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Dive into the research topics where Sriramakamal Jonnalagadda is active.

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Featured researches published by Sriramakamal Jonnalagadda.


Journal of Physical Chemistry B | 2011

Prediction of solubility parameters and miscibility of pharmaceutical compounds by molecular dynamics simulations.

Jasmine Gupta; Cletus Nunes; Shyam Vyas; Sriramakamal Jonnalagadda

The objectives of this study were (i) to develop a computational model based on molecular dynamics technique to predict the miscibility of indomethacin in carriers (polyethylene oxide, glucose, and sucrose) and (ii) to experimentally verify the in silico predictions by characterizing the drug-carrier mixtures using thermoanalytical techniques. Molecular dynamics (MD) simulations were performed using the COMPASS force field, and the cohesive energy density and the solubility parameters were determined for the model compounds. The magnitude of difference in the solubility parameters of drug and carrier is indicative of their miscibility. The MD simulations predicted indomethacin to be miscible with polyethylene oxide and to be borderline miscible with sucrose and immiscible with glucose. The solubility parameter values obtained using the MD simulations values were in reasonable agreement with those calculated using group contribution methods. Differential scanning calorimetry showed melting point depression of polyethylene oxide with increasing levels of indomethacin accompanied by peak broadening, confirming miscibility. In contrast, thermal analysis of blends of indomethacin with sucrose and glucose verified general immiscibility. The findings demonstrate that molecular modeling is a powerful technique for determining the solubility parameters and predicting miscibility of pharmaceutical compounds.


Aaps Pharmscitech | 2000

A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery

Sriramakamal Jonnalagadda; Dennis H. Robinson

The purpose of this study was to design and characterize a zero-order bioresorbable reservoir delivery system (BRDS) for diffusional or osmotically controlled delivery of model drugs including macromolecules. The BRDS was manufactured by casting hollow cylindrical poly (lactic acid) (PLA): polyethylene glycol (PEG) membranes (10×1.6 mm) on a stainless steel mold. Physical properties of the PLA:PEG membranes were characterized by solid-state thermal analysis. After filling with drug (5 fluorouracil [5FU] or fluorescein isothiocyanate [FITC]-dextranmannitol, 5:95 wt/wt mixture) and sealing with viscous PLA solution, cumulative in vitro dissolution studies were performed and drug release monitored by ultraviolet (UV) or florescence spectroscopy. Statistical analysis was performed using Minitab® (Version 12). Differential scanning calorimetry thermograms of PLA:PEG membranes dried at 25°C lacked the crystallization exotherms, dual endothermal melting peaks. and endothermal glass transition observed in PLA membranes dried at −25°C. In vitro release studies demonstrated zero-order release of 5FU for up to 6 weeks from BRDS manufactured with 50% wt/wt PEG (drying temperature, 25°C). The release of FITC dextrans of molecular weights 4400, 42 000, 148 000, and 464 000 followed zero-order kinetics that were independent of the dextran molecular weight. When monitored under different concentrations of urea in the dissolution medium, the release rate of FITC dextran 42 000 showed a linear correlation with the calculated osmotic gradient (Δπ). PEG inclusion at 25°C enables manufacture of uniform, cylindrical PLA membranes of controlled permeability. The absence of molecular weight effects and a linear dependence of FITC-dextran release rate on Δπ confirm that the BRDS can be modified to release model macromolecules by an osmotically controlled mechanism.


Journal of Biomaterials Science-polymer Edition | 2004

Effect of thickness and PEG addition on the hydrolytic degradation of PLLA

Sriramakamal Jonnalagadda; Dennis H. Robinson

We previously demonstrated that cylindrical, biodegradable reservoirs fabricated with polylactide-polyethylene glycol (PLLA : PEG) films maintain constant permeability and enable zeroorder drug delivery for up to 6 weeks in vitro. This research proposes that PEG not only enhances permeability but also extends of life of the device by allowing the escape of soluble degraded monomers thereby minimizing autocatalysis of PLLA. To test this hypothesis, cylindrical PLLA films with varying PEG concentrations (0–30%, w/w) and film-thickness (0.05–0.18 mm) were fabricated, and their degradation rate and thermal properties monitored for 23 weeks in vitro. The decrease in PLLA molecular weight for all films followed bi-exponential kinetics that fit the equation:yt = M(e–K1t + e– K2t ), as was determined by a Pearsons coefficient > 0.95 for all films. The constant M was empirically determined to be equal to have the initial molecular weight of the degrading polymer. The value of K 1 was 5–60 orders of magnitude greater than K 2 and was attributed to the autocatalytic degradation based on its dependence on PEG concentration, film thickness, and correlation with the enthalpy change associated with the glass transition (ΔC p). K 2 was attributed to simple hydrolytic cleavage of PLLA. The decrease in the value of K 1 with PEG concentration and thickness, and the correlation of K 1 with ΔC p, confirmed that the PLLA degradation can be controlled by incorporating PEG, as well as by modifying thickness.


