (cell viability 90.3 ± 3.8% at 100 μg/mL) in comparison with SSD (Cell viability 76.9 ± 4.2%) against human dermal fibroblast cell line. Eventually, the results of the in vivo wound healing study showed complete wound healing after 21 days' treatment with SSD-SLNs along with DNase-I, whereas marketed formulations SSD and SSD-LSNs showed incomplete healing after 21 days. Data in hand suggest that the combination of SSD-SLNs with DNase-I is an effective treatment strategy against the biofilm-associated wound infections and accelerates wound healing. © 2019 American Chemical Society.
Development of repaglinide loaded solid lipid nanocarrier: Selection of fabrication method
(2010) M.K. Rawat; A. Jain; A. Mishra; M.S. Muthu; S. Singh
Repaglinide solid lipid nanoparticles (RG-SLN) were fabricated using stearic acid as lipid. Pluronic F68 (PLF68) and soya lecithin were used as a stabilizer. SLNs were prepared by modified solvent injection and ultrasonication methods. SLNs prepared with modified solvent injection method have larger particle size (360±2.5nm) than prepared with ultrasonication method (281±5.3nm). The zeta potential of the prepared formulations by these two methods varied from - 23.10 ±1.23 to -26.01 ±0.89 mV. The maximum entrapment efficiency (62.14 ±1.29%) was obtained in modified solvent injection method. The total drug content was nearly same (98%) in both the methods. In vitro release studies were performed in phosphate buffer (pH 6.8) with 0.5% sodium lauryl sulphate (SLS) using dialysis bag diffusion technique. The cumulative drug release was 30% and 50% within 2 hrs in modified solvent injection and ultrasonication method, respectively. This indicates that RG-SLN prepared from modified injection method released the drug more slowly than SLNs prepared with ultrasonication method. Differential scanning calorimetry indicates that repaglinide (RG) entrapped in the solid lipid nanoparticles (SLN) exist in an amorphous or molecular state. Repaglinide loaded solid lipid nanoparticles prepared with both methods were of spherical shape as observed by transmission electron microscopy (TEM). These results suggest that modified solvent injection method is more suitable for preparation of repaglinide SLNs using stearic acid. © 2010 Bentham Science Publishers Ltd.
Effect of embelin on lithium-induced nephrogenic diabetes insipidus in albino rats
(2012) Ashish K Sahu; M.K. Gautam; Pradeep T Deshmukh; Lokendra S Kushwah; Narendra Silawat; Zafar Akbar; M.S. Muthu
Objective: To evaluate the nephroprotective and anti-polyuric role of embelin on lithium induced nephrogenic diabetes insipidus (NDI) in albino rats. Methods: NDI induced by lithium chloride (4 meq/kg/day, i.p. for 6 days) which leads to huge amount of urine excretion. After induction of NDI, embelin (50 and 100mg/kg) was administered orally, once daily for 21 day in rats and N-acetyl cysteine (10mg/kg, twice daily, i.p.) was used as a standard drug for treatment of NDI. The body weight, urine protein, urine creatinine, plasma creatinine, blood urea nitrogen were assessed at 0, 7, 14 and 21 day. At the end of the study glutathione (GSH) content in kidney was assessed and histopathology of kidney was performed. Results: Embelin 50 and 100 mg/kg showed increase in the body weight and decrease in plasma and urine creatinine, blood urea nitrogen levels, and urine protein level. Embelin acts as a potent antioxidant; it increases the level of glutathione in kidney. Histopathological examination of the kidney indicated that embelin 50 and 100 mg/kg were reduced the vascular degeneration of tubules as well as slight degeneration and dilatation of renal tubules, however N-actyl cysteine (NAC) treated rats showed normal glomeruli and renal tubule with slight degeneration. Conclusions: Embelin seemed to be effective in NDI by its predominant effect on promoting antioxidant status and decrease the urine excretion may be due to the blocking of sodium channels. © 2012 Asian Pacific Tropical Medicine Press.
Enhanced transdermal delivery of ketoprofen from bioadhesive gels
(2009) S. Singh; B. Gajra; M. Rawat; M.S. Muthu
The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of bioadhesive gels of ketoprofen by using gelling polymers like sodium carboxymethylcellulose, xanthan gum, poloxamer 407 and carbopol 934P as bioadhesive polymer with and without penetration enhancer (oleic acid). The effect of oleic acid as a penetration enhancer was examined when it was added to the bioadhesive formulations. Gels were evaluated for bioadhesive force and viscosity. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cell using excised rat abdominal skin. Carrageenan induced rat paw edema model was used to investigate their in vivo performance. The commercial formulation of ketoprofen was used as a reference formulation. The in vitro permeation studies indicate that ketoprofen bioadhesive gel of poloxamer 407 with penetration enhancer was superior to gels of sodium carboxymethylcellulose and xanthan gum with penetration enhancer (oleic acid). The permeation rate of ketoprofen from poloxamer 407 based bioadhesive gel with 15% v/w penetration enhancer was higher (rat abdominal skin flux = 0.421 ± 0.032 mg/cm2/h) than the permeation rate of sodium carboxymethylcellulose and xanthan gum based bioadhesive gel with 15% v/w penetration enhancer. In the paw edema test poloxamer 407 based bioadhesive gel with 15% v/w penetration enhancer showed the best permeation and effectiveness. The in vitro and in vivo studies showed that bioadhesive gels of ketoprofen could be used for effective therapy.
