Traditional Drug Formulations Research Articles

Liposome-Hydrogel Composites for Controlled Drug Delivery Applications.

Various controlled delivery systems (CDSs) have been developed to overcome the shortcomings of traditional drug formulations (tablets, capsules, syrups, ointments, etc.). Among innovative CDSs, hydrogels and liposomes have shown great promise for clinical applications thanks to their cost-effectiveness, well-known chemistry and synthetic feasibility, biodegradability, biocompatibility and responsiveness to external stimuli. To date, several liposomal- and hydrogel-based products have been approved to treat cancer, as well as fungal and viral infections, hence the integration of liposomes into hydrogels has attracted increasing attention because of the benefit from both of them into a single platform, resulting in a multifunctional drug formulation, which is essential to develop efficient CDSs. This short review aims to present an updated report on the advancements of liposome-hydrogel systems for drug delivery purposes.

The Fate of Nanoparticles In Vivo and the Strategy of Designing Stealth Nanoparticle for Drug Delivery.

Nano-drug delivery systems (Nano-DDS) offer powerful advantages in drug delivery and targeted therapy for diseases. Compared to the traditional drug formulations, Nano-DDS can increase solubility, biocompatibility, and reduce off-targeted side effects of free drugs. However, they still have some disadvantages that pose a limitation in reaching their full potential in clinical use. Protein adsorption in blood, activation of the complement system, and subsequent sequestration by the mononuclear phagocyte system (MPS) consequently result in nanoparticles (NPs) to be rapidly cleared from circulation. Therefore, NPs have low drug delivery efficiency. So, it is important to develop stealth NPs for reducing bio-nano interaction. In this review, we first conclude the interaction between NPs and biological environments, such as blood proteins and MPS, and factors influencing each other. Next, we will summarize the new strategies to reduce NPs protein adsorption and uptake by the MPS based on current knowledge of the bio-nano interaction. Further directions will also be highlighted for the development of biomimetic stealth nano-delivery systems by combining targeted strategies for a better therapeutic effect.

Preparation and Characterization of Ginger Lipid-derived Nanoparticles for Colon-targeted siRNA Delivery.

Synthetic nanoparticle-based drug delivery system is widely known for its ability to increase the efficacy and specificity of loaded drugs, but it often suffers from relatively higher immunotoxicity and higher costs as compared to traditional drug formulations. Contrarily, plant-derived nanoparticles appear to be free from these limitations of synthetic nanoparticles; they are naturally occurring biocompatible vesicles that do not generate immunotoxicity and are easy to obtain. Additionally, lipids isolated from plant-derived nanoparticles have shown the capability of assembling themselves to spherical nano-sized liposomal particles. Herein, we employ lipids extracted from ginger-derived nanoparticles and load them with therapeutic siRNA (CD98-siRNA) to create CD98-siRNA/ginger-lipid nanoparticles. Characterization of the CD98-siRNA/ginger-lipid nanoparticles showed that they present a spherical shape, with a diameter of around 189.5 nm. The surface zeta potential of the nanoparticles varies from -18.1 to -18.4 mV. Furthermore, in recent research, the CD98-siRNA/ginger-lipid nanoparticles have shown specific colon targeting capability and excellent anti-inflammatory efficacy in a Dextran Sodium Sulfate (DSS) induced mouse model of colitis.

Cocos nucifera L. inflorescence extract: An effective hepatoprotective agent

The flowering inflorescence of Cocos nucifera, a main constituent of several traditional drug formulations was investigated with a view to study the effect of the acetone extract of C. nucifera inflorescence (CnAE) on acetaminophen-induced hepatotoxicity. The total phenol and flavonoid contents of the extract are found to be 222.6 µg gallic acid equivalent/g and 120.8 µg quercetin equivalent/g, respectively. The LD50 value was >5000 mg/kg b.w. The antioxidant activity was assessed using three methods, namely, 2,2’- diphenyl-1-picryl hydrazyl assay, 2,2’-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay and ferric reducing antioxidant power assay and the IC50 values were found to be 65.72, 66.94 and 89.84 μg/mL, respectively. Effect of CnAE (100, 200 and 400 mg/kg b.w.) and silymarin (100 mg/kg b.w.) against acetaminophen-induced liver toxicity was evaluated in Wistar rats. The study showed that CnAE pre-treated groups remarkably prevented the increase in serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase level and decrease in the level of liver superoxide dismutase, reduced glutathione, glutathione-S-transferase and glutathione peroxidise. The extract also suppressed the elevated level of malondialdehyde. The biochemical determinations supported the histopathological examination and blood parameter findings. The findings of our study indicated that the phenolic-rich CnAE could be an interesting alternative candidate against acetaminophen-induced hepato-toxicity and associated oxidative stress.

Protein-Polymer Delivery: Chemistry from the Cold Chain to the Clinic.