Journal of Biomedical Materials Research Part B | 2015

Enhanced osteogenic potential of human mesenchymal stem cells on electrospun nanofibrous scaffolds prepared from eri‐tasar silk fibroin

Niladri Nath Panda; Amit Biswas; Krishna Pramanik; Sriramakamal Jonnalagadda

This study evaluated the mechanical properties and osteogenic potential of a silk fibroin scaffold prepared from a 70:30 blend of Eri (Philosamia ricini) and Tasar (Antheraea mylitta) silk, respectively (ET scaffolds). An electrospinning process was used to prepare uniformly blended, fibrous scaffolds of nanoscale dimensions, as confirmed by scanning and transmission electron microscopy (fiber diameter < 300 nm). Similarly prepared scaffolds derived from gelatin and Bombyx mori (BM) silk fibroin were used as controls. Mechanical testing and atomic force microscopy showed that the ET scaffolds had significantly higher tensile strength (1.83 ± 0.13 MPa) and surface roughness (0.44 μm) compared with BM (1.47 ± 0.10 MPa; 0.37 μm) and gelatin scaffolds (0.6 ± 0.07 MPa; 0.28 μm). All scaffolds were exposed to mesenchymal stem cells isolated to human chord blood (hMSCs) for up to 28 days in vitro. Alamar blue and alkaline phosphatase assay showed greater attachment and proliferation for both ET and BM scaffolds compared with gelatin. The ET scaffolds also promoted greater differentiation of the attached hMSCs as evidenced by higher expression of RunX2, osteocalcin, and CD29/CD44 expression. ET scaffolds also showed significantly higher mineralization, as evidenced by glycosaminoglycan assay, alizarin red staining, and elemental analysis of crystalline composites isolated from the scaffolds.


Drug Delivery | 2011

Novel poly-DL-lactide-polycaprolactone copolymer based flexible drug delivery system for sustained release of ciprofloxacin

Vrushali Waknis; Sriramakamal Jonnalagadda

This research evaluated 7525DLPCL for soft flexible drug delivery systems. The effect of ciprofloxacin hydrochloride (CIP) loading at three levels (10, 20, and 30%), on thermo-mechanical properties was studied. CIP release was monitored for 12 weeks. Addition of CIP to 7525DLPCL caused an increase in compressive modulus of 7525DLPCL. CIP release was found to be sigmoidal with two phenomena (apart from a minor burst) contributing to release–diffusion and later diffusion plus erosion. An increased burst was observed with greater CIP loading and the majority of CIP (> 70%) was released as an effect of diffusion plus erosion. Additional factors, like the effect of CIP particle size, had no significant effect on drug release. Change in the implant shape from a cylinder (5 mm diameter; 3 mm thickness) to disc (6 mm diameter, 0.5 mm thickness) also failed to show a significant impact on drug release. Erosion of 7525DLPCL is a major contributing factor towards this release and other factors like shape of implants and particle size of drug have little effect on CIP release. Such flexible drug delivery systems offer new avenues for long-term skeletal drug delivery of antibiotics for conditions like osteomyelitis or periodontitis.


Journal of Biomaterials Science-polymer Edition | 2007

Physical characterization of thin semi-porous poly(L-lactic acid)/poly(ethylene glycol) membranes for tissue engineering

V. Swaminathan; R. Tchao; Sriramakamal Jonnalagadda

This study examines physical properties of solvent-cast poly(L-lactic acid) (PLLA): poly(ethylene glycol) PEG membranes as a function of PEG molecular weight (MW) and incubation in vitro for 6 weeks. PEGs of MW 400, 1450 and 8000 were used. The morphological, thermal, mechanical and permeability properties of the membranes were studied prior to and after 3 and 6 weeks of incubation in phosphate-buffered saline (PBS) at 37°C. The membranes showed a thickness of about 35±5 μm and were found to be semi-porous, with a non-porous surface as well as a porous surface with pore-diameters of 0.5–5 μm. The surface pore size was found to be a function of PEG MW used. All membranes were mechanically strong, with elastic moduli and tensile strength of 150–440 MPa and 7–36 MPa, respectively, all through the 6-week incubation period. The lower-MW PEGs plasticized PLLA based on high initial percent elongation; however, the effect was lost after 3 weeks of incubation in PBS. All membranes except those fabricated with PEG 8000 were impermeable for up to 6 weeks of incubation in PBS. Permeability studies showed that only PLLA:PEG 8000 membranes were permeable to methylene blue after 3 weeks of degradation.


