Sai Prachetan Balguri - Academia.edu (original) (raw)
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Papers by Sai Prachetan Balguri
Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. ... more Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2 K to 20 K) grafted onto the phospho-lipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG–2K. Drug load in the formulations was maintained at 0.3%w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2 K–10 K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization stabilization characteristics into the formulations.
Purpose: The goal of the present study is to develop polymeric matrix films loaded with a combina... more Purpose: The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFSfree) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively.
Methods: Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFSfree, or a combination of DFSfree + DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol.
Results: Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFSfree + DFS:IR(1:1)(1 + 1) was twice that of only DFS:IR(1:1) film. In vivo, DFS solution and DFS:IR(1:1) suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFSfree and DFSfree + DFS:IR(1:1)(3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFSfree formulation.
Conclusion: DFSfree + DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.
Keywords: Ion exchange resins, immediate release formulations, ocular drug delivery, diclofenac sodium and polymeric matrix films
Purpose: The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid... more Purpose: The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery.
Methods: IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and
in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt.< 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the
SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies.
Results: For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 ± 5, 265 ± 8, and 227 ± 11 nm, respectively; the zeta potential was 22 ± 0.8, 27 ± 1.2, and 12.2 ± 2.3 mV, respectively; the polydispersity
index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 ± 0.9, 91.5 ± 3.2 and 99.8 ± 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular
penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo.
Conclusion: The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery
to anterior and posterior segment ocular tissues.
Purpose: The goal of the present study was to develop a poly (ethylene oxide) N10 (PEO N10) based... more Purpose: The goal of the present study was to develop a poly (ethylene oxide) N10 (PEO N10) based melt-cast matrix system for efficient and prolonged delivery of hesperetin (HT), a promising bioflavonoid, to the posterior segment of the eye through the topical route.
Methods: HT film was prepared by melt-cast method using PEO N10 and cut into 4 mm 2mm segments, each weighing 8 mg. This film was evaluated with respect to in vitro release rates and also transmembrane delivery across Spectra/Por membrane (MWCO: 10,000 Daltons) and isolated rabbit corneas. Ocular tissue concentrations were also determined postapplication of the film in ex vivo and in vivo models.
Results: HT release from the film was determined to be about 95.3% within 2 h. In vitro transcorneal flux was observed to be 0.58 ± 0.05 lg/min/cm2 across the isolated rabbit cornea. High levels of HT were detected in the retina-choroid (RC) and vitreous humor (VH) in the ex vivo model following topical application of the film. Significant levels of HT were observed in both anterior and posterior segment ocular tissues 1 h post topical application of the 10 and 20%w/w HT films on the rabbit eye. Moreover, HT was detected in the VH and RC even after 6 h following topical application of the film in vivo.
Conclusion: The results from this study suggest that the melt-cast films can serve as a viable platform for sustained topical delivery of bioflavonoids, and other therapeutic agents, into the back-of-the eye tissues.
The objective of the present study is to investigate the confounding effects, if any, of betacycl... more The objective of the present study is to investigate the confounding effects, if any, of betacyclodextrins (βCDs) on corneal permeability coefficients obtained from in vitro transmembrane diffusion studies. Transcorneal permeability studies were carried out with 2-hydroxypropyl-beta-cyclodextrin (HPβCD) and randomly methylated-beta-cyclodextrin (RMβCD) at 5 and 2.5%w/v in isotonic phosphate-buffered solution (IPBS) (pH 7.4). Rabbit corneas received from Pel-Freez Biologicals® were used for these studies. Propranolol hydrochloride (PHCl) (1 mg/mL) was used as the paracellular permeability marker. A series of permeation studies were carried out with IPBS as the control, with
CDs on the donor side only, CDs on the receiver side only, and CDs on both the donor and receiver sides. At the end of 1 or 3 h, corneas were collected and fixed using a solution containing 2%v/v glutaraldehyde+2%w/v paraformaldehyde+IPBS and histological examinations were performed (Excalibur Pathology, Inc). The order of transcorneal permeability of PHCl was found to be CDs on the receiver side > control (no CDs) ≈ CDs on both the receiver and donor sides > CDs on the donor side. Histology studies revealed that the corneal epithelial and endothelial layers remained intact in the control sets.
Damage to the cornea was observed in the order of CDs on the receiver side > CDs on the donor side > CDs on both sides > control. The use of CDs in solutions for in vitro permeation experiments with rabbit corneas needs to be carefully considered to avoid confounding effects in the data obtained.
Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. ... more Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2 K to 20 K) grafted onto the phospho-lipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG–2K. Drug load in the formulations was maintained at 0.3%w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2 K–10 K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization stabilization characteristics into the formulations.
Purpose: The goal of the present study is to develop polymeric matrix films loaded with a combina... more Purpose: The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFSfree) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively.
Methods: Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFSfree, or a combination of DFSfree + DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol.
Results: Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFSfree + DFS:IR(1:1)(1 + 1) was twice that of only DFS:IR(1:1) film. In vivo, DFS solution and DFS:IR(1:1) suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFSfree and DFSfree + DFS:IR(1:1)(3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFSfree formulation.
Conclusion: DFSfree + DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.
Keywords: Ion exchange resins, immediate release formulations, ocular drug delivery, diclofenac sodium and polymeric matrix films
Purpose: The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid... more Purpose: The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery.
Methods: IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and
in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt.< 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the
SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies.
Results: For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 ± 5, 265 ± 8, and 227 ± 11 nm, respectively; the zeta potential was 22 ± 0.8, 27 ± 1.2, and 12.2 ± 2.3 mV, respectively; the polydispersity
index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 ± 0.9, 91.5 ± 3.2 and 99.8 ± 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular
penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo.
Conclusion: The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery
to anterior and posterior segment ocular tissues.
Purpose: The goal of the present study was to develop a poly (ethylene oxide) N10 (PEO N10) based... more Purpose: The goal of the present study was to develop a poly (ethylene oxide) N10 (PEO N10) based melt-cast matrix system for efficient and prolonged delivery of hesperetin (HT), a promising bioflavonoid, to the posterior segment of the eye through the topical route.
Methods: HT film was prepared by melt-cast method using PEO N10 and cut into 4 mm 2mm segments, each weighing 8 mg. This film was evaluated with respect to in vitro release rates and also transmembrane delivery across Spectra/Por membrane (MWCO: 10,000 Daltons) and isolated rabbit corneas. Ocular tissue concentrations were also determined postapplication of the film in ex vivo and in vivo models.
Results: HT release from the film was determined to be about 95.3% within 2 h. In vitro transcorneal flux was observed to be 0.58 ± 0.05 lg/min/cm2 across the isolated rabbit cornea. High levels of HT were detected in the retina-choroid (RC) and vitreous humor (VH) in the ex vivo model following topical application of the film. Significant levels of HT were observed in both anterior and posterior segment ocular tissues 1 h post topical application of the 10 and 20%w/w HT films on the rabbit eye. Moreover, HT was detected in the VH and RC even after 6 h following topical application of the film in vivo.
Conclusion: The results from this study suggest that the melt-cast films can serve as a viable platform for sustained topical delivery of bioflavonoids, and other therapeutic agents, into the back-of-the eye tissues.
The objective of the present study is to investigate the confounding effects, if any, of betacycl... more The objective of the present study is to investigate the confounding effects, if any, of betacyclodextrins (βCDs) on corneal permeability coefficients obtained from in vitro transmembrane diffusion studies. Transcorneal permeability studies were carried out with 2-hydroxypropyl-beta-cyclodextrin (HPβCD) and randomly methylated-beta-cyclodextrin (RMβCD) at 5 and 2.5%w/v in isotonic phosphate-buffered solution (IPBS) (pH 7.4). Rabbit corneas received from Pel-Freez Biologicals® were used for these studies. Propranolol hydrochloride (PHCl) (1 mg/mL) was used as the paracellular permeability marker. A series of permeation studies were carried out with IPBS as the control, with
CDs on the donor side only, CDs on the receiver side only, and CDs on both the donor and receiver sides. At the end of 1 or 3 h, corneas were collected and fixed using a solution containing 2%v/v glutaraldehyde+2%w/v paraformaldehyde+IPBS and histological examinations were performed (Excalibur Pathology, Inc). The order of transcorneal permeability of PHCl was found to be CDs on the receiver side > control (no CDs) ≈ CDs on both the receiver and donor sides > CDs on the donor side. Histology studies revealed that the corneal epithelial and endothelial layers remained intact in the control sets.
Damage to the cornea was observed in the order of CDs on the receiver side > CDs on the donor side > CDs on both sides > control. The use of CDs in solutions for in vitro permeation experiments with rabbit corneas needs to be carefully considered to avoid confounding effects in the data obtained.