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Polymers have a major role in the controlled delivery of pharmaceutical compounds to a targeted portion of the body. In this quest, a high priority research area is the targeted delivery of ophthalmic drugs to the interior regions of the eyes. Due to their complex anatomical/biochemical nature. This necessitates an advanced drug delivery cargo that could administer a therapeutic agent to the targeted location by evading various obstacles. The ongoing focus is to design an ophthalmic formulation by coupling it with a smart in situ forming polymeric hydrogel. These smart macromolecules have an array of unique theranostic properties and can utilize the in vivo biological parameters as a stimulus to change their macromolecular state from liquid to gel. The fast gelling hydrogel improves the corneal contact time, facilitates sustained drug release, resists the burst-out effect, and assists drug permeability to anterior regions. This review summarizes the rationale, scientific objectives, properties, and classification of the biologically important in situ hydrogels in the niche of ophthalmic drug delivery. The current trends and prospectives of the array of stimulus-responsive polymers, copolymers, and nanomaterials are discussed broadly. The crucial biointerfacial attributes with pros and cons are reviewed by investigating the effect of the nature of polymers as well as the ratio/percentage of additives and copolymers that influence the overall performance.

There has been extensive utilization of poloxamer 407 (PM) for the delivery of various ophthalmic drugs aimed at efficient ophthalmic drug delivery approach for longer precorneal residence time along with acceptable bioavailability of drugs. We have studied the effect of nanocellulose grafted collagen (CGC) on the performance of in situ gels based on PM for the controlled in vitro release of Ketorolac Tromethamine (KT). CGC has shown great influence evident by the reduction in PM critical gelation concentration, increased gel strength, and prolonged the release of loaded drugs compared with the virgin PM gel. The engineered nanocomposite formulations established an anomalous diffusion mechanism along with a Fickian diffusion controlled drug release for 1.5 & 1.75 w/v% CGC reinforced PM. Hence, the synthesized in situ nanocomposites are potential candidates for ophthalmic drug delivery system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Evaluation of the potential for oral sustained drug delivery of formulations with in-situ gelling properties is the main objective of the present investigation. Oral administration of aqueous dispersion of sodium alginate (1.5% w/v) containing calcium ions in complex form resulted in the formation of gel matrix as a consequence of the release of the calcium ions in the acidic environment of stomach fluid. Addition of methylcellulose, sodium chloride and polyethylene glycol improved the drug retention efficacy of the gel. In this investigation, the study on the influence of added excipients on the rheological and drug release properties of the formulations has been focused. In-vitro studies demonstrated diffusion-controlled release of paracetamol from the gels. The bioavailability of orally administered paracetamol from the in-situ gel F4 (composed of 1.5% sodium alginate, 1.5% methyl cellulose, 3% CaCO 3 , 2% NaCl 0.05% polyethylene glycol) administered in the stomach of rabbit, was more sustained as compared to the commercially available suspension Calpol® containing an identical dose of paracetamol., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This paper reports interesting differences between physical and mechanical properties of various membranes prepared from high and low molecular weight poly (vinyl alcohol) (PVA) and xanthan gum (XG) blends irradiated under low dose electron beam. The membranes were designed for sustained delivery of diltiazem hydrochloride through skin. Electron beam irradiation produced crosslinks and turned PVA into crystalline phase from its amorphous organization in the unirradiated state. PVA crystals were fibrillar at low XG content (1 wt.%) when the molecular weight was high while similar orientation at higher XG content (5 wt.%) when the molecular weight was low. Low molecular weight PVA-XG membranes showed equivalent physical properties under dry condition but wet-mechanical properties were superior for high molecular weight PVA-XG hybrids. Both of them showed slow and sustained diltiazem release but the later induced slightly slower release despite low drug encapsulation efficiency due to its better wet mechanical strength., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of thermo-reversible in situ gel. The purpose of this study was to examine the influence of different salts on the gelation, rheology and drug release of in situ gel based on methylcellulose. The gel temperature of 1% w/v methylcellulose (MC) was 60?C. It was found that 5?7% w/v sodium chloride (NaCl), 8?9% w/v potassium chloride (KCl), or 5% w/v sodium bicarbonate (NaHCO(3)) was capable of decreasing the gel temperature below physiological temperature, i.e. 37?C. Rheological studies indicated a large increase in viscosity at 37?C with the addition of salts in MC solutions. The duration of drug release from MC solution was 1.5?h. The significant observation was that the duration of drug release increased from 1.5?h to 3?5?h from salted MC solutions depending on the concentration and the type of salt. So, it can be concluded that the salted MC solutions were a better alternative than the MC solution to enhance the ocular bioavailability of the drug.