Intra-arterial instillation of a nociceptive agent modulates cardiorespira-tory parameters involving 5-ht3 and trpv1 receptors in anesthetized rats
(Bentham Science Publishers, 2021) Sanjeev K. Singh; M.S. Muthu; Ravindran Revand; Maloy B. Mandal
Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instil-lation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 μM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykin-in-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 μg/kg), 5-HT3-antag-onist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventila-tory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1-antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats. © 2021 Bentham Science Publishers.
Nanoparticles based on PLGA and its co-polymer: An overview
(2009) M.S. Muthu
Poly (D, L-lactide-co-glycolide) (PLGA) is approved by the Food and Drug Administration for drug delivery use. The polymeric nanoparticles based on PLGA and its co-polymer are designed for controlled and targeted drug delivery. Also, PLGA and its co-polymer are important in designing nanoparticles with desired characteristics such as biocompatibility, biodegradation, particle size, surface properties, drug release and targetability. This review focuses on the polymer literature, methods for preparation of nanoparticles and recent studies on the nanoparticles based on PLGA and its co-polymer for the conventional and targeted delivery of drugs by various routes.
Poly (D, L-lactide) nanosuspensions of risperidone for parenteral delivery: Formulation and in-vitro evaluation
(2009) M.S. Muthu; S. Singh
Risperidone, an "atypical" antipsychotic drug, having large scope for prolonged psychotic treatments through novel parenteral drug delivery systems. Polymeric nanoparticles suspensions containing risperidone made of poly (D, L-Lactide) were designed by nanoprecipitation method using polymeric stabilizer (Pluronic® F-68 or Pluronic® F-127). The prepared nanosuspensions were characterized for particle size by photon correlation spectroscopy and scanning electron microscopy. The free dissolved drug in the nanosuspension was determined by bulk equilibrium reverse dialysis bag technique. In vitro release studies were carried out using dialysis bag diffusion technique. The particle size of the prepared nanoparticles in the nanosuspensions ranged between 78-184 nm. Nanoparticles of risperidone in the nanosuspensions were obtained with high encapsulation efficiency (91-94%). The drug release from the risperidone nanosuspension was sustained in some batches for more than 24 h with 75% drug release whereas release from risperidone solution showed release within 1.5 h. The release pattern of drug is analyzed and found to follow first order equation and Fickian diffusion kinetics. These studies suggest the feasibility of formulating risperidone loaded poly (D, L-Lactide) nanoparticles suspension for the treatment of psychotic disorders. © 2009 Bentham Science Publishers Ltd.
Preparation and evaluation of buccal bioadhesive films containing clotrimazole
(2008) S. Singh; S. Jain; M.S. Muthu; S. Tiwari; R. Tilak
Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms. The aim of present study was to prepare and evaluate buccal bioadhesive films of clotrimazole for oral candidiasis. The film was designed to release the drug at a concentration above the minimum inhibitory concentration for a prolonged period of time so as to reduce the frequency of administration of the available conventional dosage forms. The different proportions of sodium carboxymethylcellulose and carbopol 974P (CP 974P) were used for the preparation of films. Carbopol was used to incorporate the desired bioadhesiveness in the films. The films were prepared by solvent casting method and evaluated for bioadhesion, in vitro drug release and effectiveness against Candida albicans. In vitro drug release from the film was determined using a modified Franz diffusion cell while bioadhesiveness was evaluated with a modified two-arm balance using rabbit intestinal mucosa as a model tissue. Films containing 5% CP 974P of the total polymer were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The microbiological studies revealed that drug released from the film could inhibit the growth of C. albicans for 6 h. The drug release mechanism was found to follow non-Fickian diffusion. © American Association of Pharmaceutical Scientists 2008.
Preparation and evaluation of buccal bioadhesive tablets containing clotrimazole
(2008) S. Singh; S. Jain; M.S. Muthu; R. Tilak
Buccal bioadhesive tablets of clotrimazole (CTZ) and clotrimazole: hydroxypropyl-β-cyclodextrin (CTZ-HPβCD) complex were prepared by using polymer xanthan gum in combination with carbopol 974P. The prepared buccal bioadhesive tablet formulations were evaluated for physicochemical characteristics (weight, hardness, friability, diameter, and drug content), swelling index, microenvironment pH, in-vitro drug release, bioadhesion strength, residence time and duration of antifungal activity (in-vitro). The dissolution of CTZ from the prepared tablets into phosphate buffer (pH 6.8) was controlled up to 8 h. All the prepared tablets gave reasonable in-vitro residence time (7.13 - 9.34 h). X-ray diffraction (XRD) studies of the CTZ-HPβCD complex, made by kneading and freeze-dried method, showed no CTZ crystal signals, demonstrating the inclusion of CTZ in the hydrophobic cavity of hydroxypropyl-β-cyclodextrin (HPβCD) and formation of amorphous inclusion complex. Duration of the antifungal activity was measured by the inhibition zone of Candida albicans by agar diffusion assay. It is evident from the results obtained, the prepared buccal bioadhesive tablets of CTZ would markedly prolong the duration of the antifungal activity and may prove to be a viable alternative to the conventional local oral medication. © 2008 Bentham Science Publishers Ltd.