Mohd Cairul Iqbal Mohd Amin

A review of bacterial cellulose-based drug delivery systems: their biochemistry, current approaches and future prospects.

The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material.

PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery

UNLABELLED Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers. STATEMENT OF SIGNIFICANCE It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw readers attention, specifically, towards PEGylated PAMAM dendrimers.

Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model.

Natural polymer-based hydrogels are of interest to health care professionals as wound dressings owing to their ability to absorb exudates and provide hydration for healing. The aims of this study were to develop and characterize bacterial cellulose/acrylic acid (BC/AA) hydrogels synthesized by electron beam irradiation and investigate its wound healing potential in an animal model. The BC/AA hydrogels were characterized by SEM, tensile strength, water absorptivity, and water vapor transmission rate (WVTR). The cytotoxicity of the hydrogels was investigated in L929 cells. Skin irritation and wound healing properties were evaluated in Sprague-Dawley rats. BC/AA hydrogels had a macroporous network structure, high swelling ratio (4000-6000% at 24h), and high WVTR (2175-2280 g/m(2)/day). The hydrogels were non-toxic in the cell viability assay. In vivo experiments indicated that hydrogels promoted faster wound-healing, enhanced epithelialization, and accelerated fibroblast proliferation compared to that in the control group. These results suggest that BC/AA hydrogels are promising materials for burn dressings.

Purification, characterization and comparative studies of spray-dried bacterial cellulose microparticles.

Bacterial cellulose (BC) is a biopolymer with significant potential for the development of novel materials. This work aimed to prepare and characterize BC powders from nata de coco, and assess the possible enhancement of the powder properties by spray drying. Therefore, BC powders prepared by acid treatment and mechanical processing were spray-dried, and characterized according to their morphology, flowability, thermal stability, water retention capacity, and compared with commercial microcrystalline cellulose (MCC). The powders redispersibility and suspensions rheology were also evaluated. SEM showed that spray-dried BC microparticles exhibited semispherical shape and had flow rate of 4.23 g s(-1) compared with 0.52 g s(-1) for MCC. Particle size analysis demonstrated that spray-dried BC microparticles could be redispersed. TGA showed that BC samples had higher thermal stability than MCC. Water retention capacities of BC samples were greater than MCC. These findings provide new insight on the potential applications of spray-dried BC as a promising pharmaceutical excipient.

Rapid Synthesis of Superabsorbent Smart-Swelling Bacterial Cellulose/Acrylamide-Based Hydrogels for Drug Delivery

This study evaluated the effect of solubilized and dispersed bacterial cellulose (BC) on the physicochemical characteristics and drug release profile of hydrogels synthesized using biopolymers. Superabsorbent hydrogels were synthesized by graft polymerization of acrylamide on BC solubilized in an NaOH/urea solvent system and on dispersed BC by using N,N′-methylenebisacrylamide as a crosslinker under microwave irradiation. Fourier transform infrared spectroscopy analysis of the resulting hydrogels confirmed the grafting, and an X-ray diffraction pattern showed a decrease in the crystallinity of BC after the grafting process. The hydrogels exhibited pH and ionic responsive swelling behavior, with hydrogels prepared using solubilized BC (SH) having higher swelling ratios. Furthermore, compared to the hydrogels synthesized using dispersed BC, the hydrogels synthesized using solubilized BC showed higher porosity, drug loading efficiency, and release. These results suggest the superiority of the hydrogels prepared using solubilized BC and that they should be explored further for oral drug delivery.

Development and physicochemical characterization of alginate composite film loaded with simvastatin as a potential wound dressing

Previously, studies have demonstrated that topical application of simvastatin can promote wound healing in diabetic mice via augmentation of angiogenesis and lymphangiogenesis. This study aimed to formulate and characterize simvastatin in alginate-based composite film wound dressings. Biopolymers used for composite films were sodium alginate blended with pectin or gelatin. The films were prepared and characterized based on their physical properties, surface morphology, mechanical strength and rheology. Then, in vitro drug releases from the films were investigated and, finally, the cell viability assay was performed to assess the cytotoxicity profile. From the pre-formulation studies, alginate/pectin composite film showed to possess desirable wound dressing properties and superior mechanical properties. The in vitro drug release profile revealed that alginate/pectin film produced a controlled release drug profile, and cell viability assay showed that the film was non-toxic. In summary, alginate/pectin composite film is suitable to be formulated with simvastatin as a potential wound dressing.

Biocompatible and Mucoadhesive Bacterial Cellulose -g- Poly(acrylic acid) Hydrogels for Oral Protein Delivery

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid) hydrogels were investigated for their potential use as an oral delivery system for proteins. These hydrogels were synthesized using electron beam irradiation without any cross-linking agents, thereby eliminating any potential toxic effects associated with cross-linkers. Bovine serum albumin (BSA), a model protein drug, was loaded into the hydrogels, and the release profile in simulated gastrointestinal fluids was investigated. Cumulative release of less than 10% in simulated gastric fluid (SGF) demonstrated the potential of these hydrogels to protect BSA from the acidic environment of the stomach. Subsequent conformational stability analyses of released BSA by SDS-PAGE, circular dichroism, and an esterase activity assay indicated that the structural integrity and bioactivity of BSA was maintained and preserved by the hydrogels. Furthermore, an increase in BSA penetration across intestinal mucosa tissue was observed in an ex vivo penetration experiment. Our fabricated hydrogels exhibited excellent cytocompatibility and showed no sign of toxicity, indicating the safety of these hydrogels for in vivo applications.

Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model.

In this study, hydroxytyrosol (HT; a potent antioxidant) was co-administered with hydrocortisone (HC) to mitigate the systemic adverse effects of the latter and to provide additional anti-inflammatory and antioxidant benefits in the treatment of atopic dermatitis (AD). The co-loaded nanoparticles (NPs) prepared had shown different particle sizes, zeta potentials, loading efficiencies, and morphology, when the pH of the chitosan solution was increased from 3.0 to 7.0. Ex vivo permeation data showed that the co-loaded NPs formulation significantly reduced the corresponding flux (17.04μg/cm(2)/h) and permeation coefficient (3.4×10(-3)cm/h) of HC across full-thickness NC/Nga mouse skin. In addition, the NPs formulation showed higher epidermal (1560±31μg/g of skin) and dermal (880±28μg/g of skin) accumulation of HC than did a commercial HC formulation. Moreover, an in vivo study using an NC/Nga mouse model revealed that compared to the other treatment groups, the group treated with the NPs formulation efficiently controlled transepidermal water loss (13±2g/m(2)/h), intensity of erythema (207±12), and dermatitis index (mild). In conclusion, NPs co-loaded with HC/HT is proposed as a promising system for the percutaneous co-delivery of anti-inflammatory and antioxidative agents in the treatment of AD.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

Background Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. Methods FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.

Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels for oral controlled release drug delivery.

Abstract This study evaluated the potential of stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug delivery carriers. Hydrogels were synthesized by graft copolymerization of the monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation technique. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting. XRD showed that the crystallinity of BC was reduced by grafting, whereas an increase in the thermal stability profile was observed in TGA. SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading. The hydrogels demonstrated a pH-responsive swelling behavior, with decreased swelling in acidic media, which increased with increase in pH of the media, reaching maximum swelling at pH 7. The release profile of the hydrogels was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that hydrogels may be suitable drug carriers for oral controlled release of drug delivery in the lower gastrointestinal tract.