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent. [ABSTRACT FROM AUTHOR]

Increased incidence of antibiotic-resistant species calls for development of new types of nano-medicine that can be used for healing of bacteria-caused wounds, such as diabetic foot ulcer. As diabetic patients have inefficient defense mechanism against reactive oxygen species (ROS) produced in our body as a by-product of oxygen reduction, the process of wound healing takes longer epithelialisation period. Ceria nanoparticles (CNPs) are well-known for their antibacterial and ROS-scavenging nature. Yet till now no significant effort has been made to conjugate ceria nanoparticles with drugs to treat diabetic wounds. In this experiment, CNPs were synthesized in-house and clindamycin hydrochloride was loaded onto it by physical adsorption method for reactive oxygen species responsive drug delivery. Various physico-chemical characterisations such as Transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Energy dispersive X-ray, Thermogravimetric study etc. were performed to affirm the formation of both nanoceria along with drug encapsulated nanoceria. Both of these as-prepared formulations inhibited the growth of Gram-positive as well as Gram-negative bacteria confirmed by Disk diffusion study; exhibiting their antibacterial effect. In-vitro drug release study was carried out in physiological environment both in absence and presence of hydrogen peroxide solution to test the reactive ROS-responsiveness of the drug loaded nanocomposites. It also exhibited faster wound healing in diabetes-induced rats. Therefore, it could successfully lower the amount of serum glucose level, inflammation cytokines, hepatotoxic and oxidative stress markers in diabetic rats as confirmed by various ex vivo tests conducted. Thus, drug loaded ceria nanoparticles have the potential to heal diabetic wounds successfully and can be considered to be useful for the fabrication of appropriate medicated suppositories beneficial for diabetic foot ulcer treatment in future. [Display omitted] • Clindamycin hydrochloride was loaded onto nanoceria (CLIN@CNP) for diabetic wound healing study. • Successful drug loading onto nanoparticles with maximum loading of ≈ 22.5%, have been confirmed by TGA and UV spectral study. • Both neat drug and CLIN@CNP impede growth of Gram-positive besides Gram-negative bacteria signifying antibacterial activity. • In-vitro drug release data validated that CLIN@CNP exhibited ROS-responsive drug delivery for diabetic wound treatment. • Ex-vivo studies also confirmed establishment of nanoceria based futuristic model for diabetic treatment successfully. [ABSTRACT FROM AUTHOR]

ABSTRACT Hybrid membranes based on poly(vinyl alcohol) (PVA) of widely different molecular weights and ex situ nanosilica were synthesized and characterized as transdermal delivery device for Diltiazem hydrochloride. Investigations showed that change in PVA molecular weight strongly influenced physico-mechanicals of the hybrids especially at low nanosilica content than at higher levels. As for example at 1 wt %, low molecular weight PVA induced finer dispersion of silica nanoparticles resulting into higher dry state crystallinity and mechanical strength but slightly lower biocompatibility as compared to high molecular weight PVA. Those variations in physico-mechanicals finally affected Diltiazem retention and its elution from those membranes under physiological conditions. Low molecular weight PVA produced highest drug retention as well as slowest yet steady release than both high molecular weight PVA and neat PVA membranes. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2076-2086, 2013 [ABSTRACT FROM AUTHOR]

The article discusses a study about the development of an in-situ fast gelling vehicle for ophthalmic drug delivery. Using methylcellulose (MC), in combination with fructose and sodium citrate tribasic dihydrate (SC), Ketorolac Tromethamine (KT) was successfully formulated as an in-situ gelling system. The formulation is considered a viable alternative to conventional eye drops due to its ability to enhance precorneal residence time and consequently ocular bioavailability.

Non-toxic nanocomposites based bio-films obtained from methylcellulose (MC) can reduce environmental problems associated with synthetic polymers. A new facile route for the isolation of cellulose nano-crystals (CNC) from jute waste is successfully utilized here. The fabrication of CNC reinforced MC nanocomposites by film casting technique and the studies of the effect of CNC on the properties of the MC based nanocomposites have been reported. The synthesized nanocomposites have shown improved UV resistance, mechanical, barrier, and thermal properties. FTIR results established the physicochemical compatibility between the drug, MC and CNC in nanocomposites. In vitro permeation studies performed by using Franz diffusion cell revealed diffusion mediated sustained drug release from the devices due to the presence of interaction between MC and CNC through H-bonding, electrostatic interaction between the hydrophilic polymer/CNC chains with the drug and the formation of tortuous path. The nanocomposites can be used for edible packaging and transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this investigation was to develop a novel in situ gelling formulation based on poloxamer-407 (PM) for the sustained release of an ophthalmic drug. In an attempt to reduce the concentration of PM without compromising the in situ gelling capability and also to increase the drug release time, xanthan gum (XG) and guar gum (GG) were added into PM to develop different formulations. At concentrations of 18% and above, the PM was able to undergo sol–gel transition below body temperature. It was found that XG and GG at a weight ratio of 3:7 were able to convert PM solution into gel below body temperature at PM concentrations below 18%. Both the in vitro and in vivo studies indicated that the PM with an XG–GG combination had a better ability to retain the drug than PM itself. The results indicated that the developed in situ gelling formulations containing PM with XG–GG may be a better alternative than a conventional eye drop. [Copyright &y& Elsevier]

Abstract: Gelation temperature of MC was reduced from 59°C to 54°C with the addition of 10% PEG. Sodium tartrate (NaT) and sodium citrate (NaC) were added to the MC–PEG solution to further reduce the gelation temperature close to physiological temperature. Different techniques were used to measure the gelation temperature of all formulations. It was observed that NaC was more effective in reducing the gelation temperature of MC–PEG combination than NaT. Environmental scanning electron microscopy (ESEM) images of hydrogels containing NaC and NaT showed that NaC containing hydrogel having an interconnected microporous structure instead of the hollow rod like structure as in the case of NaT containing hydrogel. In vitro drug release studies showed that drug release time increased from 6 to 9h by only changing the type of salt from NaT to NaC in MC–PEG combination. [Copyright &y& Elsevier]

Abstract: The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol–gel transition at 61.2°C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV–vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC–PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9×103 to 1.3×105 and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×105) compared to PVA (9×103). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out. [Copyright &y& Elsevier]