In the present study, Cyclosporine A (CsA) was successfully incorporated into cationic solid lipid nanoparticles (SLN) for ocular application. Physicochemical characterizations of SLNs were analysed in detail during the storage period of 6 months. Due to the better characteristics like smaller particle size (248.00 ± 0.33 nm) with narrow size distribution (PI = 0.25 ± 0.00), high zeta potential (50.30 ± 0.78 mV) and more stable lipid structure, Dynasan® 116 structured FD4 (0.1% CsA) formulation was chosen for in vivo studies. Sheep were used in in vivo studies and 200 µL of formulation was applied to sheep’ eyes (n = 6) under veterinarian supervision. Samples were collected at pre-determined time intervals and were analysed by enzyme immune assay (EIA). CsA could be detected in both aqueous and vitreous humour samples for 48 h showing the ocular penetration of formulation. Release profiles were not decreased during 48 h indicating controlled and prolonged release of active agent from positively charged SLN formulations due to increased residence time in eyes. Similarities in CsA concentration data showed that inter-individual variance did not influence the ocular penetration of CsA when formulated as SLN.

Quercetin (Q) and rutin (R) are well known and most studied flavonoids due to their activities in reduction of inflammation, oxidative damage, platelet aggregation and inhibition of cancer proliferation. Despite their remarkable potentials they have limited oral bioavailability due to the low water solubility. Therefore in this study inclusion complexes of Q and R with hydroxypropyl-β-cyclodextrin (HP-β-CD) were formulated to improve the aqueous solubility, antiproliferative efficacy and also antioxidant activity of the flavonoids. According to the analyses results, aqueous solubilities of Q and R were increased up to ∼630 fold and ∼55 fold, respectively. ZP values were ranged between -21.7±0.3 mV and -6.1±0.8 mV showing the anionic structure of the complexes. ¹H-NMR analyses revealed the complex formation considering the shifts of the protons of the APIs as well as HP-β-CD. The in vitro release analyses revealed that the cumulative release of Q was decreased from 22.9 % to 18.1 and 15.2 for T9 and T 24 formulations respectively while the cumulative release of R increased from 26.8 % up to 64.5 % and 75.8 % with T14 and T24 formulations respectively. According MTT analyses results, Q showed higher antiproliferative effect in MDA-MB-231 and A549 cell lines compared to NIH-3T3 cell lines while R showed remarkable effect only on MDA-MB-231 cell lines at the end of 48 h of incubation period. A synergistic effect was observed in the formulation of combined flavonoid (Q/R) inclusion complexes and an antiproliferative effect was ordered as MDA-MB-231 > A549 > NIH-3T3. The selected complexes T9 (Q), T14 (R) and T24 (Q/R) have shown the highest antioxidant activity with 93.8 %, 65.3 % and 93.1 % respectively with DPPH analyses. In conclusion incoporation of Q, R and Q/R to HP-β-CD based inclusion complexes have great potentials with enhanced in vitro dissolution characteristics and antiproliferative effects on different types of cancer cell lines for efficient treatment of severe disorders.

Introduction: A major problem in ocular therapeutics with classical formulations is the maintenance of an effective drug concentration at the site of action for a long period of time. Enhancement of ocular bioavailability with increased dose penetration and longer retention time at desired sites can be achieved by recent formulations. Chitosan stands out with its unique structural advantageous characteristics for different types of formulations like in situ gelling systems, micro- and nanoparticles, inserts, etc. Areas covered: In this review, the authors focus on ocular therapeutics and the characteristics that make chitosan more acceptable in ocular applications. Expert opinion: Chitosan seems to be one of the most promising polymeric carriers for both hydrophilic and lipophilic drugs for ocular application.

Despite being the most effective hypolipidemic agent, poor physicochemical properties of Rosuvastatin calcium (RCa) remain challenging obstacles in development of pharmaceutical dosage forms. Inclusion complexes (ICs) of RCa with cyclodextrin (CD) derivatives; methyl-beta-cyclodextrin (M-β-CD) and sulfobutylether-beta-cyclodextrin (SBE-β-CD; Captisol^®) were formulated by kneading and freeze-drying (lyophilization) methods. Pysicochemical properties of ICs were evaluated by SEM, DSC, XRD, FT-IR, ¹H-NMR analyses. Entrapment efficiency (EE), water solubility, in vitro release analyses were also performed. Safety and efficacy of the ICs were analyzed by cytotoxicity and permeation studies on Caco-2 cell lines. Both CDs indicated A_L type phase solubility diagrams showing that [1:1] molar ratio. Apparent stability constants (K_1:1) were found to be 60.93 M⁻¹ for M-β-CD and 158.07 M⁻¹ for Captisol^®. High EE in the range of 93.50% to 105.40% were achieved. Molar solubility of RCa was increased 3.7 and 4.1 fold with M-β-CD and Captisol^® ICs respectively. In vitro release analyses have indicated the equivalence of dissolution profiles for M-β-CD and Captisol^® based ICs to that of pure RCa (f₂ > 50). Cytotoxicity studies on Caco-2 cell lines have revealed the safety of ICs for oral use. Permeability studies demonstrated that selected lyophilized F6 formulation have shown the best permeation rate with P_app value of 3.08x10⁻⁷ cm.sec⁻¹. Considering greater water solubility, lower toxicity, high efficiency of complexation as well as, RCa-like permeability and in vitro release behavior at pH 6.8; Captisol^® based lyophilized F6 formulation was selected as the best IC to be used in oral dosage forms of RCa.