Protein Expression and Purification | 2013

On-column refolding of bone morphogenetic protein-2 using cation exchange resin

Anuja M. Rane; Sriramakamal Jonnalagadda; Zhiyu Li

Refolding is often the bottle-neck step in producing recombinant proteins from inclusion bodies of Escherichia coli, especially for dimer proteins. The refolding process is protein specific, engaging a lot of time and cost to optimize conditions so that the thermodynamics favor protein refolding over competitive aggregation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic agent having significant applications in bone regeneration therapy. In this study, we present a novel solid-phase refolding method for rapid and efficient refolding of recombinant BMP-2 dimer from E. coli. We employed a weak cation exchange resin as the adsorbing support, with decreasing gradient of denaturing agent and exposure to oxidizing conditions for adequate disulfide bond formation. Refolded BMP-2 was further purified using size exclusion chromatography and analyzed for its secondary structure and biological activity. The purified BMP-2 dimer showed dose-dependent induction of alkaline phosphatase (ALP) activity in MC3T3 pre-osteoblast cells, thus translating the success of our refolding method. This simple and rapid method can also be applied in refolding and purification of other BMP-2 like dimer proteins.


Journal of Biomaterials Science-polymer Edition | 2013

Development and evaluation of cross-linked collagen-hydroxyapatite scaffolds for tissue engineering

Niladri Nath Panda; Sriramakamal Jonnalagadda; Krishna Pramanik

This study examines the tissue engineering potential of type I collagen cross-linked in the presence of hydroxyapatite (HAp). Scaffolds were prepared by controlled freezing followed by lyophilization of composite mixtures of collagen and HAp in acetic acid, followed by cross-linking with 0.3% glutaraldehyde. Scaffolds of three ratios were prepared, corresponding to collagen/HAp ratios of 1:2, 1:4, and 1:6. The scaffolds were evaluated for their microstructure, chemical and physical properties, swelling behavior, mechanical strength, biodegradability hemocompatability, cytocompatibility, and histopathology following subcutaneous implantation in Sprague Dawley rats. The collagen/HAp matrices showed a smaller pore size of 10–40 μm compared to 50–100 μm for pure collagen scaffolds. Pure collagen showed a mechanical strength of 0.25 MPa, and the value almost doubled for cross-linked composites with collagen/HAp ratio 1:6. The improvement in mechanical strength corresponded to a decrease in swelling and enzymatic degradation (measured by resistance to collagenases). FTIR spectra results in conjunction with scanning electron micrographs showed that cross-linking in the presence of HAp did not significantly alter the structure of collagen. MTT assay and calcein AM staining revealed prominent and healthy growth of mesenchymal stem cells in both the pure collagen as well as collagen:HAp composites of ratio 1:2. In vivo implantation in Sprague Dawley rats showed an initial acute inflammatory response during days 3 and 7, followed by a chronic, macrophage-mediated inflammatory response on days 14 and 28. Overall, a cross-linked collagen/HAp composite scaffold of ratio 1:2 was identified as having potential for further development in tissue engineering.


European Journal of Pharmaceutics and Biopharmaceutics | 2011

The design of flexible ciprofloxacin-loaded PLGA implants using a reversed phase separation/coacervation method.

Peter In Pyo Park; Michael Makoid; Sriramakamal Jonnalagadda

The purpose of this research is to design and characterize flexible PLGA-based implants for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro. This research uses a reversed phase separation/coacervation method to fabricate flexible PLA and PLGA: excipient implants with dichloromethane/mineral oil as solvent/non-solvent. Physical characterization was performed using thermal and mechanical analyses. Drug loading and release studies were performed with ciprofloxacin HCl as the model drug. Release kinetics was modeled to elucidate possible mechanisms of drug release. Four polymer-excipient combinations with glass transition temperatures less than 20°C and representing a wide range of Youngs moduli were shown to entrap up to 8% of ciprofloxacin HCl that could be released at a controlled rate for 65 days in vitro. The release rate could consistently fit a ternary Gaussian pattern with an R(2)>0.99. It was postulated that these release patterns could be related to ciprofloxacin that was loosely or poorly bound (burst release), trapped within the polymer matrix, or encapsulated by the polymer. These studies show that flexible implants can be fabricated from PLGA-based polymers for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro.


Journal of Microencapsulation | 2005

The effect of coencapsulation of bovine insulin with cyclodextrins in ethylcellulose microcapsules

R. L. Graves; Michael Makoid; Sriramakamal Jonnalagadda

Polymeric microcapsules have been widely investigated for protein delivery. Common problems include: low stability, low encapsulation efficiency, lack of uniformity, and burst release. Cyclodextrins (CDs) are known to enhance stability and solubility of proteins in solution. This research examines the effect of α-, β-, and γ-CDs on: (1) stability, (2) encapsulation, and (3) release of insulin from ethylcellulose microcapsules. All CDs improved thermal stability of insulin by lowering the enthalpy of unfolding by 16–52%. α- and γ-CDs also increased the encapsulation efficiency of insulin and improved uniformity of the microcapsule formulations. Two mathematical models were proposed to account for insulin release and consisted of multiple zero order and first order input processes, and a single first order output process. All CDs decreased the initial burst release of insulin by up to 30%. This research demonstrates the potential for CDs to improve stability, uniformity, and encapsulation of proteins in microcapsule formulations.

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Dennis H. Robinson

University of Nebraska Medical Center

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Anuja M. Rane

University of the Sciences

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Atithi Patel

University of the Sciences

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