Nanosuspension: An Emerging Trend for Bioavailability Enhancement of Etodolac

Etodolac (ET) (poorly soluble drug) nanosuspensions were prepared by both pH shift method and antisolvent techniques in order to increase its dissolution rate. Various stabilizers were used, namely, Tween 20 and 80, HPMC, PVP K44, PVA, PEG 400, NaCMC, and β-cyclodextrin. The prepared nanosuspensions were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) and evaluated for their particle size, particle size distribution, and in vitro dissolution rate. In general, it was found that the antisolvent method for the preparation of ET nanosuspensions reduced the drug particle size to a higher extent compared to the pH shift method. The dissolution rate of ET in distilled water was markedly enhanced in the nanosized system, as more than 65% of drug dissolved in 10 min from all the nanosuspension formulations except F5 (stabilized with PVP K44) and F8 (stabilized with Tween 20), as compared to less than 20% of crude drug. Nanoparticles prepared by antisolvent method using Tween 80 as a stabilizer were selected for further in vivo study. The in vivo test demonstrated that nanoparticles of ET were well absorbed with a percentage drug absorption value 2.7 times more than that of micrometric size of crude ET

Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity and In Vivo Evaluation

In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates

A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies

Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested

Formulation of Indomethacin Colon Targeted Delivery Systems Using Polysaccharides as Carriers by Applying Liquisolid Technique

The present study aimed at the formulation of matrix tablets for colon-specific drug delivery (CSDD) system of indomethacin (IDM) by applying liquisolid (LS) technique. A CSDD system based on time-dependent polymethacrylates and enzyme degradable polysaccharides was established. Eudragit RL 100 (E-RL 100) was employed as time-dependent polymer, whereas bacterial degradable polysaccharides were presented as LS systems loaded with the drug. Indomethacin-loaded LS systems were prepared using different polysaccharides, namely, guar gum (GG), pectin (PEC), and chitosan (CH), as carriers separately or in mixtures of different ratios of 1 : 3, 1 : 1, and 3 : 1. Liquisolid systems that displayed promising results concerning drug release rate in both pH 1.2 and pH 6.8 were compressed into tablets after the addition of the calculated amount of E-RL 100 and lubrication with magnesium stearate and talc in the ratio of 1 : 9. It was found that E-RL 100 improved the flowability and compressibility of all LS formulations. The release data revealed that all formulations succeeded to sustain drug release over a period of 24 hours. Stability study indicated that PEC-based LS system as well as its matrix tablets was stable over the period of storage (one year) and could provide a minimum shelf life of two years

Combining hydrophilic chemotherapy and hydrophobic phytotherapy via tumor-targeted albumin–QDs nano-hybrids: covalent coupling and phospholipid complexation approaches

Abstract Background The rationale of this study is to combine the merits of both albumin nanoparticles and quantum dots (QDs) in improved drug tumor accumulation and strong fluorescence imaging capability into one carrier. However, premature drug release from protein nanoparticles and high toxicity of QDs due to heavy metal leakage are among challenging hurdles. Following this platform, we developed cancer nano-theranostics by coupling biocompatible albumin backbone to CdTe QDs and mannose moieties to enhance tumor targeting and reduce QDs toxicity. The chemotherapeutic water soluble drug pemetrexed (PMT) was conjugated via tumor-cleavable bond to the albumin backbone for tumor site-specific release. In combination, the herbal hydrophobic drug resveratrol (RSV) was preformulated as phospholipid complex which enabled its physical encapsulation into albumin nanoparticles. Results Albumin–QDs theranostics showed enhanced cytotoxicity and internalization into breast cancer cells that could be traced by virtue of their high fluorescence quantum yield and excellent imaging capacity. In vivo, the nanocarriers demonstrated superior anti-tumor effects including reduced tumor volume, increased apoptosis, and inhibited angiogenesis in addition to non-immunogenic response. Moreover, in vivo bioimaging test demonstrated excellent tumor-specific accumulation of targeted nanocarriers via QDs-mediated fluorescence. Conclusion Mannose-grafted strategy and QD-fluorescence capability were beneficial to deliver albumin nanocarriers to tumor tissues and then to release the anticancer drugs for killing cancer cells as well as enabling tumor imaging facility. Overall, we believe albumin–QDs nanoplatform could be a potential nano-theranostic for bioimaging and targeted breast cancer therapy

Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment

While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT–ALG/LF–RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression