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1.
Int J Pharm ; 646: 123446, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37751787

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevailing bacterial pathogen linked to superficial skin and soft tissue infections (SSTIs). Rifampicin (RIF), a potent antibiotic against systemic and localised staphylococcal infections, faces limitations due to its low solubility. This constraint hampers its therapeutic potential for MRSA-induced SSTIs. To address this, an advanced liposomal system was designed for efficient dermal RIF delivery. Rifampicin-loaded liposomes (LipoRIF) were embedded within polymeric dissolving microneedles (DMNs) to enable targeted intradermal drug delivery. A robust Design of Experiment (DoE) methodology guided the systematic preparation and optimisation of LipoRIF formulations. The optimal LipoRIF formulation integrated within polymeric DMNs. These LipoRIF-DMNs exhibited favourable mechanical properties and effective skin insertion characteristics. Notably, in vitro assays on skin deposition unveiled a transformative result - the DMN platform significantly enhanced LipoRIF deposition within the skin, surpassing LipoRIF dispersion alone. Moreover, LipoRIF-DMNs displayed minimal cytotoxicity toward cells. Encouragingly, rigorous in vitro antimicrobial evaluations demonstrated LipoRIF-DMNs' capacity to inhibit MRSA growth compared to the control group. LipoRIF-DMNs propose a potentially enhanced, minimally invasive approach to effectively manage SSTIs and superficial skin ailments stemming from MRSA infections.

2.
Adv Drug Deliv Rev ; 200: 115003, 2023 09.
Article in English | MEDLINE | ID: mdl-37422267

ABSTRACT

Polymeric in situ forming depots have emerged as highly promising drug delivery systems for long-acting applications. Their effectiveness is attributed to essential characteristics such as biocompatibility, biodegradability, and the ability to form a stable gel or solid upon injection. Moreover, they provide added versatility by complementing existing polymeric drug delivery systems like micro- and nanoparticles. The formulation's low viscosity facilitates manufacturing unit operations and enhances delivery efficiency, as it can be easily administered via hypodermic needles. The release mechanism of drugs from these systems can be predetermined using various functional polymers. To enable unique depot design, numerous strategies involving physiological and chemical stimuli have been explored. Important assessment criteria for in situ forming depots include biocompatibility, gel strength and syringeability, texture, biodegradation, release profile, and sterility. This review focuses on the fabrication approaches, key evaluation parameters, and pharmaceutical applications of in situ forming depots, considering perspectives from academia and industry. Additionally, insights about the future prospects of this technology are discussed.


Subject(s)
Drug Delivery Systems , Nanoparticles , Humans , Delayed-Action Preparations , Polymers , Injections
3.
Drug Discov Today ; 26(11): 2619-2636, 2021 11.
Article in English | MEDLINE | ID: mdl-34332100

ABSTRACT

Unlike conventional Coronavirus 2019 (COVID-19) vaccines, intranasal vaccines display a superior advantage because the nasal mucosa is often the initial site of infection. Preclinical and clinical studies concerning intranasal immunization elicit high neutralizing antibody generation and mucosal IgA and T cell responses that avoid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both; the upper and lower respiratory tract. A nasal formulation is non-invasive with high appeal to patients. Intranasal vaccines enable self-administration and can be designed to survive at ambient temperatures, thereby simplifying logistical aspects of transport and storage. In this review, we provide an overview of nasal vaccines with a focus on formulation development as well as ongoing preclinical and clinical studies for SARS-CoV-2 intranasal vaccine products.


Subject(s)
Administration, Intranasal , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Drug Development , Adjuvants, Vaccine , Antigen-Presenting Cells/immunology , Drug Delivery Systems , Humans , Hydrogen-Ion Concentration , Immunity, Mucosal/immunology , Immunogenicity, Vaccine , Immunoglobulin A/immunology , SARS-CoV-2 , T-Lymphocytes/immunology
4.
Drug Discov Today ; 26(6): 1510-1520, 2021 06.
Article in English | MEDLINE | ID: mdl-33684525

ABSTRACT

Proteins and peptides are amongst the most sought-after biomolecules because of their exceptional potential to cater to a vast range of diseases. Although widely studied and researched, the oral delivery of these biomolecules remains a challenge. Alongside formulation strategies, approaches to overcome the inherent barriers for peptide absorption are being designed at the molecular level to establish a sound rationale and to achieve higher bioavailability. Computer-aided drug design (CADD) is a modern in silico approach for developing successful bio-formulations. CADD enables intricate study of the biomolecules in conjunction with their target sites or receptors at the molecular level. Knowledge of the molecular interactions of proteins and peptides makes way for the pre-screening of suitable formulation components and facilitates their delivery.


Subject(s)
Drug Design , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Oral , Animals , Biological Availability , Computer Simulation , Drug Delivery Systems , Humans , Peptides/pharmacokinetics , Proteins/pharmacokinetics
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