Drug delivery is commonly thought of as the performance of a drug in vivo. Rather, the process of drug delivery can comprise of the journey of the drug from manufacturer to clinic, clinic to patient, and patient to disease. Each step of the journey includes hurdles that must be overcome for the therapeutic to be successful. Recent developments in proteinaceous therapeutics have made the successful completion of this journey even more important because of the relatively fragile nature of proteins in a drug delivery context. Polymers have been demonstrated to be an effective complement to proteinaceous therapeutics throughout this journey owing to their flexibility in design and function. During transit from manufacturer to clinic, the proteinaceous drug is threatened by denaturation at elevated temperatures. Polymers can help improve the thermal stability of the drug at ambient shipping conditions, thereby reducing the need for an expensive cold chain to preserve its bioactivity. Upon arrival at the clinic, the drug must be reconstituted into a suitable formulation that can be introduced into the patient. Unfortunately, traditional drug formulations relying on oral administration are generally not suitable for proteinaceous drugs owing to the hostile environment of the stomach. Other traditional methods of drug administration-like hypodermic injections-frequently suffer from low patient compliance. Polymers have been explored to design drug formulations suitable for alternative methods of administration. Upon entry into the body, proteinaceous drugs are at risk for identification, destruction, and excretion by the immune system. Polymers can help drugs reprogram immune system response and, in some cases, elicit a synergistic immune response. The next phase of research on protein-polymer-based therapeutics encourages a holistic effort to design systems that can survive each stage of the drug delivery journey.

Nanoparticle-based drug delivery systems: What can they really do in vivo?

In the past few decades, there has been explosive growth in the construction of nanoparticle-based drug delivery systems (NDDSs), namely nanomedicines, owing to their unique properties compared with traditional drug formulations. However, because of a variety of challenges, few nanomedicines are on sale in the market or undergoing clinical trial at present. Thus, it is essential to look back and re-evaluate what these NDDSs can really do in vivo, why nanomedicines are regarded as potential candidates for next-generation drugs, and what the future of nanomedicine is. Here, we focus mainly on the properties of NDDSs that extend blood circulation, enhance penetration into deep tumor tissue, enable controllable release of the payload into the cytoplasm, and overcome multi-drug resistance. We further discuss how to promote the translation of nanomedicines into reality. This review may help to identify the functions of NDDSs that are really necessary before they are designed and to reduce the gap between basic research and clinical application.

Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety

Chemotherapy plays an irreplaceable role in the treatment of various malignant tumors today. The traditional drug formulations lack of selectivity, cause serious damage to normal tissues, and can’t achieve a desired therapeutic efficacy. For this situation, a facilely prepared reduction-responsive polypeptide nanogel was employed for targeting intracellular delivery of antitumor drug in this study. Doxorubicin (DOX) as a model drug was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency (DLE) of 56.8wt.%. The loading nanogel, i.e., NG/DOX, exhibited a medium hydrodynamic radius of 56.1±3.5nm, glutathione-accelerated DOX release, and efficient cellular uptake and proliferation inhibition. Moreover, NG/DOX exhibited upregulated intratumoral accumulation and improved antitumor efficacy toward HepG2 hepatoma-xenografted BALB/c nude mouse model compared with free drug. The enhanced tumor suppression of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was systematically demonstrated by the variation detection of body weight, histopathological assay, levels of bone marrow cell micronucleus rate (BMMR) and white blood cells (WBCs), and detection of clinical parameters in corresponding organs and serum. With controllable large-scale preparation and fascinating properties in vitro and in vivo, the reduction-responsive polypeptide nanogel is revealed to exhibit great potential for on-demand intracellular delivery of antitumor drugs, and shows a good prospect for clinical chemotherapy. Statement of SignificanceThe traditional drug formulations lack of selectivity, cause serious damage to normal tissues, and can’t achieve a desired therapeutic effect. For this situation, a facilely prepared reduction-responsive polypeptide nanogel is employed for targeting intracellular delivery of antitumor drug in this study. The laden nanogel keeps structural integrity and less drug release in the circulatory system after intravenous injection, releases the payload triggered by the intracellular high concentration of GSH, and exhibits the excellent tumor inhibition and security in vivo. Furthermore, the other hydrophobic antitumor drugs can also be on-demand delivered by the smart nanogel. All of the above advantages confirm the bright prospect of reduction-responsive nanogel on the road of malignancy chemotherapy.

Biodegradable In Situ Gel-Forming Controlled Drug Delivery System Based on Thermosensitive Poly(ε-caprolactone)-Poly(ethylene glycol)-Poly(ε-caprolactone) Hydrogel.

Traditional drug delivery systems which are based on multiple dosing regimens usually pose many disadvantages such as poor compliance of patients and drug plasma level variation. To overcome the obstacles of traditional drug formulations, novel drug delivery system PCL-PEG-PCL hydrogels have been purposed in this study. Copolymers were synthesized by rapid microwave-assisted and conventional synthesis methods. Polymer characterizations were done using gel permeation chromatography and 1H-NMR. Phase transition behavior was evaluated by inverting tube method and in vitro drug release profile was determined using naltrexone hydrochloride and vitamin B12 as drug models. The results indicated that loaded drug structure and copolymer concentration play critical roles in release profile of drugs from these hydrogels. This study also confirmed that synthesis of copolymer using microwave is the most effective method for synthesis of this kind of copolymer.

(281) Abuse-deterrent properties and pharmacokinetics of a novel sustained release formulation of oxycodone for the treatment of moderate to severe pain

Oxycodone and other opiate agonists provide effective pain relief when administered as intended. Currently marketed sustained release formulations are subject to misuse, since the time-release mechanism can be destroyed by chewing or crushing the formulation, making the drug immediately available. Crushed or chewed dosage forms are commonly self-administered by abusers orally, intranasally or by IV injection, resulting in a “high.” COL-003 is a novel formulation of oxycodone, utilizing the DETERX technology platform, designed to be more resistant to tampering and misuse than traditional drug formulations.