Liposomal formulations were significantly explored over the last decade for the ophthalmic drug delivery applications. These formulations are mainly composed of phosphatidylcholine (PC) and other constituents such as cholesterol and lipid-conjugated hydrophilic polymers. Liposomes are biodegradable and biocompatible in nature. Current approaches for topical delivery of liposomes are focused on improving the corneal adhesion and permeation by incorporating various bioadhesive and penetration enhancing polymers. In the case of posterior segment disorders improvement in intravitreal half life and targeted drug delivery to the retina is achieved by liposomes. In this paper we have attempted to summarize the applications of liposomes in the field of ophthalmic drug delivery by citing numerous investigators over the last decade.

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis.

Purpose The objectives were (i) to test in vivo functional activity of MRP2 on rabbit corneal epithelium and (ii) to evaluate modulation of P-gp and MRP2 mediated efflux of erythromycin when co-administered with corticosteroids. Methods Cultured rabbit primary corneal epithelial cells (rPCECs) was employed as an in vitro model for rabbit cornea. Cellular accumulation and bi-directional transport studies were conducted across Madin-Darby Canine Kidney (MDCK) cells overexpressing MDR1 and MRP2 proteins to delineate transporter specific interaction of steroids. Ocular pharmacokinetic studies were conducted in rabbits following a single-dose infusion of erythromycin in the presence of specific inhibitors and steroids. Results Bi-directional transport of erythromycin across MDCK-MDR1 and MDCK-MRP2 cells showed significant difference between BL-AP and AP-BL permeability, suggesting that erythromycin is a substrate for P-gp and MRP2. Cellular accumulation of erythromycin in rPCEC was inhibited by steroids in a dose dependent manner. MK571, a specific MRP inhibitor, modulated the aqueous humor concentration of erythromycin in vivo. Even, steroids inhibited P-gp and MRP2 mediated efflux with maximum increase in ka, AUC0−∞, Cmax and Clast values of erythromycin, observed with 6α-methyl prednisolone. Conclusion MRP2 is functionally active along with P-gp in effluxing drug molecules out of corneal epithelium. Steroids were able to significantly inhibit both P-gp and MRP2 mediated efflux of erythromycin.

The purpose of this investigation was to design novel pentablock copolymers (polylatide-polycaprolactone-polyethylene glycol- polycaprolactone-polylatide) (PLA-PCL-PEG-PCL-PLA) to prepare nanoparticle formulations which provide continuous delivery of steroids over a longer duration with minimal burst effect. Another purpose was to evaluate the effect of poly (L-lactide) (PLLA) or poly (D, L-lactide) (PDLLA) incorporation on crystallinity of pentablock copolymers and in vitro release profile of triamcinolone acetonide (selected as model drug) from nanoparticles. PLA-PCL-PEG-PCL-PLA copolymers with different block ratio of PCL/PLA segment were synthesized. Release of triamcinolone acetonide from nanoparticles was significantly affected by crystallinity of the copolymers. Burst release of triamcinolone acetonide from nanoparticles was significantly minimized with incorporation of proper ratio of PDLLA in the existing triblock (PCL-PEG-PCL) copolymer. Moreover, pentablock copolymer based nanoparticles exhibited continuous release of triamcinolone acetonide. Pentablock copolymer based nanoparticles can be utilized to achieve continuous near zero-order delivery of corticosteroids from nanoparticles without any burst effect.

The objective of this work was to delineate the effect of hydrophilic and hydrophobic polymeric additives on sol–gel transition and release profile of timolol maleate (TM) from poly (ethylene glycol)–poly (ε-caprolactone)– poly (ethylene glycol) (PEG–PCL–PEG)-based thermosensitive hydrogel. Polycaprolactone (hydrophobic additive) and polyvinyl alcohol (PVA) (hydrophilic additive) reduced critical gel concentration of PEG–PCL–PEG triblock polymer. The effect of PCL on sol–gel transition was more pronounced than PVA. However, with PCL no statistically significant difference in release profile was observed. The effect of PVA on release profile was more pronounced, which reduced the cumulative percentage release of TM from 86.4±0.8% to 73.7±1.8% over 316 h. Moreover, cytotoxicity of the hydrogel was also investigated utilizing rabbit primary corneal epithelial culture cells. No significant cytotoxicity of hydrogel alone or in presence of additives was observed. So, polymeric additive strategy serves as a valuable tool for optimizing TM release kinetics from PEG–PCL–PEG hydrogel matrix.

