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Posted: September 13th, 2023
P750 LOGBOOK 5 STUDENT ID : 6469969
To treat cataract, cystine is applied topically in the form of eye drops. The factors that reduce cystine bioavailability are,
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Tear film :- Topically applied drugs will first encounter tear film and it is considered as first protective structure.
Nasolacrimal drainage system :- After the application cystine eye drops tear fluid turnover doubles it is called as washout effect. Due to pH and foreign body sensation reflex tearing will occur.
Cornea :- It is the main mechanical barrier. Due to its sandwich like structure drugs with molecular weight less than 5 K Da and partition coefficient of 10 to 100 can pass through it. Cornea is composed of three layers, the outermost layer is epithelium which is lipophilic in nature, middle layer is stroma which is hydrophilic in nature and innermost layer is endothelium which is lipophilic in nature.
FORMULATION PARAMETERS : – The formulation parameters to be considered in formulating a topical cystine eye drops are,
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FORMULATION APPROACH : – Colloidal ocular delivery systems like micro emulsions are used to deliver the antioxidant cystine in the form of topical eye drops.
Micro emulsions : –
Antisense oligonucleotides (As ODN) : –
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Delivery route : – I would like to choose intra-vitreous delivery route because, periocular injections of antisense oligonucleotides is responsible for poor stability and it is difficult for antisense oligonucleotides to penetrate through the cells.
Intra-vitreous injection : – It is the injection of antisense oligonucleotides into the vitreous with the help of a needle. In the treatment of many of the ocular diseases intra-vitreous administration of drugs is used.
Advantages of intra-vitreous injection :
Disadvantages of intra-vitreous injection :
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FORMULATION PARAMETERS :-
Chemical modification : – chemical modification of antisense oligonucleotides leads to increased or decreased solubility, stability etc..
FORMULATION APPROACH :-
To prevent antisense oligonucleotides (As ODN) from enzymatic degradation and to improve the cellular uptake a variety of formulation approaches have been put forward. They are, liposomes, nanoparticles, peptides, dendrimers, and physical methods. Among these i would like to choose multi functional dendrimer carriers.
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Dendrimer carriers :-
Dendrimers are branched molecules and spherical in nature. Dendrimers are divided into low molecular weight and high molecular weight species. The properties of dendrimers depends on the functional groups at their molecular level. Dendrimers are cationic in nature and possess positive charge on it.
Antisense oligonucleotides shows its therapeutic effect at cytoplasmic level and these antisense oligonucleotides are anionic in nature and possess negative charge. During the formulation, dendrimer undergoes complexation and condensation with antisense oligonucleotides. The functional groups present at the molecular level are.
TAT peptide is derived from human immunodeficiency virus and it acts as a cell penetrating peptide. TAT helps in cellular uptake of dendrimer antisense oligonucleotide complex.
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Dendrimer- antisense oligonucleotide complex binds to the cell membrane than enters in to the cell through endocytosis. These fusogenic peptide helps in endisomal escape. Influenza virus hemagglutinin subunit-2 is a fusogenic peptide.
This functional group helps in improving permeability and stability. Example, C14
Disadvantage of dendrimer carrier : – cytotoxicity increases due to the presence of cell penetrating peptides and fusogenic peptides
REFERENCE :-
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