SNAC for Enhanced Oral Bioavailability: An Updated Review.

The delivery of proteins and peptides via an oral route poses numerous challenges to improve the oral bioavailability and patient compliance. To overcome these challenges, as well as to improve the permeation of proteins and peptides via intestinal mucosa, several chemicals have been studied such as surfactants, fatty acids, bile salts, pH modifiers, and chelating agents, amongst these medium chain fatty acid like C10 (sodium caprate) and Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) and its derivatives that have been well studied from a clinical perspective. This current review enumerates the challenges involved in protein and peptide delivery via the oral route, i.e., non-invasive routes of protein and peptide administration. This review also covers the chemistry behind SNAC and toxicity as well as mechanisms to enhance the oral delivery of clinically proven molecules like simaglutide and other small molecules under clinical development, as well as other permeation enhancers for efficient delivery of proteins and peptides.

Computational and experimental therapeutic efficacy analysis of andrographolide phospholipid complex self-assembled nanoparticles against Neuro2a cells.

BACKGROUND: Neuroblastoma is one of the most common malignancies in childhood, accounts for approximately 7% of all malignancies. Andrographolide (AN) inhibits cancer cells progression via multiple pathways like cell cycle arrest, mitochondrial apoptosis, NF-κß inhibition, and antiangiogenesis mechanism. Despite multiple advantages, application of AN is very limited due to its low aqueous solubility (6.39 ± 0.47 µg/mL), high lipophilicity (log P âˆ¼ 2.632 ± 0.135), and reduced stability owing to pH sensitive lactone ring. OBJECTIVES AND RESULTS: In present investigation, a molecular complex of AN with soya-L-α-phosphatidyl choline (SPC) was synthesized as ANSPC and characterized by FT-IR and1H NMR spectroscopy. Spectral and molecular simulation techniques confirmed the intermolecular interactions between the 14-OH group of AN and the N+(CH3)3part of SPC. In addition, molecular dynamics (MD) simulation was used to determine the degree of interaction between various proteins such as TNF-α, caspase-3, and Bcl-2. Later, ANSPC complex was transformed in to self-assembled soft nanoparticles of size 201.8 ± 1.48 nm with PDI of 0.092 ± 0.004 and zeta potential of -21.7 ± 0.85 mV. The IC50 offree AN (8.319 µg/mL) and the self-assembled soft ANSPC nanoparticles (3.406 µg/mL âˆ¼ 1.2 µg of AN) against Neuro2a cells was estimated with significant (P < 0.05) difference. Interestingly, the self-assembled soft ANSPC nanoparticles showed better endocytosis compared to free AN in Neuro2a cells. In-vitrobiological assays confirmed that self-assembled soft ANSPC nanoparticles induces apoptosis in Neuro2a cells by declining the MMP (Δψm) and increasing the ROS generation. CONCLUSION: Self-assembled soft ANSPC nanoparticles warrant further in-depth antitumor study in xenograft model of neuroblastoma to establish the anticancer potential.

Freeze-drying for the preservation of immunoengineering products.

Immunoengineering technologies harness the power of immune system modulators such as monoclonal antibodies, cytokines, and vaccines to treat myriad diseases. Immunoengineering innovations have showed great promise in various practices including oncology, infectious disease, autoimmune diseases, and transplantation. Despite the countless successes, the majority of immunoengineering products contain active moieties that are prone to instability. The current review aims to feature freeze-drying as a robust and scalable solution to the inherent stability challenges in immunoengineering products by preventing the active moiety from degradation. Furthermore, this review describes the stability issues related to immunoengineering products and the utility of the lyophilization process to preserve the integrity and efficacy of immunoengineering tools ranging from biologics to nanoparticle-based vaccines. The concept of the freeze-drying process is described highlighting the quality by design (QbD) for robust process optimization. Case studies of lyophilized immunoengineering technologies and relevant clinical studies using immunoengineering products are discussed.

Stability characterization for pharmaceutical liposome product development with focus on regulatory considerations: An update.

Liposomes have several advantages, such as the ability to be employed as a carrier/vehicle for a variety of drug molecules and at the same time they are safe and biodegradable. In the recent times, compared to other delivery systems, liposomes have been one of the most well-established and commercializing drug products of new drug delivery methods for majority of therapeutic applications. On the other hand, it has several limitations, particularly in terms of stability, which impedes product development and performance. In this review, we reviewed all the potential instabilities (physical, chemical, and biological) that a formulation development scientist confronts throughout the development of liposomal formulations as along with the ways to overcome these challenges. We have also discussed the effect of microbiological contamination on liposomal formulations with a focus on the use of sterilization methods used to improve the stability. Finally, we have reviewed quality control techniques and regulatory considerations recommended by the agencies (USFDA and MHLW) for liposome drug product development.

Armamentarium of Cryoprotectants in Peptide Vaccines: Mechanistic Insight, Challenges, Opportunities and Future Prospects.

Vaccines are designed to leverage the immune system and produce long-lasting protection against specific diseases. Peptide vaccines are regarded as safe and effective way of circumventing problems such as mild allergic reactions associated with conventional vaccines. The biggest challenges associated with formulation of peptide vaccines are stability issues and conformational changes which lead to destruction of their activity when exposed to lyophilization process that may act as stressors. Lyophilization process is aimed at removal of water which involves freezing, primary drying and secondary drying. To safeguard the peptide molecules from such stresses, cryoprotectants are used to offer them viability and structural stability. This paper is an attempt to understand the physicochemical properties of peptide vaccines, mechanism of cryoprotection under the shed of water replacement, water substitution theory and cation-pi interaction theory of amino acids which aims at shielding the peptide from external environment by formation of hydrogen bonds, covalent bonds or cation-pi interaction between cryoprotectant and peptide followed by selection criteria of cryoprotectants and their utility in peptide vaccines development along with challenges and opportunities.

Self healing hydrogels: A new paradigm immunoadjuvant for delivering peptide vaccine.

Immunoadjuvants are added to the vaccines in order to enhance and prolong the antigen specific immune responses when used in consolidation with specific vaccine antigens. This permits the use of antigen in lower quantity and allows immunization protocols practicing the vaccine with smaller doses. Self-healing hydrogels have the ability to heal the damages instinctively and reinstate its framework to ordinariness in absence of external stimuli. Moreover, self-healing hydrogel having various properties such as shear-thinning and reversible sol-gel transformation properties allow it to be readily delivered via injection. Therefore, in the present review, self- healing hydrogel is projected to be used as a carrier for sustained release of peptide and as an analogous to immunoadjuvant. The sustained release property of self-healing hydrogel may be credited to the changes in the structure in response to internal or external stimuli. In addition to the huge potential of stimuli-responsive self-healing hydrogels, they also exhibit good mechanical properties. These properties make self-healing hydrogel as a smart material in delivering the vaccines. Moreover, we have also summarized diverse range of physical and chemical reactions reported for the scale-up of self-healing hydrogels in this review.