The objective of this research article is to report the synthesis and evaluation of novel pentablock copolymers for controlled delivery of macromolecules in the treatment of posterior segment diseases. Novel biodegradable PB copolymers were synthesized by sequential ring-opening polymerization. Various ratios and molecular weights of each block (polyglycolic acid, polyethylene glycol, polylactic acid, and polycaprolactone) were selected for synthesis and to optimize release profile of FITC-BSA, IgG, and bevacizumab from nanoparticles (NPs) and thermosensitive gel. NPs were characterized for particle size, polydispersity, entrapment efficiency, and drug loading. In vitro release study of proteins from NPs alone and composite formulation (NPs suspended in thermosensitive gel) was performed. Composite formulations demonstrated no or negligible burst release with continuous near zero-order release in contrast to NPs alone. Hydrodynamic diameter of protein therapeutics and hydrophobicity of PB copolymer exhibited significant effect on entrapment efficiency and in vitro release profile. CD spectroscopy confirmed retention of structural conformation of released protein. Biological activity of released bevacizumab was confirmed by in vitro cell proliferation and cell migration assays. It can be concluded that novel PB polymers can serve a platform for sustained delivery of therapeutic proteins.

Gene therapy holds promise for the treatment of many inherited and acquired diseases of the eye. Successful ocular to targeted cells with minimal toxicity. A major gene therapy interventions depend on challenge is to overcome both intracellular and extracellular barriers associated with ocular gene delivery. Numerous viral and nonviral vectors were explored to improve transfection efficiency. Among nonviral delivery systems, polymeric vectors have gained significant attention in recent years owing to their nontoxic and non-immunogenic nature. Polyplexes or nanoparticles can be prepared by interaction of cationic polymers with DNA, which facilitate cellular uptake, endolysosomal escape and nuclear entry through active mechanisms. Chemical modification of these polymers allows for the generation of flexible delivery vectors with desirable properties. In this article several synthetic and natural polymeric systems utilized for ocular gene delivery are discussed.

Angiogenesis is an essential process for disease progression in many solid tumors. There are several major cascade events in the angiogenic process that can be targeted to inhibit new blood vessel formation in the tumor tissue. The purpose of this work is to evaluate the inhibitory effect of paclitaxel (PTX) and rapamycin (RAP) as individual and in dual drug-loaded poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles on the angiogenic cascade processes of proliferation, migration, and tube formation. PEG-b-PLA PTX and/or RAP micelles were formed and characterized for size and drug loading. Sizes of individual and dual drug micelles were below 40 nm. PEG-b-PLA micelles significantly enhanced the aqueous solubility of PTX 1.80 mg/mL and RAP 1.60 mg/mL. The PTX-RAP dual drug PEG-b-PLA micelles were able to load PTX and RAP at 1.60 mg/mL for both drugs. Cell proliferation, apoptosis, tubule formation, and migration studies were performed in human umbilical vein endothelial cells (HUVEC). PTX and RAP in DMSO inhibited HUVEC proliferation with IC50 values of 0.82 ± 0.02 and 13 829 ± 681 nM, respectively, while the combination of both drugs in DMSO produced synergistic inhibition. PTX and RAP individual micelles had IC50 values of 6.3 ± 1.1 and 14 051 ± 821 nM, respectively. PTX and dual drug micelles had a synergistic inhibition effect on HUVEC proliferation through the induction of apoptosis via caspase 3/7 activity. In vitro tube formation assay demonstrated significant inhibition of tube formation upon treatment with dual drug micelles as compared to individual PTX or RAP micelles. Migration studies in HUVEC have shown that individual PTX micelles inhibited cell migration at 1 nM, while RAP micelles did not show any inhibitory effect on cell migration. Interestingly, the presence of RAP in the dual drug micelles was able to initiate the inhibition of the migration of HUVEC at 0.1 nM concentration of PTX. These results indicate that PTX-RAP dual drug micelles have antiangiogenic effects in vitro mediated through three major events in the angiogenic process and have strong potential for further development as antiangiogenic chemotherapy.